Spirocyclic KRAS inhibitors for treating disease

Abstract

The present disclosure relates to spirocyclic compounds targeting KRAS, pharmaceutical compositions containing the compounds, and methods of using such compounds to treat disease, such as cancer.

Description

SPIROCYCLIC KRAS INHIBITORS FOR TREATING DISEASE RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 670,415, filed July 12, 2024, U.S. Provisional Application No.63 / 687,146, filed August 26, 2024, U.S. Provisional Application No. 63 / 760,454, filed February 19, 2025, and U.S. Provisional Application No. 63 / 836,888, filed July 1, 2025, the entire disclosures of all of which are incorporated herein by reference. TECHNICAL FIELD

[0002] The present disclosure relates to spirocyclic compounds targeting KRAS, pharmaceutical compositions containing the compounds, and methods of using such compounds to treat disease, such as cancer. BACKGROUND

[0003] Ras is a GTP-binding protein and regulates many important physiologic processes within a cell, such as cell cycle progression, survival, apoptosis, etc. H-Ras, K-Ras, and N- Ras are the main members of Ras superfamily, which are tightly regulated by factors that switch on / off the GTPase activity. Somatic mutations at codons 12, 13, and 61 in the RAS genes are associated with about 16% of all human cancers and KRAS is the most frequently mutated RAS isoform, accounting for 85% of all RAS-related cancers (Prior I. A. et al, A comprehensive survey of Ras mutations in cancer. Cancer Res. 2012, 72, 2457−2467), including 86-96% in pancreatic cancers, 40-50% in colorectal cancers, and 27-39% in lung adenocarcinomas (Kessler D. et al. Drugging an undruggable pocket on KRAS Proc Natl Acad Sci U S A.2019, 116(32):15823-15829). Mutated RAS is locked in the constitutively activated GTP bound state and facilitates enhanced Ras signaling in cancer cells.

[0004] Direct targeting of mutant KRAS has previously proven challenging because of its high affinity for nucleotide and the lack of tractable binding pockets for small-molecule inhibitors. Recent successful inhibition of the KRAS G12C mutant by covalent chemical modifiers sotorasib and adagrasib (Stower K, KRAS inhibitors at last, Nature Medicine 2020, 26, 1804) in KRAS G12C mutated lung cancer patients has shed lights on targeting KRAS mutants for therapeutic invention. However, inhibitors targeting KRAS mutants without covalent formation at KRAS G12C are still absent. The increased understanding of structural elements of the KRAS switch II pocket made it possible to design KRAS inhibitors selective for different mutant variants. MRTX1133 has been reported as potent and highly selective noncovalent KRAS G12D inhibitor (Wang X. et al, Identification of MRTX1133, anoncovalent, potent, and selective KRASG12Dinhibitor, J. Med. Chem.2022, 65: 3123–3133). However, intraperitoneal injection of MRTX1133 was required to achieve sufficient plasma exposure and demonstrate drug efficacy in mice. This suggests MRTX1133 may have poor bioavailability.

[0005] Therefore, there is unmet medical need to develop noncovalent KRAS inhibitors thatcan selectively target KRAS mutants such as KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12R, KRAS G12S, KRAS G13C, and KRAS G13D with good in vivo efficacy, safety, and predicted human oral pharmacokinetic profile for treating patients with KRAS mutant cancers. SUMMARY

[0006] In one aspect, the disclosure relates to a compound of the formula I,I or a pharmaceutically acceptable salt thereof, wherein ring A is 5- or 6-membered heteroaryl; ring B is a 5- to 10-membered heteroaryl or a 7- to 11-membered heterobicyclyl; X is a bond, -O-, -S-, or -NR7-; each of X1and X3is independently an -O-, -S-, -S(O)2-, or -CH2-, X2is a bond, -O-, -S-, -S(O)2-, or -CH2-, provided that no more than one of X1, X2, and X3is a -O-, -S-, or -S(O)2-; Y is -O-, -S-, -S(O)-, -S(O)2-, -NH-, -CH2-, -CH2CH2-, -OCH2-, -CH2O-, -SCH2-, -CH2S-, -S(O)CH2-, -CH2S(O)-, -S(O)2CH2-, -CH2S(O)2-, -NHCH2-, or -CH2NH-; each R1, when present, when bonded to carbon is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb,-C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; each R1, when present, when bonded to nitrogen is independently deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -C(O)Ra, -C(O)ORa, or -C(O)NRaRb; or two R1, when present, taken together with the atoms to which they are attached, combine to form a C3C6cycloalkyl, 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; or an R1and an R2, when present, taken together with the atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, or a 5- to 10-membered heteroaryl; or an R1and R7, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), and 4- to 10- membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each R2, when present, when bonded to carbon is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; each R2, when present, when bonded to nitrogen is independently deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, -C(O)Ra, -C(O)ORa, or -C(O)NRaRb; or two R2, when present, taken together with the atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; or an R2and an R3, whenpresent, taken together with the atoms to which they are attached, combine to form a C6-C8cycloalkyl or 6- to 8-membered heterocycloalkyl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl, C6-C8cycloalkyl, and 6- to 8-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each R3and R4, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -ORc, -OC(O)Rc, -OC(O)NRcRd, -OC(=NRc)NRcRd, -OS(O)Rc, -OS(O)2Rc, -OS(O)NRcRd, -OS(O)2NRcRd, -SRc, -S(O)Rc, -S(O)2Rc, -S(O)NRcRd, -S(O)2NRcRd, -NRcRd, -NRcC(O)Rd, -NRcC(O)ORd, -NRcC(O)NRcRd, -NRcC(=NRd)NRcRd, -NRcS(O)Rd, -NRcS(O)2Rd, -NRcS(O)NRcRd, -NRcS(O)2NRcRd, -C(O)Rc, -C(O)ORc, -C(O)NRcRd, -C(=NRc)NRcRd, -PRcRd, -P(O)RcRd, -P(O)2RcRd, -P(O)NRcRd, -P(O)2NRcRd, -P(O)ORc, -P(O)2ORc, -CN, or -NO2; or two R3or two R4, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6cycloalkyl or a 4- to 10-membered heterocycloalkyl; or two R3or two R4, when present, taken together with the carbon atom to which they are attached combine to form an oxo group or a C2-C6alkenyl group; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each R5, when present, is H, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, and 5- to 10-membered heteroaryl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf,-OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; R6is -C1-C6alkyl, -C2-C6alkenyl, -C2-C6alkynyl, -C3-C6cycloalkyl, 4- to 10- membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, or -C1-C6alkylene-(5- to 10- membered heteroaryl), wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10- membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and -C1-C6alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene- (C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; R7, when present, is H, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl- C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each Ra, Rb, Rc, Rd, Re, and Rfis independently selected from the group consisting of H, deuterium, C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and C1-C6alkylene-(5- to 10-membered heteroaryl); or two of Raand Rb, or Rcand Rd, or Reand Rf, taken together with the atom or atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl; or Reand Rftaken together with the carbon atom to which they are attached form an oxo groups or a C2-C6alkenyl; wherein each hydrogen atom in C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and C1-C6alkylene-(5- to 10-membered heteroaryl) is independently optionally substituted by deuterium, halogen, or Rg; each Rgis independently optionally substituted C1-C6alkyl, optionally substituted C3-C6cycloalkyl, optionally substituted 4- to 10-membered heterocycloalkyl, optionally substituted C6-C10aryl, optionally substituted 5- to 10-membered heteroaryl, -OH, -OC1-C6alkyl, -OC(O)C1-C6alkyl, -OC(O)N(H or C1-C6alkyl)2, -OS(O)C1-C6alkyl, -OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6alkyl)2, -OS(O)2N(H or C1-C6alkyl)2, -SC1-C6alkyl, -S(O)C1-C6alkyl, -S(O)2C1-C6alkyl, -S(O)N(H or C1-C6alkyl)2, -S(O)2N(H or C1-C6alkyl)2, -N(H or C1-C6alkyl)2, -N(C1-C6alkyl)C(O)-C1-C6alkyl, -N(C1-C6alkyl)C(O)OC1-C6alkyl, -N(C1-C6alkyl)C(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)C1-C6alkyl, -N(C1-C6alkyl)S(O)2C1-C6alkyl, -N(C1-C6alkyl)S(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)2N(H or C1-C6alkyl)2, -C(O)C1-C6alkyl, -C(O)OC1-C6alkyl, -C(O)N(H or C1-C6alkyl)2, -P(H or C1-C6alkyl)2, -P(O)(H or C1-C6alkyl)2, -P(O)2(H or C1-C6alkyl)2, -P(O)N(H or C1-C6alkyl)2, -P(O)2N(H or C1-C6alkyl)2, -P(O)OC1-C6alkyl, or -P(O)2OC1-C6alkyl,; m1 is 0, 1, or 2; m2 is 0, 1, or 2; m3 is 0 or 1; n1 is 0, 1, 2, 3, or 4; and n2 is 0, 1, 2, 3, or 4; provided that when ring B is a 6-membered heteroaryl, then: (i) Y is -O-, -S-, -S(O)-, -S(O)2-, -NH-, -OCH2-, -CH2O-, -SCH2-, -CH2S-, -NHCH2-, or -CH2NH-; or (ii) an R2and an R3, when present, taken together with the atoms to which they are attached, combine to form a C6-C8cycloalkyl or 6- to 8-membered heterocycloalkyl; or (iii) two R3, when present, taken together with the atom or atoms to which they are attached, combine to form a C4-C6cycloalkyl or 4- to 6-membered heterocycloalkyl; orĨiv) combinations thereof.

[0007] In another aspect, the disclosure provides a compound of the formula II,

[0008] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R5, R6, X, Y, m1, m2, m3, n1, and n2 are as described herein.

[0009] In another aspect, the disclosure provides a compound of the formula III,

[0010] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R6, X, Y, Y1, Y2, m1, m2, n1, and n2 are as described herein.

[0011] In another aspect, the disclosure provides a compound of the formula IV,

[0012] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R6, X, Y1, Y2, m1, m2, n1, and n2 are as described herein.

[0013] In another aspect, the disclosure provides a compound of the formula V,

[0014] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R3,R4, R6, X, Y,Y1, Y2, Z, Z1, Z2, Z3, n1, and n2 are as described herein.

[0015] In another aspect, the disclosure provides a compound of the formula VI,

[0016] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R3,R4, R6, X, Y,Y1, Y2, Z, Z1, Z2, Z3, n1, and n2 are as described herein.

[0017] In another aspect, the disclosure provides a compound of the formula VII,

[0018] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R5, R6, X, m1, m2, m3, n1, and n2 are as described herein.

[0019] In another aspect, the disclosure provides a compound of the formula VIII,

[0020] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R5, R6, X, m1, m2, m3, n1, and n2 are as described herein.

[0021] In another aspect, the disclosure provides a compound of the formula IX,

[0022] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R6, X, Y1, Y2, m1, m2, n1, and n2 are as described herein.

[0023] In another aspect, the disclosure provides a compound of the formula X,

[0024] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R6, X, Y1, Y2, m1, m2, n1, and n2 are as described herein.

[0025] In another aspect, the disclosure provides a compound of the formula XI,

[0026] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R3,R4, R6, X, Y1,Y2, Z, Z1, Z2, Z3, n1, and n2 are as described herein.

[0027] In another aspect, the disclosure provides a compound of the formula XII,

[0028] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R3,R4, R6, X, Y1,Y2, Z, Z1, Z2, Z3, n1, and n2 are as described herein. In certain embodiments, ring B is of the formula,,

[0029] wherein “ ” is a point of covalent attachment to ring A.

[0030] In certain embodiments of the above aspects, the compound of Formula (I)-(XXVI) isa compound selected from those species described or exemplified in the detailed description below.

[0031] In further aspects, the disclosure relates to a pharmaceutical composition comprising atleast one compound of Formula (I)-(XXVI) or a pharmaceutically acceptable salt thereof. Pharmaceutical compositions according to the disclosure may further comprise a pharmaceutically acceptable excipient.

[0032] In further aspects, the disclosure relates to a compound of Formula (I)-(XXVI), or apharmaceutically acceptable salt thereof, for use as a medicament.

[0033] In further aspects, the disclosure relates to a method of treating disease, such as cancercomprising administering to a subject in need of such treatment an effective amount of at least one compound of Formula (I)-(XXVI), or a pharmaceutically acceptable salt thereof.

[0034] In further aspects, the disclosure relates to use of a compound of Formula (I)-(XXVI),or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for the treatment of disease, such as cancer, and the use of such compounds and salts for treatment of such diseases.

[0035] In further aspects, the disclosure relates to a method of inhibiting a Ras, such as K-Ras,comprising contacting a cell comprising one or more of Ras with an effective amount of atleast one compound of Formula (I)-(XXVI), or a pharmaceutically acceptable salt thereof, and / or with at least one pharmaceutical composition of the disclosure, wherein the contacting is in vitro, ex vivo, or in vivo.

[0036] Additional embodiments, features, and advantages of the disclosure will be apparentfrom the following detailed description and through practice of the disclosure. The compounds of the present disclosure can be described as embodiments in any of the following enumerated clauses. It will be understood that any of the embodiments described herein can be used in connection with any other embodiments described herein to the extent that the embodiments do not contradict one another.

[0037] 1. A compound of the formula I, an isotopically labeled form thereof, or apharmaceutically acceptable salt thereof,

[0038] wherein

[0039] ring A is 5- or 6-membered heteroaryl;

[0040] ring B is a 5- to 10-membered heteroaryl or a 7- to 11-membered heterobicyclyl;

[0041] X is a bond, -O-, -S-, or -NR7-;

[0042] each of X1 and X3 is independently an -O-, -S-, -S(O)2-, or -CH2-, X2 is a bond, -O-,-S-, -S(O)2-, or -CH2-, provided that no more than one of X1, X2, and X3is a -O-, -S-, or -S(O)2- ;

[0043] Y is -O-, -S-, -S(O)-, -S(O)2-, -NH-, -CH2-, -CH2CH2-, -OCH2-, -CH2O-, -SCH2-,-CH2S-, -S(O)CH2-, -CH2S(O)-, -S(O)2CH2-, -CH2S(O)2-, -NHCH2-, or -CH2NH-;

[0044] eachR1, when present, when bonded to carbon is independently deuterium, halogen,C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, - P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; each R1, when present, when bonded to nitrogen is independently deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -C(O)Ra, -C(O)ORa, or -C(O)NRaRb; or two R1, when present, taken together with the atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; or an R1and an R2, when present, taken together with the atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, or a 5- to 10-membered heteroaryl; or an R1and R7, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), and 4- to 10- membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1- C6alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl- C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, - OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0045] each R2, when present, when bonded to carbon is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; each R2, when present, when bonded to nitrogen is independently deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, -C(O)Ra, -C(O)ORa, or -C(O)NRaRb; or two R2, when present, taken together with the atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; or an R2and an R3, whenpresent, taken together with the atoms to which they are attached, combine to form a C6-C8cycloalkyl or 6- to 8-membered heterocycloalkyl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl, C6-C8cycloalkyl, and 6- to 8-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, - Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0046] each R3and R4, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -ORc, -OC(O)Rc, -OC(O)NRcRd, -OC(=NRc)NRcRd, -OS(O)Rc, -OS(O)2Rc, -OS(O)NRcRd, -OS(O)2NRcRd, -SRc, -S(O)Rc, -S(O)2Rc, -S(O)NRcRd, -S(O)2NRcRd, -NRcRd, -NRcC(O)Rd, -NRcC(O)ORd, -NRcC(O)NRcRd, -NRcC(=NRd)NRcRd, -NRcS(O)Rd, -NRcS(O)2Rd, -NRcS(O)NRcRd, -NRcS(O)2NRcRd, -C(O)Rc, -C(O)ORc, -C(O)NRcRd, -C(=NRc)NRcRd, -PRcRd, -P(O)RcRd, -P(O)2RcRd, -P(O)NRcRd, -P(O)2NRcRd, -P(O)ORc, -P(O)2ORc, -CN, or -NO2; or two R3or two R4, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6cycloalkyl or a 4- to 10-membered heterocycloalkyl; or two R3or two R4, when present, taken together with the carbon atom to which they are attached combine to form an oxo group or a C2-C6alkenyl group; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1- C6alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, - OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, - NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0047] each R5, when present, is H, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, and 5- to 10-membered heteroaryl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0048] R6is -C1-C6alkyl, -C2-C6alkenyl, -C2-C6alkynyl, -C3-C6cycloalkyl, 4- to 10- membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, or -C1-C6alkylene-(5- to 10- membered heteroaryl), wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10- membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and -C1-C6alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), - OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10- membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0049] R7, when present, is H, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1- C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkylC(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -- OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, - NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, - NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, - P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2;

[0050] each Ra, Rb, Rc, Rd, Re, and Rfis independently selected from the group consisting of H, deuterium, C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and C1-C6alkylene-(5- to 10-membered heteroaryl); or two of Raand Rb, or Rcand Rd, or Reand Rf, taken together with the atom or atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl; or Reand Rftaken together with the carbon atom to which they are attached form an oxo groups or a C2-C6alkenyl; wherein each hydrogen atom in C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and C1-C6alkylene-(5- to 10-membered heteroaryl) is independently optionally substituted by deuterium, halogen, or Rg;

[0051] each Rgis independently optionally substituted C1-C6alkyl, optionally substituted C3-C6cycloalkyl, optionally substituted 4- to 10-membered heterocycloalkyl, optionally substituted C6-C10aryl, optionally substituted 5- to 10-membered heteroaryl, -OH, -OC1-C6alkyl, -OC(O)C1-C6alkyl, -OC(O)N(H or C1-C6alkyl)2, -OS(O)C1-C6alkyl, -OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6alkyl)2, -OS(O)2N(H or C1-C6alkyl)2, -SC1-C6alkyl, -S(O)C1-C6alkyl, -S(O)2C1-C6alkyl, -S(O)N(H or C1-C6alkyl)2, -S(O)2N(H or C1-C6alkyl)2, -N(H or C1- C6alkyl)2, -N(C1-C6alkyl)C(O)-C1-C6alkyl, -N(C1-C6alkyl)C(O)OC1-C6alkyl, -N(C1-C6alkyl)C(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)C1-C6alkyl, -N(C1-C6alkyl)S(O)2C1-C6alkyl, -N(C1-C6alkyl)S(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)2N(H or C1-C6alkyl)2, - C(O)C1-C6alkyl, -C(O)OC1-C6alkyl, -C(O)N(H or C1-C6alkyl)2, -P(H or C1-C6alkyl)2, - P(O)(H or C1-C6alkyl)2, -P(O)2(H or C1-C6alkyl)2, -P(O)N(H or C1-C6alkyl)2, -P(O)2N(H or C1-C6alkyl)2, -P(O)OC1-C6alkyl, or -P(O)2OC1-C6alkyl;

[0052] m1 is 0, 1, or 2;

[0053] m2 is 0, 1, or 2;

[0054] m3 is 0 or 1;

[0055] n1 is 0, 1, 2, 3, or 4; and

[0056] n2 is 0, 1, 2, 3, or 4;

[0057] provided that when ring B is a 6-membered heteroaryl, then:

[0058] (i) Y is -O-, -S-, -S(O)-, -S(O)2-, -NH-, -OCH2-, -CH2O-, -SCH2-, -CH2S-, -NHCH2-, or -CH2NH-; or

[0059] (ii) an R2and an R3, when present, taken together with the atoms to which they are attached, combine to form a C6-C8cycloalkyl or 6- to 8-membered heterocycloalkyl; or

[0060] (iii) two R3, when present, taken together with the atom or atoms to which they are attached, combine to form a C4-C6cycloalkyl or 4- to 6-membered heterocycloalkyl; or

[0061] (iv) combinations thereof.

[0062] 2. The compound of clause 1, an isotopically labeled form thereof, or apharmaceutically acceptable salt thereof, having the formula II.

[0063] 3. The compound of clause 1, an isotopically labeled form thereof, or apharmaceutically acceptable salt thereof, having the formula III

[0064] wherein Y1 and Y2 are each independently N, O, S, CH, CR5, or C, provided that atleast one of Y1and Y2is N, O, or S and only one of Y1and Y2is O or S.

[0065] 4. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, having the formula IV

[0066] wherein Y1 and Y2 are each independently N, O, S, CH, or C, provided that at least oneof Y1and Y2is N, O, or S and only one of Y1and Y2is O or S.

[0067] 5. The compound of clause 1 or 3, an isotopically labeled form thereof, or apharmaceutically acceptable salt thereof, having the formula V

[0068] wherein Y1 and Y2 are each independently N, O, S, CH, or C, provided that at least oneof Y1and Y2is N, O, or S and only one of Y1and Y2is O or S, each of Z and Z1is independently N, CH, or CR1, and each of Z2and Z3is independently N, CH, or CR2.

[0069] 6. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, having the formula VI

[0070] wherein Y1 and Y2 are each independently N, O, S, CH, or C, provided that at least oneof Y1and Y2is N, O, or S and only one of Y1and Y2is O or S, each of Z and Z1is independently N, CH, or CR1, and each of Z2and Z3is independently N, CH, or CR2.

[0071] 7. The compound of clause 1, an isotopically labeled form thereof, or apharmaceutically acceptable salt thereof, having the formula VII

[0072] 8. The compound of clause 1 or 2, an isotopically labeled form thereof, or apharmaceutically acceptable salt thereof, having the formula VIII

[0073] 9. The compound of clause 1, 3, or 7, an isotopically labeled form thereof, or apharmaceutically acceptable salt thereof, having the formula IX

[0074] 10. The compound of any one of clauses 1 to 4, or 7 to 9, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, having the formula X

[0075] 11. The compound of any one of clauses 1, 3, 5, 7, or 9, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, having the formula XI

[0076] 12. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, having the formula XII

[0077] 13. The compound of clause 1, an isotopically labeled form thereof, or apharmaceutically acceptable salt thereof, wherein ring B is a 5- to 10-membered heteroaryl.

[0078] 14. The compound of clause 1 or 13, an isotopically labeled form thereof, or apharmaceutically acceptable salt thereof, wherein ring B is a 6-membered monocyclic heteroaryl.

[0079] 15. The compound of clause 1 or 13, an isotopically labeled form thereof, or apharmaceutically acceptable salt thereof, wherein ring B is an 8- to 10-membered bicyclic heteroaryl.

[0080] 16. The compound of clause 1, an isotopically labeled form thereof, or apharmaceutically acceptable salt thereof, wherein ring B is a 7- to 11-membered heterobicyclyl.

[0081] 17. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein ring B is of the formula,,

[0082] wherein “” is a point of covalent attachment to ring A.

[0083] 18. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula , ,

[0084] wherein “” is a point of covalent attachment to ring A.

[0085] 19. The compound of any one of clauses 1, 13, 15, or 16, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, having the formula XIII

[0086] wherein each of Z, Z2, Z3, Z5, and Z6is independently N, CH, CR1, or CR2, Z1is N, C, CH, CR1, or CR2, and Z4is C or N.

[0087] 20. The compound of any one of clauses 1, 13, 15, or 16, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula XIV

[0088] 21. The compound of any one of clauses 1, 13, 15, or 16, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, having the formula XV

[0089] 22. The compound of any one of clauses 1, 13, 15, or 16, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, having the formula XVI

[0090] 23. The compound of any one of clauses 1, 13, 15, or 16, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, having the formula XVII(XVII).

[0091] 24. The compound of any one of clauses 1, 13, 15, or 16, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, having the formula XVIII(XVIII).

[0092] 25. The compound of any one of clauses 1 to 13, 15 to 17, or 19 to 24, an isotopicallylabeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula,, , , , r,

[0093] wherein “ ” is a point of covalent attachment to ring A.

[0094] 26. The compound of any one of clauses 1 to 13, 15 to 17, or 19 to 24, an isotopicallylabeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula, ,,,,,,,,,,,,,,,, , , ,,, , , ,,, , , , ,,, , , , ,,, , , ,,, , , ,,,, , ,,, , , , ,,,,,

[0095] wherein “ ” is a point of covalent attachment to ring A.

[0096] 27. The compound of any one of clauses 1 to 13, 15 to 17, or 19 to 24, an isotopicallylabeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula,, , , , ,,, , , , , ,,, , , , , ,,, , , ,

[0097] wherein “ ” is a point of covalent attachment to ring A.

[0098] 28. The compound of any one of clauses 1 to 13, 15 to 17, or 19 to 24, an isotopicallylabeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula,, , , , ,,, ,

[0099] wherein “ ” is a point of covalent attachment to ring A.

[0100] 29. The compound of any one of clauses 1 to 13, 15 to 17, or 19 to 24, an isotopicallylabeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula ,

[0101] wherein “ ” is a point of covalent attachment to ring A.

[0102] 30. The compound of any one of clauses 1 to 13, 15 to 17, or 19 to 24, an isotopicallylabeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula,,,, ,,, , , ,,, , , ,,, , ,

[0103] wherein “ ” is a point of covalent attachment to ring A.

[0104] 31. The compound of any one of clauses 1 to 13, 15 to 17, or 19 to 24, an isotopicallylabeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formular,

[0105] wherein “ ” is a point of covalent attachment to ring A.

[0106] 32. The compound of any one of clauses 1 to 13, 15 to 17, or 19 to 24, an isotopicallylabeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula , , ,,, , , ,

[0107] wherein “” is a point of covalent attachment to ring A.

[0108] 33. The compound of any one of clauses 1 to 13, 15 to 17, or 19 to 24, an isotopicallylabeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula ,,, ,,, ,,,,, , , ,,, , , ,,, , ,

[0109] wherein “ ” is a point of covalent attachment to ring A.

[0110] 34. The compound of any one of clauses 1 to 13, 15 to 17, or 19 to 24, an isotopicallylabeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula,, , , ,

[0111] wherein “ ” is a point of covalent attachment to ring A.

[0112] 35. The compound of any one of clauses 1 to 13 or 15 to 17, an isotopically labeledform thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the, r

[0113] wherein “ ” is a point of covalent attachment to ring A.

[0114] 36. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein X is -NR7-.

[0115] 37. The compound of any one of clauses 1 to 35, an isotopically labeled form thereof,or a pharmaceutically acceptable salt thereof, wherein X is -O-.

[0116] 38. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein R6is 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, or -C1-C6alkylene-(5- to 10-membered heteroaryl), wherein each hydrogen atom in 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and -C1-C6alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe,-C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0117] 39. The compound of any one of the preceding clauses, or a pharmaceuticallyacceptable salt thereof, wherein R6is -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in -C1-C6alkylene-(4- to 10-membered heterocycloalkyl) is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0118] 40. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formula , ,, r,

[0119] wherein “” is a point of covalent attachment to X.

[0120] 41. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formula , , , , , , , ,,,,

[0121] wherein “ ” is a point of covalent attachment to X.

[0122] 42. The compound of any one of clauses 1 to 32, an isotopically labeled form thereof,or a pharmaceutically acceptable salt thereof, wherein R6is of the formula

[0123] -CH3,

[0124] wherein “ ” is a point of covalent attachment to X.

[0125] 43. The compound of any one of clauses 1 to 38, an isotopically labeled form thereof,or a pharmaceutically acceptable salt thereof, wherein R6is 4- to 10-membered heterocycloalkyl, wherein each hydrogen atom in 4- to 10-membered heterocycloalkyl, is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0126] 44. The compound of any one of clauses 1 to 38 or 43, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formula,,,,

[0127] wherein “ ” is a point of covalent attachment to X.

[0128] 45. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein two R3, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6cycloalkyl.

[0129] 46. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein two R3, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a 4- to 6-membered heterocycloalkyl.

[0130] 47. The compound of any one of clauses 3 to 6 or 9 to 46, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein Y1, when present, is O.

[0131] 48. The compound of any one of clauses 3 to 6 or 9 to 47, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein Y2, when present, is N.

[0132] 49. The compound of any one of clauses 3 to 6 or 9 to 46, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein Y1, when present, is N.

[0133]

[0134] 50. The compound of any one of clauses 3 to 6, 9 to 47, or 49, an isotopically labeledform thereof, or a pharmaceutically acceptable salt thereof, wherein Y2, when present, is O.

[0135] 51. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein n1 is 0 or 2.

[0136] 52. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein n2 is 0.

[0137] 53. The compound of any one of the preceding clauses, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, wherein m3 is 0.

[0138] 54. The compound of clause 1, selected from the group consisting of:

[0139] 2-amino-3'-{8-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-7,8-dihydro- 6H-pyrimido[5,4-b][1,4]oxazin-4-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0140] 2-amino-3'-{9-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethoxy]-9H-purin-6-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0141] 2-amino-3'-{9-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethoxy]-9H-purin-6-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile;

[0142] 2-amino-3'-{8-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethoxy]-7,8-dihydro-6H- pyrimido[5,4-b][1,4]oxazin-4-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0143] 2-amino-3'-[2-({1-[(dimethylamino)methyl]-2,2-difluorocyclopropyl}methoxy)-8- methyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0144] 2-amino-3'-{9-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-9H-purin-6- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3- carbonitrile;

[0145] 2-amino-3'-{9-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-9H-purin-6- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0146] 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethoxy]pyrimidin-2-yl}-6,7-dihydro-5H- spiro[[1]benzothiophene-4,7'-[5]oxa[4]azatricyclo[6.1.1.02,6]deca[2(6),3]diene]-3- carbonitrile;

[0147] 2-amino-3'-{6-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-2,6,7,8-tetrahydro-9-oxa- 1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0148] 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-methyl-1H-pyrazole-3-carboxamide;

[0149] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0150] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-b]pyridin-6-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0151] 2-amino-3'-{6,7-dimethyl-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-2,6,7,8-tetrahydro-9- oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0152] 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0153] 2-amino-3'-{6-(2-hydroxyethyl)-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-2,6,7,8- tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0154] 2-amino-3'-{1-methyl-7-[1-(1-methylpyrrolidin-2-yl)ethoxy]-1H-imidazo[4,5- b]pyridin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]- 3-carbonitrile;

[0155] 2-amino-10'-[1-(1-methylpyrrolidin-2-yl)ethoxy]-5',5'a,6,6',7,7'-hexahydro-4'H,5H- spiro[[1]benzothiophene-4,3'-[2]oxa[1,9,11]triazadibenzo[cd,h]azulene]-3-carbonitrile;

[0156] 6'-amino-3-{2-[1-(1-methylpyrrolidin-2-yl)ethoxy]pyrimidin-4-yl}-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,4'-thieno[2,3-b]pyran]-5'-carbonitrile;

[0157] 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethoxy]-6,6a,7,8,9,10- hexahydropyrido[1,2-d]pyrimido[5,4-b][1,4]oxazin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0158] 2-amino-3'-{7-(difluoromethyl)-8-ethyl-4-[1-(1-methylpyrrolidin-2-yl)ethoxy]-7,8- dihydro-6H-pyrimido[5,4-b][1,4]oxazin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0159] 2-amino-3'-{8-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,8-dihydro-6H-pyrimido[5,4- b][1,4]oxazin-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0160] 2-amino-3'-{4-(2,2-difluoroethyl)-10-[1-(1-methylpyrrolidin-2-yl)ethyl]-5,6,9,10- tetrahydro-4H,8H-pyrazino[3,2,1-de]pteridin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0161] 2-amino-3'-{4-(4,7-diazaspiro[2.5]octan-7-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0162] 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-(oxolan-3-yl)-1H-pyrazole-3-carboxamide;

[0163] 2'-amino-6'-methyl-3-(1-(1-(1-methylpyrrolidin-2-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5,5',6,6'-tetrahydro-4H-spiro[benzo[d]isoxazole-7,4'- cyclopenta[b]thiophene]-3'-carbonitrile;

[0164] 2-amino-3'-{4-(6-methyl-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0165] 2-amino-3'-{4-(6-methyl-7-oxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl)- 1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0166] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-[7-oxo-6-(oxolan-3-yl)-6,7- dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0167] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-[7-oxo-6-(oxolan-3-yl)-4,5,6,7- tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0168] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-[7-oxo-6-(oxolan-3-yl)-4,5,6,7- tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0169] 2-amino-3'-{4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-1-[1-(1-methylpyrrolidin- 2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0170] 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-(3-methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0171] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(1,4-oxazepan-4-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0172] 2-amino-3'-{3-chloro-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0173] 2-amino-3'-{3-methyl-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0174] 2-amino-3'-{3-fluoro-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0175] 2-amino-3'-{1-methyl-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[4,3- d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0176] 2-amino-3'-{3-[1-(1-methylpyrrolidin-2-yl)ethyl]-1-(propan-2-yl)-1H-pyrazolo[4,3- d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0177] 2-amino-3'-{1-(2-hydroxyethyl)-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[4,3-d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0178] 2-amino-3'-{5-chloro-7-[1-(1-methylpyrrolidin-2-yl)ethyl]-7H-pyrrolo[2,3- d]pyrimidin-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0179] 2-amino-3'-{9-[1-(1-methylpyrrolidin-2-yl)ethyl]-9H-purin-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0180] 2-amino-3'-{3-[1-(1-methylpyrrolidin-2-yl)ethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin- 5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0181] 2-amino-3'-{7-(dimethylamino)-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-3H- [1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0182] 2-amino-3'-{7-(methylamino)-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-3H- [1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0183] 2-amino-3'-(4-{[1-(6-aminopyridin-2-yl)ethyl]amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0184] 2-amino-3'-(4-{[1-(5-amino-1H-pyrazol-3-yl)ethyl]amino}-1-[1-(1-methylpyrrolidin- 2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0185] 2-amino-3'-{4-[(2,2-difluoroethyl)(methyl)amino]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0186] 2-amino-3'-{7-(difluoromethyl)-6-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethyl]- 2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0187] 2-amino-3'-{4-(3-hydroxy-3-methylazepan-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0188] 2-amino-3'-{4-(4-hydroxy-4-methylazepan-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0189] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(3-methyl-4,6,7,8- tetrahydropyrazolo[4,3-c]azepin-5(1H)-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0190] 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[(1-methylpyrrolidin-2- yl)methyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0191] 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)amino]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0192] 2-amino-3'-{2-[1-(1-methylpyrrolidin-2-yl)ethoxy]pyrimidin-4-yl}-6,6',7,7'- tetrahydro-5H,5'H-spiro[[1]benzothiophene-4,8'-imidazo[1,5-a]pyridine]-3-carbonitrile;

[0193] 2-amino-3'-{1-[2-(dimethylamino)cyclobutyl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0194] 2-amino-3'-[1-(1,2-dimethylpiperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0195] 2-amino-3'-(4-{[2-(methanesulfonyl)ethyl](methyl)amino}-1-[1-(1-methylpyrrolidin- 2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0196] 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0197] 2-amino-3'-{4-(3-hydroxy-3-methylpyrrolidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0198] 2-amino-3'-{4-(3,3-difluoropiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0199] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(2-oxa-6-azaspiro[3.5]nonan-6- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0200] 2-amino-3'-{4-(3-hydroxyazetidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0201] 2-amino-3'-{4-(3-hydroxy-3-methylazetidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0202] 2-amino-3'-{4-(6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0203] 2-amino-3'-{4-(methylamino)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0204] 2-amino-3'-{4-(dimethylamino)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0205] 2-amino-3'-{7-hydroxy-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-3H-[1,2,3]triazolo[4,5- d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0206] 1-{2-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-8-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,8-dihydro-6H-pyrimido[5,4- b][1,4]oxazin-4-yl}-N-methyl-1H-pyrazole-3-carboxamide;

[0207] 1-{6-(2-amino-3-cyano-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-4-yl}-N-methyl-1H-pyrazole-3-carboxamide;

[0208] 2-amino-3'-{4-(3-hydroxy-2,2-dimethylazetidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0209] 2-amino-3'-{7-(3-hydroxy-3-methylpiperidin-1-yl)-3-[1-(1-methylpyrrolidin-2- yl)ethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0210] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(1-oxa-6-azaspiro[3.5]nonan-6- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0211] 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0212] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0213] 2-amino-3'-{4-[(2-hydroxypropyl)amino]-3-(1-methyl-1H-pyrazol-3-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0214] 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)amino]-3-(1-methyl-1H-pyrazol-3-yl)-1- [1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0215] 2-amino-3'-{9-hydroxy-9-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethoxy]- 6,6a,7,8,9,10-hexahydropyrido[1,2-d]pyrimido[5,4-b][1,4]oxazin-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0216] (4S)-2-amino-3'-[1-{1-[(2S)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-(3-hydroxy-3- methylpiperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0217] 2-amino-3'-[1-{1-[(2R)-3-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-(3-hydroxy-3- methylpiperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0218] 2-amino-3'-{4-[(2,2-difluorocyclopropyl)amino]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0219] 2-amino-3'-{4-(cyclopropylamino)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0220] 2-amino-3'-(4-{[(1-hydroxycyclobutyl)methyl](methyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0221] 2-amino-3'-{4-[(2-hydroxyethyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0222] 2-amino-3'-{4-[(2-hydroxyethyl)(methyl)amino]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0223] 2-amino-3'-(4-{[(1-hydroxycyclopropyl)methyl]amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0224] 2-amino-3'-{4-(2-hydroxy-2-methylpropoxy)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0225] 2-amino-3'-{4-[(2-hydroxycyclopropyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0226] 2-amino-3'-{1-[1-(dimethylamino)propan-2-yl]-4-(3-hydroxy-3-methylpiperidin-1- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0227] 2-amino-3'-{4-(3-cyano-3-hydroxypiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0228] 2-amino-3'-{4-(3,4-dihydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0229] 2-amino-3'-{4-(3-cyanopiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0230] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(5-oxo-1,4-diazepan-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0231] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(3-oxo-1,4-diazepan-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0232] 2-amino-3'-{4-(4-cyanoazepan-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0233] 2-amino-3'-{4-[5-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0234] 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-6-[1-(1-methylpyrrolidin-2- yl)ethoxy]pyrimidin-2-yl}-4',5',6,6',7,7'-hexahydro-5H-spiro[[1]benzothiophene-4,8'- cyclohepta[d][1,2]oxazole]-3-carbonitrile;

[0235] 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethoxy]pyrimidin-2-yl}-4',5',6,6',7,7'- hexahydro-5H-spiro[[1]benzothiophene-4,8'-cyclohepta[d][1,2]oxazole]-3-carbonitrile;

[0236] 2-amino-3'-{4-[(2-hydroxycyclopropyl)amino]-3-methoxy-1-[1-(1-methylpyrrolidin- 2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0237] 2-amino-3'-{3-cyano-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0238] 2-amino-3'-{3-cyano-4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin- 2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0239] 2-amino-3'-{3-cyano-4-[(2-hydroxy-2-methylpropyl)amino]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0240] 2-amino-3'-{4-[ethyl(2-hydroxy-2-methylpropyl)amino]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0241] 2-amino-3'-{4-[(2,2-difluoroethyl)(2-hydroxy-2-methylpropyl)amino]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0242] 2-amino-3'-(4-{[(1-hydroxycyclopropyl)methyl](methyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0243] 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-(1-methylazetidin-3- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0244] 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-(1-methylpyrrolidin-3- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0245] 2-amino-3'-{1-(4-fluoro-1-methylpyrrolidin-3-yl)-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0246] 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0247] 2-amino-3'-{1-[1-(3-fluoro-1-methylpyrrolidin-2-yl)ethyl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0248] 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-[1-(3-methoxy-1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0249] 2-amino-3'-{1-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0250] 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-[1-(1- methylpyrrolidin-2-yl)ethyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0251] 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-[1-(1- methylpyrrolidin-2-yl)ethyl]-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0252] 2-amino-3'-{4-[(1-hydroxycyclopropyl)methoxy]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0253] 2-amino-3'-{7-[(2-hydroxy-2-methylpropyl)(methyl)amino]-3-[1-(1- methylpyrrolidin-2-yl)ethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0254] 2-amino-3'-{1-[4-(dimethylamino)oxolan-3-yl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0255] 2-amino-3'-(4-{[(1-cyanocyclopropyl)methyl]amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0256] 2-amino-3'-[8-(1,2-dimethylpiperidin-3-yl)-7,8-dihydro-6H-pyrimido[5,4- b][1,4]oxazin-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0257] 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}piperidine-3-carboxamide;

[0258] 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-tert-butyl-3-hydroxypiperidine-3-carboxamide;

[0259] 2-amino-3'-[3-(1-methyl-1H-pyrazol-3-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4- (methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0260] 2-amino-3'-{4-hydroxy-3-(1-methyl-1H-pyrazol-3-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0261] 5-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N,N-dimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxamide;

[0262] 2-amino-3'-{4-[3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0263] 2-amino-3'-{4-(2,2-dioxo-2λ6-thia-1,3,7-triazaspiro[4.5]decan-7-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0264] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(4-oxa-7-azaspiro[2.5]octan-7- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0265] 2-amino-3'-{4-(2-cyanomorpholin-4-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0266] 2-amino-3'-(4-{[(3-hydroxyoxetan-3-yl)methyl](methyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0267] 2-amino-3'-{4-(2,5-dioxa-8-azaspiro[3.5]nonan-8-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0268] 2-amino-3'-{4-[3-(methanesulfonyl)pyrrolidin-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0269] 2-amino-3'-{4-[(2,2-difluoroethyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0270] 2-amino-3'-{4-(3-hydroxypiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0271] 2-amino-3'-{4-[3-hydroxy-3-(trifluoromethyl)piperidin-1-yl]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0272] 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-3-hydroxypiperidine-3-carboxamide;

[0273] 2-amino-3'-{1-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-4-(methylsulfanyl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0274] 2-amino-3'-{4-(3-cyano-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0275] 2-amino-3'-{4-[(2-cyanopropyl)(methyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0276] 2-amino-3'-[1-{1-[1-(2-hydroxyethyl)pyrrolidin-2-yl]ethyl}-4-(3-hydroxy-3- methylpiperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0277] 2-amino-3'-{4-[3-(methanesulfonyl)piperidin-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0278] 2-amino-3'-{4-(3-hydroxy-3,5-dimethylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0279] 2-amino-3'-{1-[1-(1-cyclopropylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3- methylpiperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0280] 2-amino-3'-{3-cyano-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(methylsulfanyl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0281] methyl 6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidine- 3-carboxylate;

[0282] 2-amino-3'-{4-[3-(2-hydroxypropan-2-yl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin- 2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0283] 2-amino-3'-{4-(ethylamino)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0284] 2-amino-3'-[3-chloro-1-(1,2-dimethylpiperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6- yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0285] 2-amino-3'-{4-(3-methyl-1H-pyrazol-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0286] 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-methyl-1H-pyrazole-4-carboxamide;

[0287] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(piperidin-1-yl)-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0288] 2-amino-3'-{4-[3-(hydroxymethyl)-4-methyl-1H-pyrazol-1-yl]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0289] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(methylsulfanyl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0290] 2-amino-3'-{4-[4-fluoro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0291] 2-amino-3'-{4-(4-chloro-3-methyl-1H-pyrazol-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0292] 3'-{4-(3-acetyl-1H-pyrazol-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-2-amino-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0293] 2-amino-3'-{4-(3-cyano-4-hydroxypiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0294] 2-amino-3'-{4-[4-chloro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0295] 2-amino-3'-{4-[3-(difluoromethyl)-3-hydroxypiperidin-1-yl]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0296] 2-amino-3'-{4-[3-(1-hydroxyethyl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0297] 2-amino-3'-{4-[3-(hydroxymethyl)azetidin-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0298] 2-amino-3'-{4-[3-(hydroxymethyl)pyrrolidin-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0299] 2-amino-3'-{4-[4-(hydroxymethyl)-2H-1,2,3-triazol-2-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0300] 2-amino-3'-{4-[4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0301] 2-amino-3'-{4-(3,5-dihydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0302] 2-amino-3'-{4-(5-hydroxy-2,5-dimethylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0303] 2-amino-3'-{4-(3-cyano-1H-pyrazol-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0304] 2-amino-3'-{4-[8-(methoxyimino)-3-azabicyclo[3.2.1]octan-3-yl]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0305] 2-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-methyl-2H-1,2,3-triazole-4-carboxamide;

[0306] 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-methyl-1H-1,2,3-triazole-4-carboxamide;

[0307] 2-amino-3'-{4-(4-cyano-1H-pyrazol-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0308] 2-amino-3'-{4-[4-(methoxyimino)piperidin-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0309] 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(pyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0310] 2-amino-3'-{3-(1-methyl-1H-pyrazol-3-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0311] 2-amino-3'-{1-[1-(1-ethylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3-methylpiperidin-1- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0312] 6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidine- 3-carboxamide;

[0313] 2-amino-3'-{4-(4-aminopiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0314] 2-amino-3'-{4-(8-amino-3-azabicyclo[3.2.1]octan-3-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0315] 2-amino-3'-{4-(3-hydroxy-5-methoxy-3-methylpiperidin-1-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0316] 2-amino-3'-{4-(6-hydroxy-5,6-dihydrocyclopenta[c]pyrazol-2(4H)-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0317] 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0318] 2-amino-3'-{4-[3-(hydroxymethyl)-1H-pyrrol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0319] 2-amino-3'-{3-cyano-4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0320] 2-amino-3'-{3-[1-(2-hydroxyethyl)-1H-pyrazol-3-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0321] 2-amino-3'-{4-[6-(hydroxymethyl)pyridin-2-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0322] 2-amino-3'-{4-[5-fluoro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0323] 2-amino-3'-{6-(3-hydroxy-3-methylpiperidin-1-yl)-9-[1-(1-methylpyrrolidin-2- yl)ethyl]-9H-purin-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0324] 2-amino-3'-{4-(7-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0325] 2-amino-3'-[4-(3-hydroxy-3-methylpiperidin-1-yl)-1-{1-[1-(2H3)methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0326] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0327] 2-amino-3'-{1-[1-(1-ethylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3-methylpiperidin-1- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'- pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0328] 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-1H-pyrazole-3-sulfonamide;

[0329] 2-amino-3'-{1-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3- methylpiperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0330] 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-7-[1-(1-methylpyrrolidin-2- yl)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0331] 2-amino-3'-{4-[(2-cyano-2-methylpropyl)(methyl)amino]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0332] 2-amino-3'-{4-(5-fluoro-3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0333] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-6,7- dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0334] 2-amino-3'-{4-(3,5-dihydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0335] 2-amino-3'-{4-(3-cyano-4-hydroxypiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0336] 2-amino-3'-{1-[1-(1-ethylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3-methylpiperidin-1- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene- 4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0337] 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(pyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0338] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0339] 2-amino-3'-{3-chloro-4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0340] 2-amino-3'-{3-cyano-4-(2-hydroxy-2-methylpropoxy)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0341] 2-amino-3'-{3-cyano-4-[3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0342] 2-amino-3'-{3-cyano-1-[1-(1-ethylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3- methylpiperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0343] 2-amino-3'-{3-cyano-4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(pyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0344] 2-amino-3'-{4-[2-(hydroxymethyl)-1H-pyrrol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0345] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a-hexaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0346] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-4',5',6,7- tetrahydro-5H-spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0347] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(pyrrolidin-2-yl)ethyl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0348] 2-amino-3'-{4-[1-(1-ethylpyrrolidin-2-yl)ethyl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0349] 2-amino-3'-{4-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0350] 2-amino-3'-{4-[1-(3-fluoro-1-methylpyrrolidin-2-yl)ethyl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0351] 2-amino-3'-{10-hydroxy-4-[1-(3-methoxy-1-methylpyrrolidin-2-yl)ethyl]-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0352] 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,7a,8,9,10,11-hexahydro-4H-6- oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0353] 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7a,8,9,10,11,12-hexahydro-4H,7H- 6-oxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0354] 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,7a,8,9,11,12-hexahydro-4H-6,10- dioxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0355] 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7a,8,11,12-tetrahydro-4H,7H,10H- 6,9-dioxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0356] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 4,7a,8,9,10,11-hexahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0357] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-thia-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0358] 2-amino-3'-{1-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0359] 2-amino-3'-{7-(3-hydroxy-3-methylpiperidin-1-yl)-3-[1-(1-methylpyrrolidin-2- yl)ethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0360] 2-amino-3'-{3-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-7-(3-hydroxy-3- methylpiperidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0361] 2-amino-3'-{3-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-7-(3-hydroxy-3- methylpiperidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0362] 2-amino-3'-{7-(3-hydroxy-3-methylpiperidin-1-yl)-3-[1-(1-methylpyrrolidin-2- yl)ethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0363] 2-amino-3'-{3-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-7-(3-hydroxy-3- methylpiperidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0364] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylazetidin-2-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0365] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1,4,4-trimethylazetidin-2-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0366] 2-amino-3'-{4-[1-(dimethylamino)propan-2-yl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0367] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-6,6-dioxo- 4,6,7,7a,8,9,10,11-octahydro-6λ6-thia-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0368] 2-amino-3'-[10-hydroxy-10-methyl-4-(1-methyloctahydro-1H-indol-7-yl)- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0369] (4S)-2-amino-3'-[10-hydroxy-10-methyl-4-(1-methyloctahydropyrano[4,3-b]pyrrol-7- yl)-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0370] 3'-{4-hydroxy-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl}-2-{[(1H-pyrrol-2-yl)methyl]amino}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0371] 2-amino-3'-{9-hydroxy-9-methyl-6-methylidene-4-[1-(1-methylpyrrolidin-2- yl)ethyl]-6,6a,7,8,9,10-hexahydro-4H-1,3,4,5,10a-pentaazaacephenanthrylen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0372] 2-amino-3'-{3-cyano-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(piperidin-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0373] 2-amino-3'-[4-(3-hydroxy-3-methylpiperidin-1-yl)-1-(1-methyloctahydro-1H-indol-7- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0374] 2-amino-3'-{1-(2-hydroxy-2-methylpropyl)-4-[1-(1-methylpyrrolidin-2-yl)ethoxy]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0375] 2-amino-3'-{4-[1-(hexahydro-1H-pyrrolizin-3-yl)ethyl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0376] 2-amino-3'-{10-hydroxy-10-methyl-4-[3-(pyrrolidin-1-yl)butan-2-yl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0377] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(pyrrolidin-1-yl)propan-2-yl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0378] 2-amino-3'-{4-[3-(azetidin-1-yl)butan-2-yl]-10-hydroxy-10-methyl-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0379] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7-oxo- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a-hexaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0380] 2-amino-3'-{10-hydroxy-6,10-dimethyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7-oxo- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a-hexaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0381] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(pyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0382] 2-amino-3'-{3-[1-(3-hydroxycyclobutyl)-1H-pyrazol-3-yl]-1-[1-(1-methylpyrrolidin- 2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0383] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-methyl-1H- pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0384] 2-amino-3'-[4-(7-amino-6-methyl-1,3,4,6-tetrahydro-5H-pyrido[3,4-f][1,4]oxazocin- 5-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0385] 2-amino-3'-{3-[1-(2-hydroxypropyl)-1H-pyrazol-3-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0386] 2-amino-3'-{10-hydroxy-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0387] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl]amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0388] 2-amino-3'-{4-[1-(2-aminopyridin-3-yl)ethoxy]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0389] 2-amino-3'-{3-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-3-yl]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0390] 2-amino-3'-{4-[2-(dimethylamino)cyclopentyl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0391] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(4-methyl-2,4,6,7-tetrahydro-5H- pyrazolo[4,3-f][1,4]oxazepin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0392] 2-amino-3'-{4-[2-(azetidin-1-yl)cyclopentyl]-10-hydroxy-10-methyl-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0393] 2-amino-3'-{4-[2-(2-aminopyridin-3-yl)pyrrolidin-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0394] 2-amino-3'-{6-[(2-aminopyridin-3-yl)methyl]-2-[1-(1-methylpyrrolidin-2-yl)ethyl]- 2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0395] 2-amino-3'-{7-(2-aminopyridin-3-yl)-6-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethyl]- 2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0396] 2-amino-3'-(4-{[1-(3-aminopyrazin-2-yl)ethyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0397] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0398] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0399] 2-amino-3'-{6-[1-(5-methyl-1H-pyrazol-4-yl)ethyl]-2-[1-(1-methylpyrrolidin-2- yl)ethyl]-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0400] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(4-methyl-2,6,7,9- tetrahydropyrazolo[4,3-f][1,4]oxazocin-5(4H)-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0401] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(4-methyl-2,4,7,8- tetrahydropyrazolo[3,4-b][1,5]oxazocin-5(6H)-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0402] 2-amino-3'-{6-[1-(2-aminopyridin-3-yl)ethyl]-2-[1-(1-methylpyrrolidin-2-yl)ethyl]- 2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0403] 2-amino-3'-{4-(6-amino-5-methyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin-4(5H)-yl)- 1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0404] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(4-fluoro-1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0405] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](2-cyanoethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0406] 2-amino-3'-{4-(7-amino-6-methyl-1,3,4,6-tetrahydro-5H-pyrido[3,4-f][1,4]oxazocin- 5-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0407] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](2,2-difluoroethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0408] 2-[4-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-7-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,8-dihydro-9-oxa- 1,2,3,5,6-pentaazabenzo[cd]azulen-6(2H)-yl]-1,4-anhydro-2,3,5-trideoxypentitol;

[0409] 2-[4-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,8-dihydro-9-oxa-1,2,3,5,6- pentaazabenzo[cd]azulen-6(2H)-yl]-1,4-anhydro-2,3,5-trideoxypentitol;

[0410] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(tetrahydro-1H-pyrrolizin-7a(5H)-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0411] 2-amino-3'-{9-hydroxy-6,9-dimethyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 6,6a,7,8,9,10-hexahydro-4H-1,3,4,5,10a-pentaazaacephenanthrylen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0412] 2-amino-3'-{2-(2-hydroxy-2-methylpropyl)-6-[1-(1-methylpyrrolidin-2-yl)ethyl]- 2,6,7,8-tetrahydro-1,2,3,5,6-pentaazaacenaphthylen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0413] 2-[2-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-9-[1-(1-methylpyrrolidin-2-yl)ethyl]-5-oxo-8,9-dihydro-7H- imidazo[4,5,1-de]pteridin-4(5H)-yl]-1,4-anhydro-2,3,5-trideoxypentitol;

[0414] 2-amino-3'-{9-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(3-oxabicyclo[3.1.0]hexan-1-yl)- 5-oxo-4,5,8,9-tetrahydro-7H-imidazo[4,5,1-de]pteridin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0415] 2-amino-3'-{4-(2-hydroxy-2-methylpropyl)-9-[1-(1-methylpyrrolidin-2-yl)ethyl]-5- oxo-4,5,8,9-tetrahydro-7H-imidazo[4,5,1-de]pteridin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0416] 2-amino-3'-{9-[1-(1-methylpyrrolidin-2-yl)ethyl]-5-oxo-4-(oxolan-3-yl)-4,5,8,9- tetrahydro-7H-imidazo[4,5,1-de]pteridin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0417] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-4',5',6,7- tetrahydro-5H-spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0418] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(tetrahydro-1H-pyrrolizin-7a(5H)-yl)ethyl]- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0419] 2-amino-3'-{4-[1-(1-ethylpyrrolidin-2-yl)ethyl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0420] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(3-oxo-2,8-diazaspiro[4.5]decan- 8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0421] 2-amino-3'-{4-(2-ethyl-5-hydroxy-5-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin- 2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0422] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl](6,6,7,7-2H4)-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0423] 2-amino-3'-{9-hydroxy-6,9-dimethyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,8,9,10- tetrahydro-4H-1,3,4,5,10a-pentaazaacephenanthrylen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0424] 2-amino-3'-(4-{[3-(1-hydroxyethyl)pyridin-2-yl]amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0425] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylazetidin-2-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0426] 2-amino-3'-[10-hydroxy-10-(2H3)methyl-4-{1-[1-(2H3)methylpyrrolidin-2-yl]ethyl}- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0427] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-6-oxo- 4,6,7,7a,8,9,10,11-octahydro-6λ4-thia-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0428] 2-amino-3'-{4-(4-cyano-2-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0429] 2-amino-3'-{10-hydroxy-7,10-dimethyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0430] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](methyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0431] 2-amino-3'-(4-{ethyl[1-(6-hydroxypyridin-3-yl)ethyl]amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0432] 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(6-oxa-1-azaspiro[3.5]nonan-1- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0433] 2-amino-3'-{8-hydroxy-8-methyl-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1,3,5,5a,6,7,8,9-octahydro-4-oxa-1,2,9a,10,12-pentaazabenzo[4,5]cycloocta[1,2,3-cd]inden- 11-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0434] 3'-{4-[(1-acetylpyrrolidin-3-yl)(ethyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-2-amino-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0435] 5-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N,N,3-trimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxamide;

[0436] 2-amino-3'-{4-[2-(hydroxymethyl)-2-methylazetidin-1-yl]-1-[1-(1-methylpyrrolidin- 2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0437] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-6,7-dihydro- 4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0438] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl](7,7-2H2)- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0439] 2-amino-3'-[(7aS)-10-hydroxy-10-methyl-4-{1-[1-(2H3)methylpyrrolidin-2-yl]ethyl}- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0440] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile;

[0441] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl]amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0442] 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](methyl)amino}methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile;

[0443] 2-amino-3'-{6-ethyl-10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7- oxo-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a-hexaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0444] 2-amino-3'-(4-{[(3,5-dimethyl-1H-pyrazol-4-yl)methyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0445] 2-amino-3'-{4-[1-(1,5-dimethylpyrrolidin-2-yl)ethyl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0446] 2-amino-3'-(4-{[(2-aminopyridin-3-yl)methyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0447] 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1,5,5-trimethylpyrrolidin-2-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0448] 2-amino-3'-(4-{[1-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; and

[0449] 2-amino-3'-(4-{[1-(2-amino-6-methylpyridin-3-yl)ethyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0450] 55. The compound of clause 1, selected from the group consisting of:

[0451] (4S)-2-amino-3'-{8-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-7,8- dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0452] (4S)-2-amino-3'-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H- purin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0453] (4S)-2-amino-3'-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H- purin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3- carbonitrile;

[0454] (4S)-2-amino-3'-(8-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-7,8- dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0455] (4S)-2-amino-3'-[2-({(1S)-1-[(dimethylamino)methyl]-2,2- difluorocyclopropyl}methoxy)-8-methyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0456] (4S)-2-amino-3'-[2-({(1R)-1-[(dimethylamino)methyl]-2,2- difluorocyclopropyl}methoxy)-8-methyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0457] (4S)-2-amino-3'-{9-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-9H- purin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3- carbonitrile;

[0458] (4S)-2-amino-3'-{9-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-9H- purin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0459] (4R)-2-amino-3'-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 6,7-dihydro-5H-spiro[[1]benzothiophene-4,7'- [5]oxa[4]azatricyclo[6.1.1.02,6]deca[2(6),3]diene]-3-carbonitrile;

[0460] (4S)-2-amino-3'-(6-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-2,6,7,8- tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0461] 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-N-methyl-1H-pyrazole-3-carboxamide;

[0462] 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1R)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-N-methyl-1H-pyrazole-3-carboxamide;

[0463] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0464] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- b]pyridin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]- 3-carbonitrile;

[0465] (4S)-2-amino-3'-[(7R)-6,7-dimethyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0466] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0467] (4S)-2-amino-3'-[6-(2-hydroxyethyl)-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl]-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0468] (4S)-2-amino-3'-(1-methyl-7-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-1H- imidazo[4,5-b]pyridin-5-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0469] (3'R,5'aS)-2-amino-10'-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-5',5'a,6,6',7,7'- hexahydro-4'H,5H-spiro[[1]benzothiophene-4,3'-[2]oxa[1,9,11]triazadibenzo[cd,h]azulene]- 3-carbonitrile;

[0470] (4'S)-6'-amino-3-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- 2',3',5,6-tetrahydro-4H-spiro[[1,2]benzoxazole-7,4'-thieno[2,3-b]pyran]-5'-carbonitrile;

[0471] (4S)-2-amino-3'-[(6aR)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}- 6,6a,7,8,9,10-hexahydropyrido[1,2-d]pyrimido[5,4-b][1,4]oxazin-2-yl]-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0472] (4S)-2-amino-3'-[(7S)-7-(difluoromethyl)-8-ethyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0473] (4S)-2-amino-3'-(8-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,8-dihydro-6H- pyrimido[5,4-b][1,4]oxazin-2-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0474] (4S)-2-amino-3'-[4-(2,2-difluoroethyl)-10-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-5,6,9,10-tetrahydro-4H,8H-pyrazino[3,2,1-de]pteridin-2-yl]-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0475] (4S)-2-amino-3'-[4-(4,7-diazaspiro[2.5]octan-7-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0476] 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-N-[(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide;

[0477] 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide; and

[0478] (6'S,7S)-2'-amino-6'-methyl-3-(1-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethyl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl)-5,5',6,6'-tetrahydro-4H-spiro[benzo[d]isoxazole-7,4'- cyclopenta[b]thiophene]-3'-carbonitrile;

[0479] (4S)-2-amino-3'-[4-(6-methyl-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl)-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0480] (4S)-2-amino-3'-[4-(6-methyl-7-oxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2- yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0481] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3S)- oxolan-3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0482] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3R)- oxolan-3-yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0483] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3S)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0484] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3R)- oxolan-3-yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0485] (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0486] (4S)-2-amino-3'-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0487] 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-N-(3-methyloxetan-3-yl)-1H-pyrazole-3-carboxamide;

[0488] (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(1,4-oxazepan-4- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0489] (4S)-2-amino-3'-(3-chloro-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0490] (4S)-2-amino-3'-(3-methyl-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0491] (4S)-2-amino-3'-(3-fluoro-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0492] (4S)-2-amino-3'-(1-methyl-3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[4,3-d]pyrimidin-5-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0493] (4S)-2-amino-3'-[3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1-(propan-2-yl)-1H- pyrazolo[4,3-d]pyrimidin-5-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0494] (4S)-2-amino-3'-[1-(2-hydroxyethyl)-3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 1H-pyrazolo[4,3-d]pyrimidin-5-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0495] (4S)-2-amino-3'-(5-chloro-7-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7H- pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0496] (4S)-2-amino-3'-(9-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-9H-purin-2-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0497] (4S)-2-amino-3'-(3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-3H- [1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0498] (4S)-2-amino-3'-[7-(dimethylamino)-3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0499] (4S)-2-amino-3'-[7-(methylamino)-3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0500] (4S)-2-amino-3'-(4-{[(1R)-1-(6-aminopyridin-2-yl)ethyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0501] (4S)-2-amino-3'-(4-{[(1R)-1-(5-amino-1H-pyrazol-3-yl)ethyl]amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0502] (4S)-2-amino-3'-(4-[(2,2-difluoroethyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0503] (4S)-2-amino-3'-[(7S)-7-(difluoromethyl)-6-methyl-2-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4- yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0504] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylazepan-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0505] (4S)-2-amino-3'-(4-[(3S)-3-hydroxy-3-methylazepan-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0506] (4S)-2-amino-3'-(4-[(4R)-4-hydroxy-4-methylazepan-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0507] (4S)-2-amino-3'-(4-[(4S)-4-hydroxy-4-methylazepan-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0508] (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(3-methyl-4,6,7,8- tetrahydropyrazolo[4,3-c]azepin-5(1H)-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0509] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{[(2S)-1- methylpyrrolidin-2-yl]methyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0510] (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0511] (4R)-2-amino-3'-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-6,6',7,7'-tetrahydro-5H,5'H-spiro[[1]benzothiophene-4,8'-imidazo[1,5-a]pyridine]-3- carbonitrile;

[0512] (4S)-2-amino-3'-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)- 6,6',7,7'-tetrahydro-5H,5'H-spiro[[1]benzothiophene-4,8'-imidazo[1,5-a]pyridine]-3- carbonitrile;

[0513] (4S)-2-amino-3'-{1-[(1S,2S)-2-(dimethylamino)cyclobutyl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0514] (4S)-2-amino-3'-{1-[(2R,3R)-1,2-dimethylpiperidin-3-yl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0515] (4S)-2-amino-3'-(4-{[2-(methanesulfonyl)ethyl](methyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0516] (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0517] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0518] (4S)-2-amino-3'-[4-(3,3-difluoropiperidin-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0519] (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(2-oxa-6- azaspiro[3.5]nonan-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0520] (4S)-2-amino-3'-[4-(3-hydroxyazetidin-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0521] (4S)-2-amino-3'-[4-(3-hydroxy-3-methylazetidin-1-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0522] (4S)-2-amino-3'-[4-(6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0523] (4S)-2-amino-3'-[4-(methylamino)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0524] (4S)-2-amino-3'-[4-(dimethylamino)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0525] (4S)-2-amino-3'-(7-hydroxy-3-{1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-3H- [1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0526] 1-(2-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-8-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,8-dihydro-6H- pyrimido[5,4-b][1,4]oxazin-4-yl)-N-methyl-1H-pyrazole-3-carboxamide;

[0527] 1-(6-[(4S)-2-amino-3-cyano-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-N-methyl-1H-pyrazole-3-carboxamide;

[0528] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-2,2-dimethylazetidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0529] (4S)-2-amino-3'-(7-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-3-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0530] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4S)-1-oxa-6- azaspiro[3.5]nonan-6-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0531] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0532] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0533] (4S)-2-amino-3'-(4-{[(2S)-2-hydroxypropyl]amino}-3-(1-methyl-1H-pyrazol-3-yl)-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0534] (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)amino]-3-(1-methyl-1H-pyrazol-3-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0535] (4S)-2-amino-3'-[(6aR,9R)-9-hydroxy-9-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethoxy}-6,6a,7,8,9,10-hexahydropyrido[1,2-d]pyrimido[5,4-b][1,4]oxazin-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0536] (4S)-2-amino-3'-(1-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(3R)- 3-hydroxy-3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0537] (4S)-2-amino-3'-(1-{1-[(2R,3S)-3-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(3R)-3- hydroxy-3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0538] (4S)-2-amino-3'-(1-{(1S)-1-[(2R,3S)-3-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(3R)- 3-hydroxy-3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0539] (4S)-2-amino-3'-(4-[(2,2-difluorocyclopropyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0540] (4S)-2-amino-3'-[4-(cyclopropylamino)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0541] (4S)-2-amino-3'-(4-{[(1-hydroxycyclobutyl)methyl](methyl)amino}-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0542] (4S)-2-amino-3'-(4-[(2-hydroxyethyl)amino]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0543] (4S)-2-amino-3'-(4-[(2-hydroxyethyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0544] (4S)-2-amino-3'-(4-{[(1-hydroxycyclopropyl)methyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0545] (4S)-2-amino-3'-[4-(2-hydroxy-2-methylpropoxy)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0546] (4S)-2-amino-3'-(4-[(2-hydroxycyclopropyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0547] (4S)-2-amino-3'-(4-{[(1S,2S)-2-hydroxycyclopropyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0548] (4S)-2-amino-3'-(4-{[(1R,2R)-2-hydroxycyclopropyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0549] (4S)-2-amino-3'-{1-[(2S)-1-(dimethylamino)propan-2-yl]-4-[(3R)-3-hydroxy-3- methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0550] (4S)-2-amino-3'-(4-[(3R)-3-cyano-3-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0551] (4S)-2-amino-3'-(4-[(3S,4S)-3,4-dihydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0552] (4S)-2-amino-3'-(4-[(3S,4R)-3,4-dihydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0553] (4S)-2-amino-3'-(4-[(3R,4R)-3,4-dihydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0554] (4S)-2-amino-3'-(4-[(3R)-3-cyanopiperidin-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0555] (4S)-2-amino-3'-(4-[(3S)-3-cyanopiperidin-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0556] (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(5-oxo-1,4- diazepan-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0557] (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(3-oxo-1,4- diazepan-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0558] (4S)-2-amino-3'-(4-[(4S)-4-cyanoazepan-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0559] (4S)-2-amino-3'-(4-[(4R)-4-cyanoazepan-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0560] (4S)-2-amino-3'-(4-[5-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0561] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-4',5',6,6',7,7'-hexahydro-5H- spiro[[1]benzothiophene-4,8'-cyclohepta[d][1,2]oxazole]-3-carbonitrile;

[0562] (4R)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-4',5',6,6',7,7'-hexahydro-5H- spiro[[1]benzothiophene-4,8'-cyclohepta[d][1,2]oxazole]-3-carbonitrile;

[0563] (4S)-2-amino-3'-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 4',5',6,6',7,7'-hexahydro-5H-spiro[[1]benzothiophene-4,8'-cyclohepta[d][1,2]oxazole]-3- carbonitrile;

[0564] (4S)-2-amino-3'-(4-{[(1S,2S)-2-hydroxycyclopropyl]amino}-3-methoxy-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0565] (4S)-2-amino-3'-(4-{[(1R,2R)-2-hydroxycyclopropyl]amino}-3-methoxy-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0566] (4S)-2-amino-3'-(3-cyano-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0567] (4S)-2-amino-3'-(3-cyano-4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0568] (4S)-2-amino-3'-(3-cyano-4-[(2-hydroxy-2-methylpropyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0569] (4S)-2-amino-3'-(4-[ethyl(2-hydroxy-2-methylpropyl)amino]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0570] (4S)-2-amino-3'-(4-[(2,2-difluoroethyl)(2-hydroxy-2-methylpropyl)amino]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0571] (4S)-2-amino-3'-(4-{[(1-hydroxycyclopropyl)methyl](methyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0572] (4S)-2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-(1- methylazetidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0573] (4S)-2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-[(3S)-1- methylpyrrolidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0574] (4S)-2-amino-3'-{1-[(3R,4S)-4-fluoro-1-methylpyrrolidin-3-yl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0575] (4S)-2-amino-3'-{1-[(3R,4R)-4-fluoro-1-methylpyrrolidin-3-yl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0576] (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0577] (4S)-2-amino-3'-(1-{(1S)-1-[(2R,3S)-3-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(2- hydroxy-2-methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0578] (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2R,3S)- 3-methoxy-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0579] (4S)-2-amino-3'-(1-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(2- hydroxy-2-methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0580] (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0581] (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-{1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0582] (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0583] (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-{(1R)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0584] (4S)-2-amino-3'-(4-[(1-hydroxycyclopropyl)methoxy]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0585] (4S)-2-amino-3'-(7-[(2-hydroxy-2-methylpropyl)(methyl)amino]-3-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0586] (4S)-2-amino-3'-(7-[(2-hydroxy-2-methylpropyl)(methyl)amino]-3-{(1R)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0587] (4S)-2-amino-3'-{1-[4-(dimethylamino)oxolan-3-yl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0588] (4S)-2-amino-3'-{1-[(3R,4R)-4-(dimethylamino)oxolan-3-yl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0589] (4S)-2-amino-3'-(4-{[(1-cyanocyclopropyl)methyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0590] (4S)-2-amino-3'-{8-[(2R,3R)-1,2-dimethylpiperidin-3-yl]-7,8-dihydro-6H- pyrimido[5,4-b][1,4]oxazin-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0591] (3S)-1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidine-3-carboxamide;

[0592] 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-tert-butyl-3-hydroxypiperidine-3-carboxamide;

[0593] (4S)-2-amino-3'-[3-(1-methyl-1H-pyrazol-3-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-4-(methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0594] (4S)-2-amino-3'-[4-hydroxy-3-(1-methyl-1H-pyrazol-3-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0595] 5-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-N,N-dimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5- a][1,4]diazepine-2-carboxamide;

[0596] (4S)-2-amino-3'-(4-[3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0597] (4S)-2-amino-3'-(4-[(5R)-2,2-dioxo-2λ6-thia-1,3,7-triazaspiro[4.5]decan-7-yl]-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0598] (4S)-2-amino-3'-(4-[(5S)-2,2-dioxo-2λ6-thia-1,3,7-triazaspiro[4.5]decan-7-yl]-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0599] (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(4-oxa-7- azaspiro[2.5]octan-7-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0600] (4S)-2-amino-3'-(4-[(2S)-2-cyanomorpholin-4-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0601] (4S)-2-amino-3'-(4-{[(3-hydroxyoxetan-3-yl)methyl](methyl)amino}-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0602] (4S)-2-amino-3'-[4-(2,5-dioxa-8-azaspiro[3.5]nonan-8-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0603] (4S)-2-amino-3'-(4-[(3R)-3-(methanesulfonyl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0604] (4S)-2-amino-3'-(4-[(3S)-3-(methanesulfonyl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0605] (4S)-2-amino-3'-(4-[(2,2-difluoroethyl)amino]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0606] (4S)-2-amino-3'-(4-[(3R)-3-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0607] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-(trifluoromethyl)piperidin-1-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0608] (4S)-2-amino-3'-(4-[(3S)-3-hydroxy-3-(trifluoromethyl)piperidin-1-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0609] (3R)-1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-hydroxypiperidine-3-carboxamide;

[0610] (3S)-1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-hydroxypiperidine-3-carboxamide;

[0611] (4S)-2-amino-3'-[1-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4- (methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0612] (4S)-2-amino-3'-(4-[(3S)-3-cyano-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0613] (4S)-2-amino-3'-(4-[(3R)-3-cyano-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0614] (4S)-2-amino-3'-(4-[(2-cyanopropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0615] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-(2-hydroxyethyl)pyrrolidin-2-yl]ethyl}-4-[(3R)-3- hydroxy-3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0616] (4S)-2-amino-3'-(4-[(3S)-3-(methanesulfonyl)piperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0617] (4S)-2-amino-3'-(4-[(3R)-3-(methanesulfonyl)piperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0618] (4S)-2-amino-3'-(4-[(3R,5R)-3-hydroxy-3,5-dimethylpiperidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0619] (4S)-2-amino-3'-(4-[(3S,5R)-3-hydroxy-3,5-dimethylpiperidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0620] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-cyclopropylpyrrolidin-2-yl]ethyl}-4-[(3R)-3- hydroxy-3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0621] (4S)-2-amino-3'-[3-cyano-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4- (methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0622] methyl 6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylate;

[0623] (4S)-2-amino-3'-(4-[3-(2-hydroxypropan-2-yl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0624] (4S)-2-amino-3'-[4-(ethylamino)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0625] (4S)-2-amino-3'-{3-chloro-1-[(2R,3R)-1,2-dimethylpiperidin-3-yl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0626] (4S)-2-amino-3'-[4-(3-methyl-1H-pyrazol-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0627] 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-N-methyl-1H-pyrazole-4-carboxamide;

[0628] (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(piperidin-1-yl)- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0629] (4S)-2-amino-3'-(4-[3-(hydroxymethyl)-4-methyl-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0630] (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(methylsulfanyl)- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0631] (4S)-2-amino-3'-(4-[4-fluoro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0632] (4S)-2-amino-3'-[4-(4-chloro-3-methyl-1H-pyrazol-1-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0633] (4S)-3'-[4-(3-acetyl-1H-pyrazol-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]-2-amino-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0634] (4S)-2-amino-3'-(4-[(3R,4S)-3-cyano-4-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0635] (4S)-2-amino-3'-(4-[(3S,4R)-3-cyano-4-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0636] (4S)-2-amino-3'-(4-[(3S,4S)-3-cyano-4-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0637] (4S)-2-amino-3'-(4-[(3R,4R)-3-cyano-4-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0638] (4S)-2-amino-3'-(4-[4-chloro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0639] (4S)-2-amino-3'-(4-[(3R)-3-(difluoromethyl)-3-hydroxypiperidin-1-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0640] (4S)-2-amino-3'-(4-[(3S)-3-(difluoromethyl)-3-hydroxypiperidin-1-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0641] (4S)-2-amino-3'-(4-{3-[(1S)-1-hydroxyethyl]-1H-pyrazol-1-yl}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0642] (4S)-2-amino-3'-(4-{3-[(1R)-1-hydroxyethyl]-1H-pyrazol-1-yl}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0643] (4S)-2-amino-3'-(4-[3-(hydroxymethyl)azetidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0644] (4S)-2-amino-3'-(4-[(3R)-3-(hydroxymethyl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0645] (4S)-2-amino-3'-(4-[(3S)-3-(hydroxymethyl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0646] (4S)-2-amino-3'-(4-[4-(hydroxymethyl)-2H-1,2,3-triazol-2-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0647] (4S)-2-amino-3'-(4-[4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0648] (4S)-2-amino-3'-(4-[(3R,5S)-3,5-dihydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0649] (4S)-2-amino-3'-(4-[(2S,5R)-5-hydroxy-2,5-dimethylpiperidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0650] (4S)-2-amino-3'-(4-[(2S,5S)-5-hydroxy-2,5-dimethylpiperidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0651] (4S)-2-amino-3'-[4-(3-cyano-1H-pyrazol-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0652] (4S)-2-amino-3'-(4-[8-(methoxyimino)-3-azabicyclo[3.2.1]octan-3-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0653] 2-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-N-methyl-2H-1,2,3-triazole-4-carboxamide;

[0654] 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-N-methyl-1H-1,2,3-triazole-4-carboxamide;

[0655] (4S)-2-amino-3'-[4-(4-cyano-1H-pyrazol-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0656] (4S)-2-amino-3'-(4-[4-(methoxyimino)piperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0657] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)- pyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0658] (4S)-2-amino-3'-[3-(1-methyl-1H-pyrazol-3-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0659] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-4-[(3R)-3-hydroxy-3- methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0660] 6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidine-3-carboxamide;

[0661] (4S)-2-amino-3'-[4-(4-aminopiperidin-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0662] (4S)-2-amino-3'-(4-[(1R,5S,8R)-8-amino-3-azabicyclo[3.2.1]octan-3-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0663] (4S)-2-amino-3'-(4-[(1R,5S,8S)-8-amino-3-azabicyclo[3.2.1]octan-3-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0664] (4S)-2-amino-3'-(4-[(3R,5S)-3-hydroxy-5-methoxy-3-methylpiperidin-1-yl]-1-{(1S)- 1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0665] (4S)-2-amino-3'-(4-[(6S)-6-hydroxy-5,6-dihydrocyclopenta[c]pyrazol-2(4H)-yl]-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0666] (4S)-2-amino-3'-(4-[(6R)-6-hydroxy-5,6-dihydrocyclopenta[c]pyrazol-2(4H)-yl]-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0667] (4R)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0668] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0669] (4S)-2-amino-3'-(4-[3-(hydroxymethyl)-1H-pyrrol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0670] (4S)-2-amino-3'-(3-cyano-4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0671] (4S)-2-amino-3'-(3-[1-(2-hydroxyethyl)-1H-pyrazol-3-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0672] (4S)-2-amino-3'-(4-[6-(hydroxymethyl)pyridin-2-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0673] (4S)-2-amino-3'-(4-[5-fluoro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0674] (4S)-2-amino-3'-(6-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-9-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-9H-purin-2-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0675] (4S)-2-amino-3'-(4-[(7R)-7-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0676] (4S)-2-amino-3'-(4-[(7S)-7-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0677] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- (2H3)methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0678] (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0679] (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0680] (4R)-2-amino-3'-(1-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-4-[(3R)-3-hydroxy-3- methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0681] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-4-[(3R)-3-hydroxy-3- methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0682] 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-1H-pyrazole-3-sulfonamide;

[0683] (4S)-2-amino-3'-(1-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(3R)- 3-hydroxy-3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro- 4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0684] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-7-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0685] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-7-{(1R)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0686] (4S)-2-amino-3'-(4-[(2-cyano-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0687] (4S)-2-amino-3'-(4-[(3R,5S)-5-fluoro-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0688] (4S)-2-amino-3'-(4-[(3S,5S)-5-fluoro-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0689] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0690] (4S)-2-amino-3'-(4-[(3R,5S)-3,5-dihydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0691] (4S)-2-amino-3'-(4-[(3S,4R)-3-cyano-4-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0692] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-4-[(3R)-3-hydroxy-3- methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0693] (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)- pyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0694] (4S)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0695] (4S)-2-amino-3'-(3-chloro-4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0696] (4S)-2-amino-3'-[3-cyano-4-(2-hydroxy-2-methylpropoxy)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0697] (4S)-2-amino-3'-(3-cyano-4-[3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0698] (4S)-2-amino-3'-(3-cyano-1-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-4-[(3R)-3- hydroxy-3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0699] (4S)-2-amino-3'-(3-cyano-4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1- [(2S)-pyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0700] (4S)-2-amino-3'-(4-[2-(hydroxymethyl)-1H-pyrrol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0701] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a- hexaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0702] (4R)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'- pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0703] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'- pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0704] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-pyrrolidin-2- yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2- yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0705] (4S)-2-amino-3'-[(7aR,10S)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-pyrrolidin-2- yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0706] (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-10- hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0707] (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2- yl]ethyl}-10-hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0708] (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(2R,3S)-3-fluoro-1-methylpyrrolidin-2- yl]ethyl}-10-hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0709] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-4-{(1S)-1-[(2R,3S)-3-methoxy-1- methylpyrrolidin-2-yl]ethyl}-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0710] (4S)-2-amino-3'-[(7aR)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0711] (4S)-2-amino-3'-[(7aR)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 7a,8,9,10,11,12-hexahydro-4H,7H-6-oxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0712] (4S)-2-amino-3'-[(7aR)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 7,7a,8,9,11,12-hexahydro-4H-6,10-dioxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0713] (4S)-2-amino-3'-[(7aS)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 7,7a,8,9,11,12-hexahydro-4H-6,10-dioxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0714] (4S)-2-amino-3'-[(7aR)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7a,8,11,12- tetrahydro-4H,7H,10H-6,9-dioxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0715] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-4,7a,8,9,10,11-hexahydro-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0716] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-thia-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0717] (4S)-2-amino-3'-(1-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(2- hydroxy-2-methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro- 4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0718] (4R)-2-amino-3'-(7-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-3-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-4',5',6,7-tetrahydro- 5H-spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0719] (4S)-2-amino-3'-(3-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-7-[(3R)- 3-hydroxy-3-methylpiperidin-1-yl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0720] (4R)-2-amino-3'-(3-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-7- [(3R)-3-hydroxy-3-methylpiperidin-1-yl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-4',5',6,7- tetrahydro-5H-spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0721] (4S)-2-amino-3'-(7-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-3-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-6,7-dihydro- 4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0722] (4S)-2-amino-3'-(3-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-7-[(3R)- 3-hydroxy-3-methylpiperidin-1-yl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-6,7-dihydro- 4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0723] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylazetidin- 2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2- yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0724] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1,4,4- trimethylazetidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0725] (4S)-2-amino-3'-{(7aR,10R)-4-[(2S)-1-(dimethylamino)propan-2-yl]-10-hydroxy-10- methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0726] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6,6-dioxo-4,6,7,7a,8,9,10,11-octahydro-6λ6-thia-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0727] (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(3aS,7S,7aS)-1-methyloctahydro-1H-indol-7-yl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0728] (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(3aS,7R,7aS)-1- methyloctahydropyrano[4,3-b]pyrrol-7-yl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0729] (4S)-3'-(4-hydroxy-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-2-{[(1H-pyrrol-2-yl)methyl]amino}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0730] (4S)-2-amino-3'-[(6aR,9R)-9-hydroxy-9-methyl-6-methylidene-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6,6a,7,8,9,10-hexahydro-4H-1,3,4,5,10a- pentaazaacephenanthrylen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0731] (4S)-2-amino-3'-[3-cyano-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4- (piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0732] (4S)-2-amino-3'-{4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-[(3aS,7S,7aS)-1- methyloctahydro-1H-indol-7-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0733] (4S)-2-amino-3'-[1-(2-hydroxy-2-methylpropyl)-4-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethoxy}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0734] (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(3S,7aR)-hexahydro-1H-pyrrolizin-3- yl]ethyl}-10-hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0735] (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(3S,7aS)-hexahydro-1H-pyrrolizin-3- yl]ethyl}-10-hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0736] (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(2S,3S)-3-(pyrrolidin-1- yl)butan-2-yl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen- 2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0737] (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(2R,3R)-3-(pyrrolidin-1- yl)butan-2-yl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen- 2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0738] (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(2S)-1-(pyrrolidin-1- yl)propan-2-yl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0739] (4S)-2-amino-3'-{(7aR,10R)-4-[(2S,3S)-3-(azetidin-1-yl)butan-2-yl]-10-hydroxy-10- methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0740] (4S)-2-amino-3'-{(7aR,10R)-4-[(2R,3R)-3-(azetidin-1-yl)butan-2-yl]-10-hydroxy-10- methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0741] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7-oxo-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a- hexaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0742] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-6,10-dimethyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7-oxo-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a- hexaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0743] (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1- [(2S)-pyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0744] (4S)-2-amino-3'-(3-{1-[(1r,3S)-3-hydroxycyclobutyl]-1H-pyrazol-3-yl}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0745] (4S)-2-amino-3'-(3-{1-[(1s,3R)-3-hydroxycyclobutyl]-1H-pyrazol-3-yl}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0746] (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-methyl-1H- pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0747] (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0748] (4S)-2-amino-3'-{4-[(6R)-7-amino-6-methyl-1,3,4,6-tetrahydro-5H-pyrido[3,4- f][1,4]oxazocin-5-yl]-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0749] (4S)-2-amino-3'-(3-{1-[(2S)-2-hydroxypropyl]-1H-pyrazol-3-yl}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0750] (4S)-2-amino-3'-(3-{1-[(2R)-2-hydroxypropyl]-1H-pyrazol-3-yl}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0751] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0752] (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0753] (4S)-2-amino-3'-(4-[(1R)-1-(2-aminopyridin-3-yl)ethoxy]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0754] (4S)-2-amino-3'-(3-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-3-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0755] (4S)-2-amino-3'-{(7aR,10R)-4-[(1S,2S)-2-(dimethylamino)cyclopentyl]-10-hydroxy- 10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0756] (4S)-2-amino-3'-{(7aR,10R)-4-[(1R,2R)-2-(dimethylamino)cyclopentyl]-10-hydroxy- 10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0757] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4R)-4-methyl- 2,4,6,7-tetrahydro-5H-pyrazolo[4,3-f][1,4]oxazepin-5-yl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0758] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4S)-4-methyl- 2,4,6,7-tetrahydro-5H-pyrazolo[4,3-f][1,4]oxazepin-5-yl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0759] (4S)-2-amino-3'-{(7aR,10R)-4-[(1S,2S)-2-(azetidin-1-yl)cyclopentyl]-10-hydroxy-10- methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0760] (4S)-2-amino-3'-{(7aR,10R)-4-[(1R,2R)-2-(azetidin-1-yl)cyclopentyl]-10-hydroxy-10- methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0761] (4S)-2-amino-3'-(4-[(2R)-2-(2-aminopyridin-3-yl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0762] (4S)-2-amino-3'-(4-[(2S)-2-(2-aminopyridin-3-yl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0763] (4S)-2-amino-3'-(6-[(2-aminopyridin-3-yl)methyl]-2-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0764] (4S)-2-amino-3'-[(7R)-7-(2-aminopyridin-3-yl)-6-methyl-2-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4- yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0765] (4S)-2-amino-3'-[(7S)-7-(2-aminopyridin-3-yl)-6-methyl-2-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4- yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0766] (4S)-2-amino-3'-(4-{[(1S)-1-(3-aminopyrazin-2-yl)ethyl](ethyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0767] (4S)-2-amino-3'-(4-{[(1R)-1-(3-aminopyrazin-2-yl)ethyl](ethyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0768] (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro- 4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0769] (4R)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro- 5H-spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0770] (4S)-2-amino-3'-(6-[(1R)-1-(5-methyl-1H-pyrazol-4-yl)ethyl]-2-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0771] (4S)-2-amino-3'-(6-[(1S)-1-(5-methyl-1H-pyrazol-4-yl)ethyl]-2-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0772] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4R)-4-methyl- 2,6,7,9-tetrahydropyrazolo[4,3-f][1,4]oxazocin-5(4H)-yl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0773] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4S)-4-methyl- 2,6,7,9-tetrahydropyrazolo[4,3-f][1,4]oxazocin-5(4H)-yl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0774] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4R)-4-methyl- 2,4,7,8-tetrahydropyrazolo[3,4-b][1,5]oxazocin-5(6H)-yl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0775] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4S)-4-methyl- 2,4,7,8-tetrahydropyrazolo[3,4-b][1,5]oxazocin-5(6H)-yl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0776] (4S)-2-amino-3'-(6-[1-(2-aminopyridin-3-yl)ethyl]-2-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0777] (4S)-2-amino-3'-(4-[(5R)-6-amino-5-methyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin- 4(5H)-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0778] (4S)-2-amino-3'-(4-[(5S)-6-amino-5-methyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin- 4(5H)-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;

[0779] (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0780] (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1- [(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0781] (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](2-cyanoethyl)amino}-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0782] (4S)-2-amino-3'-(4-[(6R)-7-amino-6-methyl-1,3,4,6-tetrahydro-5H-pyrido[3,4- f][1,4]oxazocin-5-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0783] (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](2,2-difluoroethyl)amino}-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0784] 2-[(7R)-4-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazol]-3'-yl]-7-methyl-2-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7,8-dihydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-6(2H)- yl]-1,4-anhydro-2,3,5-trideoxy-L-threo-pentitol;

[0785] 2-{4-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,8-dihydro-9- oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-6(2H)-yl}-1,4-anhydro-2,3,5-trideoxy-L-threo- pentitol;

[0786] 2-{4-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,8-dihydro-9- oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-6(2H)-yl}-1,4-anhydro-2,3,5-trideoxy-D-threo- pentitol;

[0787] (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(1S)-1-(tetrahydro-1H-pyrrolizin-7a(5H)-yl)ethyl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0788] (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(1R)-1-(tetrahydro-1H- pyrrolizin-7a(5H)-yl)ethyl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0789] (4S)-2-amino-3'-[(6aR,9R)-9-hydroxy-6,9-dimethyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6,6a,7,8,9,10-hexahydro-4H-1,3,4,5,10a- pentaazaacephenanthrylen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0790] (4S)-2-amino-3'-[(6S,6aR,9R)-9-hydroxy-6,9-dimethyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6,6a,7,8,9,10-hexahydro-4H-1,3,4,5,10a- pentaazaacephenanthrylen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0791] (4S)-2-amino-3'-[(6R,6aR,9R)-9-hydroxy-6,9-dimethyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6,6a,7,8,9,10-hexahydro-4H-1,3,4,5,10a- pentaazaacephenanthrylen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0792] (4S)-2-amino-3'-[2-(2-hydroxy-2-methylpropyl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-2,6,7,8-tetrahydro-1,2,3,5,6-pentaazaacenaphthylen-4-yl]-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0793] 2-{2-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-9-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-5-oxo-8,9- dihydro-7H-imidazo[4,5,1-de]pteridin-4(5H)-yl}-1,4-anhydro-2,3,5-trideoxy-L-threo- pentitol;

[0794] (4S)-2-amino-3'-(9-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(1R,5R)-3- oxabicyclo[3.1.0]hexan-1-yl]-5-oxo-4,5,8,9-tetrahydro-7H-imidazo[4,5,1-de]pteridin-2-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0795] (4S)-2-amino-3'-[4-(2-hydroxy-2-methylpropyl)-9-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-5-oxo-4,5,8,9-tetrahydro-7H-imidazo[4,5,1-de]pteridin-2-yl]-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0796] (4S)-2-amino-3'-(9-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-5-oxo-4-[(3R)- oxolan-3-yl]-4,5,8,9-tetrahydro-7H-imidazo[4,5,1-de]pteridin-2-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0797] (4R)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'- pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0798] (4S)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'- pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;

[0799] (4S)-2-amino-3'-{(7aS,10R)-10-hydroxy-10-methyl-4-[(1S)-1-(tetrahydro-1H- pyrrolizin-7a(5H)-yl)ethyl]-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0800] (4S)-2-amino-3'-{(7aS,10R)-10-hydroxy-10-methyl-4-[(1R)-1-(tetrahydro-1H- pyrrolizin-7a(5H)-yl)ethyl]-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0801] (4S)-2-amino-3'-[(7aR,10S)-4-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-10- hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0802] (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(3-oxo-2,8- diazaspiro[4.5]decan-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0803] (4S)-2-amino-3'-(4-[(2S,5R)-2-ethyl-5-hydroxy-5-methylpiperidin-1-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0804] (4S)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}(6,6,7,7-2H4)-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0805] (4S)-2-amino-3'-[(9R)-9-hydroxy-6,9-dimethyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-7,8,9,10-tetrahydro-4H-1,3,4,5,10a-pentaazaacephenanthrylen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0806] (4S)-2-amino-3'-(4-{[3-(1-hydroxyethyl)pyridin-2-yl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0807] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{1-[(2S)-1-methylazetidin-2- yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0808] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-(2H3)methyl-4-{(1S)-1-[(2S)-1- (2H3)methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0809] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6-oxo-4,6,7,7a,8,9,10,11-octahydro-6λ4-thia-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0810] (4S)-2-amino-3'-(4-[(2R,4S)-4-cyano-2-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0811] (4S)-2-amino-3'-(4-[(2R,4R)-4-cyano-2-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0812] (4S)-2-amino-3'-[(7S,7aR,10R)-10-hydroxy-7,10-dimethyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0813] (4S)-2-amino-3'-[(7R,7aR,10R)-10-hydroxy-7,10-dimethyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0814] (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](methyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0815] (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](methyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0816] (4S)-2-amino-3'-(4-{ethyl[(1R)-1-(6-hydroxypyridin-3-yl)ethyl]amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0817] (4S)-2-amino-3'-(4-{ethyl[(1S)-1-(6-hydroxypyridin-3-yl)ethyl]amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0818] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4R)-6-oxa-1- azaspiro[3.5]nonan-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0819] (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4S)-6-oxa-1- azaspiro[3.5]nonan-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0820] (4S)-2-amino-3'-[(5aR,8R)-8-hydroxy-8-methyl-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1,3,5,5a,6,7,8,9-octahydro-4-oxa-1,2,9a,10,12- pentaazabenzo[4,5]cycloocta[1,2,3-cd]inden-11-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0821] (4S)-3'-(4-{[(3S)-1-acetylpyrrolidin-3-yl](ethyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-2-amino-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0822] (4S)-3'-(4-{[(3R)-1-acetylpyrrolidin-3-yl](ethyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-2-amino-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0823] 5-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-N,N,3-trimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5- a][1,4]diazepine-2-carboxamide;

[0824] (4S)-2-amino-3'-(4-[(2R)-2-(hydroxymethyl)-2-methylazetidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0825] (4S)-2-amino-3'-(4-[(2S)-2-(hydroxymethyl)-2-methylazetidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0826] (4S)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0827] (4R)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;

[0828] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}(7,7-2H2)-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0829] (4S)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- (2H3)methylpyrrolidin-2-yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0830] (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile;

[0831] (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0832] (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](methyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile;

[0833] (4S)-2-amino-3'-[(7aR,10R)-6-ethyl-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7-oxo-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a- hexaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0834] (4S)-2-amino-3'-(4-{[(3,5-dimethyl-1H-pyrazol-4-yl)methyl](ethyl)amino}-1-{(1S)- 1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0835] (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(2S,5R)-1,5-dimethylpyrrolidin-2-yl]ethyl}- 10-hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0836] (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(2S,5S)-1,5-dimethylpyrrolidin-2-yl]ethyl}- 10-hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0837] (4S)-2-amino-3'-(4-{[(2-aminopyridin-3-yl)methyl](ethyl)amino}-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0838] (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1,5,5-trimethylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;

[0839] (4S)-2-amino-3'-(4-{[1-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; and

[0840] (4S)-2-amino-3'-(4-{[(1S)-1-(2-amino-6-methylpyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;

[0841] an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

[0842] 56. A pharmaceutical composition comprising at least one compound of any one ofclauses 1 to 55, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable excipients.

[0843] 57. A method of treating disease, such as cancer, comprising administering to a subjectin need of such treatment an effective amount of a compound of any one of clauses 1 to 55, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to clause 56.

[0844] 58. A compound of any one of clauses 1 to 55, an isotopically labeled form thereof, ora pharmaceutically acceptable salt thereof, for use in a method of treating cancer in a subject.

[0845] 59. A compound of any one of clauses 1 to 55, an isotopically labeled form thereof, ora pharmaceutically acceptable salt thereof, for treating cancer in a subject.

[0846] 60. Use of a compound of any one of clauses 1 to 55, an isotopically labeled formthereof, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating cancer in a subject.

[0847] 61. A compound of the formula

[0848] or a salt thereof, wherein R is H, methyl, isopropyl, or t-butyl.

[0849] 62. The compound of clause 61, wherein R is H.

[0850] 63. A method of comprisingcontacting with , in the presence of one or more solvents, thereby forming a salt of the formula , and

[0851] isolating the salt.

[0852] 64. The method of clause 63, wherein the one or more solvents is ethanol, hepatane, ora mixture thereof. DETAILED DESCRIPTION

[0853] Before the present disclosure is further described, it is to be understood that thisdisclosure is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.

[0854] For the sake of brevity, the disclosures of the publications cited in this specification,including patents, are herein incorporated by reference. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents, applications, published applications and other publications referred to herein are incorporated by reference in their entireties. If a definition set forth in this section is contrary to or otherwise inconsistent with a definition set forth in a patent, application, or other publication that is herein incorporated by reference, the definition set forth in this section prevails over the definition incorporated herein by reference.

[0855] As used herein and in the appended clauses, the singular forms “a,” “an,” and “the”include plural referents unless the context clearly dictates otherwise. It is further noted that the clauses may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of clause elements, or use of a “negative” limitation.

[0856] As used herein, the terms “including,” “containing,” and “comprising” are used in theiropen, non-limiting sense.

[0857] To provide a more concise description, some of the quantitative expressions givenherein are not qualified with the term “about.” It is understood that, whether the term “about” is used explicitly or not, every quantity given herein is meant to refer to the actual given value, and it is also meant to refer to the approximation to such given value that would reasonably be inferred based on the ordinary skill in the art, including equivalents and approximations due to the experimental and / or measurement conditions for such given value. Whenever a yield is given as a percentage, such yield refers to a mass of the entity for which the yield is given with respect to the maximum amount of the same entity that could be obtained under the particular stoichiometric conditions. Concentrations that are given as percentages refer to mass ratios, unless indicated differently.

[0858] Unless defined otherwise, all technical and scientific terms used herein have the samemeaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited.

[0859] Except as otherwise noted, the methods and techniques of the present embodiments aregenerally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification. See, e.g., Loudon, Organic Chemistry, Fourth Edition, New York: Oxford University Press, 2002, pp.360-361, 1084-1085; Smith and March, March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Fifth Edition, Wiley-Interscience, 2001.

[0860] Chemical nomenclature for compounds described herein has generally been derivedusing the commercially-available ACD / Labs 2022.2.3 (Advanced Chemistry Development, Inc.) or ChemDraw Professional 22.2.0.3300 (PerkinElmer Informatics, Inc.).

[0861] As used herein and in connection with chemical structures depicting the variousembodiments described herein, “*”, “**”, and “ ”, each represent a point of covalentattachment of the chemical group or chemical structure in which the identifier is shown to an adjacent chemical group or chemical structure. For example, in a hypothetical chemical structure A-B, where A and B are joined by a covalent bond, in some embodiments, the portion of A-B defined by the group or chemical structure A can be represented by ,, or , where each of “-*”, “-**”, and “ ” represents a bond to A andthe point of covalent bond attachment to B. Alternatively, in some embodiments, the portion of A-B defined by the group or chemical structure B can be represented by, ,or , where each of “” “ ”, and “ ” represents a bond to B and thepoint of covalent bond attachment to A.

[0862] It is appreciated that certain features of the disclosure, which are, for clarity, describedin the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination. All combinations of the embodiments pertaining to the chemical groups represented by the variables are specifically embraced by the present disclosure and are disclosed herein just as if each and every combination was individually and explicitly disclosed, to the extent that such combinations embrace compounds that are stable compounds (i.e., compounds that can be isolated, characterized, and tested for biological activity). In addition, all subcombinations of the chemical groups listed in the embodiments describing such variables are also specifically embraced by the present disclosure and are disclosed herein just as if each and every such sub-combination of chemical groups was individually and explicitly disclosed herein. CHEMICAL DEFINITIONS

[0863] The term “alkyl” refers to a straight- or branched-chain monovalent hydrocarbongroup. The term “alkylene” refers to a straight- or branched-chain divalent hydrocarbon group. In some embodiments, it can be advantageous to limit the number of atoms in an “alkyl” or “alkylene” to a specific range of atoms, such as C1-C20alkyl or C1-C20alkylene, C1-C12alkyl or C1-C12 alkylene, or C1-C6alkyl or C1-C6alkylene. Examples of alkyl groups include methyl (Me), ethyl (Et), n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl (tBu), pentyl, isopentyl, tert-pentyl, hexyl, isohexyl, and groups that in light of the ordinary skill in the art and the teachings provided herein would be considered equivalent to any one of the foregoing examples. Examples of alkylene groups include methylene (-CH2-), ethylene ((-CH2-)2), n- propylene ((-CH2-)3), iso-propylene ((-C(H)(CH3)CH2-)), n-butylene ((-CH2-)4), and the like. It will be appreciated that an alkyl or alkylene group can be unsubstituted or substituted as described herein. An alkyl or alkylene group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0864] The term “alkenyl” refers to a straight- or branched-chain mono-valent hydrocarbongroup having one or more double bonds. In some embodiments, it can be advantageous to limit the number of atoms in an “alkenyl” to a specific range of atoms, such as C2-C20alkenyl, C2-C12alkenyl, or C2-C6alkenyl. Examples of alkenyl groups include ethenyl (or vinyl), allyl, and but-3-en-1-yl. Included within this term are cis and trans isomers and mixtures thereof. It will be appreciated that an alkenyl can be unsubstituted or substituted as described herein. An alkenyl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0865] The term “alkynyl” refers to a straight- or branched-chain monovalent hydrocarbongroup having one or more triple bonds. In some embodiments, it can be advantageous to limit the number of atoms in an “alkynyl” to a specific range of atoms, such as C2-C20alkynyl, C2-C12alkynyl, or C2-C6alkynyl. Examples of alkynyl groups include acetylenyl (-C≡CH) and propargyl (-CH2C≡CH), but-3-yn-1,4-diyl (-C≡C-CH2CH2-), and the like. It will be appreciated that an alkynyl group can be unsubstituted or substituted as described herein. An alkynyl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0866] The term “cycloalkyl” refers to a saturated or partially saturated, monocyclic orpolycyclic mono-valent carbocycle. In some embodiments, it can be advantageous to limit the number of atoms in a “cycloalkyl” to a specific range of atoms, such as having 3 to 12 ring atoms. Polycyclic carbocycles include fused, bridged, and spiro polycyclic systems. Illustrative examples of cycloalkyl groups include monovalent radicals of the following entities:: ,In particular, a cyclopropyl moiety can be depicted by the structural formula. It will be appreciated that a cycloalkyl group can be unsubstituted or substituted as described herein. A cycloalkyl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0867] The term “halogen” or “halo” represents chlorine, fluorine, bromine, or iodine.

[0868] The term “haloalkyl” refers to an alkyl group with one or more halo substituents.Examples of haloalkyl groups include –CF3, -(CH2)F, -CHF2, -CH2Br, -CH2CF3, and -CH2CH2F.

[0869] In certain embodiments, alkenyl may be substituted. For example, the alkenyl may besubstituted with halo (e.g., fluoro). Illustratively, the alkenyl substituted with halo may be a =CHF. Illustratively, a hexahydro-1H-pyrrolizinyl moiety may be substituted by halo- substituted alkenyl, for example, a substituted hexahydro-1H-pyrrolizinyl moiety can be depicted by the structural formula.

[0870] The term “aryl” refers to a monovalent all-carbon monocyclic or fused-ring polycyclicgroup having a completely conjugated pi-electron system. In some embodiments, it can be advantageous to limit the number of atoms in an “aryl” to a specific range of atoms, such as mono-valent all-carbon monocyclic or fused-ring polycyclic groups of 6 to 14 carbon atoms (C6-C14aryl), or monovalent all-carbon monocyclic or fused-ring polycyclic groups of 6 to 10 carbon atoms (C6-C10aryl). Examples, without limitation, of aryl groups are phenyl, naphthalenyl and anthracenyl. It will be appreciated that an aryl group can be unsubstituted or substituted as described herein. An aryl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0871] The term “heterocycloalkyl” refers to a mono-valent monocyclic or polycyclic ringstructure (e.g., heterobicyclyl or bicyclic heterocyclyl) that is saturated or partially saturated having one or more non-carbon ring atoms. In some embodiments, it can be advantageous to limit the number of atoms in a “heterocycloalkyl” to a specific range of ring atoms, such as from 3 to 12 ring atoms (3- to 12-membered), or 3 to 7 ring atoms (3- to 7-membered), or 3 to 6 ring atoms (3- to 6-membered), or 4 to 6 ring atoms (4- to 6-membered), 5 to 7 ring atoms (5- to 7-membered), or 4 to 10 ring atoms (4- to 10-membered). In some embodiments, it can be advantageous to limit the number and type of ring heteroatoms in “heterocycloalkyl” or to a specific range or type of heteroatoms, such as 1 to 5 ring heteroatoms selected from nitrogen, oxygen, and sulfur. Examples, without limitations, of mono-cyclic heterocycloalkyl groups include tetrahydrofuran, pyrrolidinyl, and morpholinyl. Polycyclic ring systems include fused, bridged, and spiro systems. In some embodiments, it can be advantageous to limit the number of atoms in a bicyclic “heterocycloalkyl” to a specific range of ring atoms, such as from 5 to10 ring atoms (5- to 10-membered), or 6 to 10 ring atoms (6- to 10-membered). The ring structure may optionally contain an oxo group or an imino group on a carbon ring member or up to two oxo groups on sulfur ring members. Examples, without limitations, of fused bicyclic, bridged bicyclic, and spiro bicyclic heterocycloalkyl groups include pyrrolizinyl, 2,5- diazabicyclo[2.2.2]octanyl, and 1-oxaspiro[4.5]decanyl. Illustrative examples of heterocycloalkyl groups include monovalent radicals of the following entities: ,

[0872] A three-membered heterocycle may contain at least one heteroatom ring atom, wherethe heteroatom ring atom is a sulfur, oxygen, or nitrogen. Non-limiting examples of three- membered heterocycle groups include monovalent and divalent radicals of oxirane, azetidine, and thiirane. A four-membered heterocycle may contain at least one heteroatom ring atom, where the heteroatom ring atom is a sulfur, oxygen, or nitrogen. Non-limiting examples of four-membered heterocycle groups include monovalent and divalent radicals of azitidine, oxtenane, and thietane. A five-membered heterocycle can contain up to four heteroatom ring atoms, where (a) at least one ring atom is oxygen and sulfur and zero, one, two, or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of five-membered heterocyle groups include mono-valent and divalent radicals of pyrrolidine, tetrahydrofuran, 2, 5-dihydro-1H- pyrrole, pyrazolidine, thiazolidine, 4,5-dihydro-1H-imidazole, dihydrothiophen-2(3H)-one, tetrahydrothiophene 1,1-dioxide, imidazolidin-2-one, pyrrolidin-2-one, dihydrofuran-2(3H)-one, 1,3-dioxolan-2-one, and oxazolidin-2-one. A six-membered heterocycle can contain up to four heteroatom ring atoms, where (a) at least one ring atom is oxygen and sulfur and zero, one, two, or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of six-membered heterocycle groups include mono- valent or divalent radicals of piperidine, morpholine, 4H-1,4-thiazine, 1,2,3,4- tetrahydropyridine, piperazine, 1,3-oxazinan-2-one, piperazin-2-one, thiomorpholine, and thiomorpholine 1,1-dioxide.

[0873] A “heterobicyclyl” or “bicyclic heterocyclyl” refers to a heterocycle comprising afused, bridged, or sprio bicyclic ring system that is saturated or partially saturated having one or more non-carbon ring atoms. As used herein, “heterobicyclyl” and “bicyclic heterocyclyl” can include one heterocycle ring fused to a cycloalkyl, heterocyclyl, aryl, or heteroaryl, where the ring stem overall is saturated or partially saturated. Non-limiting examples of “heterobicyclyl” and “bicyclic heterocyclyl” include, but are not limited to, radicals of the heterobicyles

[0874] It will be appreciated that a heterocycloalkyl group (e.g., a heteromonocyclyl or aheterobicyclyl or a bicyclic heterocyclyl) can be unsubstituted or substituted as described herein. A heterocycloalkyl group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0875] The term “heteroaryl” refers to a mono-valent monocyclic, fused bicyclic, or fusedpolycyclic aromatic heterocycle (ring structure having ring atoms or members selected from carbon atoms and up to four heteroatoms selected from nitrogen, oxygen, and sulfur) that is fully unsaturated and having from 3 to 12 ring atoms per heterocycle. The term “heteroarylene” refers to a divalent monocyclic, fused bicyclic, or fused polycyclic aromatic heterocycle (ring structure having ring atoms or members selected from carbon atoms and up to four heteroatoms selected from nitrogen, oxygen, and sulfur) having from 3 to 12 ring atoms per heterocycle. In some embodiments, it can be advantageous to limit the number of ring atoms in a “heteroaryl” or “heteroarylene” to a specific range of atom members, such as 5- to 10-membered heteroaryl. In some instances, a 5- to 10-membered heteroaryl can be amonocyclic ring or fused bicyclic rings having 5- to 10-ring atoms wherein at least one ring atom is a heteroatom, such as N, O, or S. The ring structure may optionally contain an oxo group or an imino group on a carbon ring member or up to two oxo groups on sulfur ring members. Illustrative examples of 5- to 10-membered heteroaryl groups include monovalent radicals of the following entities, while examples of 5- to 10-membered heteroarylene groups include divalent radicals of the following entities, in the form of properly bonded moieties:

[0876] In some embodiments, a “monocyclic” heteroaryl can be an aromatic five- or six-membered heterocycle. A five-membered heteroaryl can contain up to four heteroatom ring atoms, where (a) at least one ring atom is oxygen and sulfur and zero, one, two, or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of five-membered heteroaryl groups include mono-valent radicals of furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole, pyrazole, imidazole, oxadiazole, thiadiazole, triazole, or tetrazole. A six-membered heteroaryl can contain up to four heteroatom ring atoms, where (a) at least one ring atom is oxygen and sulfur and zero, one, two, or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of six-membered heteroaryl groups include monovalent radicals of pyridine, pyrazine, pyrimidine, pyridazine, or triazine. A “bicyclic heteroaryl” is a fused bicyclic system comprising one heteroaryl ring fused to a phenyl or another heteroaryl ring. Non-limiting examples of bicyclic heteroaryl groups include monovalent radicals of quinoline, isoquinoline, quinazoline, quinoxaline, 1,5-naphthyridine, 1,8-naphthyridine, isoquinolin-3(2H)-one, thieno[3,2-b]thiophene, 1H-pyrrolo[2,3-b]pyridine, indazole, 1H-benzo[d]imidazole, benzo[d]oxazole, and benzo[d]thiazole.

[0877] In particular, an isoquinolin-3(2H)-onyl moiety can be depicted by the structuralformula.

[0878] In particular, a divalent pyridopyrimidine moiety can be depicted by the structuralformula.

[0879] It will be appreciated that a heteroaryl or heteroarylene group can be unsubstituted orsubstituted as described herein. A heteroaryl or heteroarylene group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0880] The term “oxo” represents a carbonyl oxygen. For example, a cyclopentyl substitutedwith oxo is cyclopentanone.

[0881] The term “substituted” means that the specified group or moiety bears one or moresubstituents. The term “unsubstituted” means that the specified group bears no substituents. Where the term “substituted” is used to describe a structural system, the substitution is meant to occur at any valency-allowed position on the system. In some embodiments, “substituted” means that the specified group or moiety bears one, two, or three substituents. In other embodiments, “substituted” means that the specified group or moiety bears one or two substituents. In still other embodiments, “substituted” means the specified group or moiety bears one substituent.

[0882] As used herein, the term “optionally substituted” refers to the replacement of one to sixhydrogen radicals in a given structure with the radical of a specified substituent including, but not limited to: deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, 4- to 10- membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, OH, -OC1-C6alkyl, OC(O)C1-C6alkyl, -OC(O)N(H or C1-C6alkyl)2, OS(O)C1-C6alkyl, OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6alkyl)2, OS(O)2N(H or C1-C6alkyl)2, -SC1-C6alkyl, S(O)C1-C6alkyl, -S(O)2C1-C6alkyl, S(O)N(H or C1-C6alkyl)2, S(O)2N(H or C1-C6alkyl)2, N(H or C1-C6alkyl)2, -N(C1-C6alkyl)C(O)-C1-C6alkyl, N(C1-C6alkyl)C(O)OC1-C6alkyl, N(C1-C6alkyl)C(O)N(H or C1-C6alkyl)2, N(C1-C6alkyl)S(O)C1-C6alkyl, -N(C1-C6alkyl)S(O)2C1-C6alkyl, -N(C1-C6alkyl)S(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)2N(H or C1-C6alkyl)2, -C(O)C1-C6alkyl, C(O)OC1-C6alkyl, C(O)N(H or C1-C6alkyl)2, -P(H or C1-C6alkyl)2, -P(O)(H or C1-C6alkyl)2, -P(O)2(H or C1-C6alkyl)2, -P(O)N(H or C1-C6alkyl)2, P(O)2N(H or C1-C6alkyl)2,-P(O)OC1-C6alkyl, P(O)2OC1-C6alkyl, CN, or -NO2. “Optionally substituted” refers to the replacement of one to four hydrogen radicals in a given structure with the substituents mentioned above. For example, one to three hydrogen radicals can be replaced by the substituents as mentioned above. It is understood that the substituent can be further substituted.

[0883] Any formula depicted herein is intended to represent a compound of that structural formula as well as certain variations or forms. For example, a formula given herein is intended to include a racemic form, or one or more enantiomeric, diastereomeric, or geometric isomers, or a mixture thereof. Additionally, any formula given herein is intended to refer also to a hydrate, solvate, or polymorph of such a compound, or a mixture thereof.

[0884] Any formula given herein is also intended to represent unlabeled forms as well as isotopically labeled forms of the compounds. Certain compounds described herein contain an isotopic label. It should be understood that isotopically labeled compounds thereof is meant to encompass further isotopic labels as described herein. Isotopically labeled compounds have structures depicted by the formulas given herein except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into compounds of the disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, chlorine, and iodine, such as2H,3H,11C,13C,14C,15N,18O,17O,31P,32P,35S,18F,36Cl, and125I, respectively. Such isotopically labelled compounds are useful in metabolic studies (preferably with14C), reaction kinetic studies (with, for example2H or3H), detection or imaging techniques [such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT)] including drug or substrate tissue distribution assays, or in radioactive treatment of patients. Further, substitution with heavier isotopes such as deuterium (i.e.,2H) may afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements. Isotopically labeled compounds of this disclosure and prodrugs thereof can generally be prepared by carrying out the procedures disclosed in the schemes or in the examples and preparations described below by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent.

[0885] As described herein, a compound may be of a particular formula (e.g., of Formula (I)- (XXVI)), an isotopically labeled form thereof (e.g., an isotopically labeled form of the compound of Formula (I)-(XXVI)), or a pharmaceutically acceptable salt thereof (e.g., a pharmaceutically acceptable salt of the compound of Formula (I)-(XXVI) or a pharmaceutically acceptable salt of the isotopically labeled form of the compound of Formula (I)-(XXVI)). Certain compounds described herein contain one or more isotopic label. It willbe understood that isotopically labeled compounds as described herein may include one or more isotopic labels that may be the same or different.

[0886] Certain chemical entities of Formula (I)-(XXVI) may be depicted in two or more tautomeric forms. Any and all alternative tautomers are included within the scope of these formulas, and no inference should be made as to whether the chemical entity exists as the tautomeric form in which it is drawn. It will be understood that the chemical entities described herein, and their constituent rings A, B, etc. can exist in different tautomeric forms. It will be readily appreciated by one of skill in the art that because of rapid interconversion, tautomers can generally be considered to be the same chemical compound. Examples of tautomers include but are not limited to enol-keto tautomers, amine-imine tautomers, and the like.

[0887] In particular, a ring option of isoquinolin-3(2H)-oneylene can exist as the following tautomers .

[0888] The nomenclature “(ATOM)i-(ATOM)j” with j > i, when applied herein to a class of substituents, is meant to refer to embodiments of this disclosure for which each and every one of the number of atom members, from i to j including i and j, is independently realized. By way of example, the term C1-C3refers independently to embodiments that have one carbon member (C1), embodiments that have two carbon members (C2), and embodiments that have three carbon members (C3).

[0889] The disclosure also includes pharmaceutically acceptable salts of the compounds represented by Formula (I)-(XVIII), preferably of those described above and of the specific compounds exemplified herein, and pharmaceutical compositions comprising such salts, and methods of using such salts.

[0890] A “pharmaceutically acceptable salt” is intended to mean a salt of a free acid or base of a compound represented herein that is non-toxic, biologically tolerable, or otherwise biologically suitable for administration to the subject. See, generally, S.M. Berge, et al., “Pharmaceutical Salts,” J. Pharm. Sci., 1977, 66, 1-19. Preferred pharmaceutically acceptable salts are those that are pharmacologically effective and suitable for contact with the tissues of subjects without undue toxicity, irritation, or allergic response. A compound described herein may possess a sufficiently acidic group, a sufficiently basic group, both types of functional groups, or more than one of each type, and accordingly react with a number of inorganic or organic bases, and inorganic and organic acids, to form a pharmaceutically acceptable salt.,” wherein “W ” is an inorganic counter ion (e.g., an inorganic anion) or an organic counterion (e.g., an organic anion). In certain embodiments, W is an anion that is complexed witha cation of a compound of the disclosure to form a pharmaceutically acceptable salt.

[0891] It will be understood that the chemical entities described herein, can exist as a salt of a free acid or base of a compound represented herein and an inorganic or organic counter ion. Illustratively, the salt can be formed during the manufacture of the compound (e.g., a salt or a pharmaceutically acceptable salt) or can substituted to a salt for further manufacture, formulation, or administration reasons. As illustrated herein, certain compounds include a “W ,” wherein “W ” is an inorganic counter ion (e.g., an inorganic anion) or an organiccounter ion (e.g., an organic anion). In certain embodiments, W is an anion that iscomplexed with a cation of a compound of the disclosure to form a pharmaceutically acceptable salt.

[0892] The term “inorganic counter ion” represents an inorganic ion that accompanies an ionic species in order to maintain electric neutrality. An inorganic counter ion may represent an anion or cation. An inorganic counterion may accompany a free acid or base of a compound represented herein. An inorganic ion may form by a reaction of an inorganic base or inorganic acid and a compound described herein that possesses a sufficiently acidic group, a sufficiently basic group, both types of functional groups, or more than one of each type.

[0893] The term “organic counter ion” represents an organic counter ion that accompanies an ionic species in order to maintain electric neutrality. The organic ion may represent an anion or cation. An organic counter ion may accompany a free acid or base of a compound represented herein. An organic ion may form by a reaction of an organic base or organic acid and a compound described herein that possesses a sufficiently acidic group, a sufficiently basic group, both types of functional groups, or more than one of each type.

[0894] Examples of pharmaceutically acceptable salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogen-phosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne-1,4-dioates, hexyne-1,6-dioates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, sulfonates, methylsulfonates, propylsulfonates, besylates, xylenesulfonates, naphthalene-1-sulfonates, naphthalene-2- sulfonates, phenylacetates, phenylpropionates, phenylbutyrates, citrates, lactates, γ- hydroxybutyrates, glycolates, tartrates, and mandelates. Lists of other suitable pharmaceutically acceptable salts are found in Remington's Pharmaceutical Sciences, 17th Edition, Mack Publishing Company, Easton, Pa., 1985.

[0895] For a compound of Formula (I)-(XXVI) that contains a basic nitrogen, a pharmaceutically acceptable salt may be prepared by any suitable method available in the art, for example, treatment of the free base with an inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, nitric acid, boric acid, phosphoric acid, and the like, or with an organic acid, such as acetic acid, phenylacetic acid, propionic acid, stearic acid, lactic acid, ascorbic acid, maleic acid, hydroxymaleic acid, isethionic acid, succinic acid, valeric acid, fumaric acid, malonic acid, pyruvic acid, oxalic acid, glycolic acid, salicylic acid, oleic acid, palmitic acid, lauric acid, a pyranosidyl acid, such as glucuronic acid or galacturonic acid, an alpha-hydroxy acid, such as mandelic acid, citric acid, or tartaric acid, an amino acid, such as aspartic acid or glutamic acid, an aromatic acid, such as benzoic acid, 2-acetoxybenzoic acid, naphthoic acid, or cinnamic acid, a sulfonic acid, such as laurylsulfonic acid, p- toluenesulfonic acid, methanesulfonic acid, or ethanesulfonic acid, or any compatible mixture of acids such as those given as examples herein, and any other acid and mixture thereof that are regarded as equivalents or acceptable substitutes in light of the ordinary level of skill in this technology.

[0896] The disclosure also relates to pharmaceutically acceptable prodrugs of the compounds of Formula (I)-(XXVI), and treatment methods employing such pharmaceutically acceptable prodrugs. The term “prodrug” means a precursor of a designated compound that, following administration to a subject, yields the compound in vivo via a chemical or physiological process such as solvolysis or enzymatic cleavage, or under physiological conditions (e.g., a prodrug on being brought to physiological pH is converted to the compound of Formula (I)-(XXVI)).

[0897] A “pharmaceutically acceptable prodrug” is a prodrug that is non-toxic, biologically tolerable, and otherwise biologically suitable for administration to the subject. Illustrativeprocedures for the selection and preparation of suitable prodrug derivatives are described, for example, in “Design of Prodrugs,” ed. H. Bundgaard, Elsevier, 1985.

[0898] The present disclosure also relates to pharmaceutically active metabolites of compounds of Formula (I)-(XXVI), and uses of such metabolites in the methods of the disclosure. A “pharmaceutically active metabolite” means a pharmacologically active product of metabolism in the body of a compound of Formula (I)-(XXVI) or salt thereof. Prodrugs and active metabolites of a compound may be determined using routine techniques known or available in the art. See, e.g., Bertolini et al., J. Med. Chem.1997, 40, 2011-2016; Shan et al., J. Pharm. Sci. 1997, 86 (7), 765-767; Bagshawe, Drug Dev. Res.1995, 34, 220-230; Bodor, Adv. Drug Res.1984, 13, 255-331; Bundgaard, Design of Prodrugs (Elsevier Press, 1985); and Larsen, Design and Application of Prodrugs, Drug Design and Development (Krogsgaard- Larsen et al., eds., Harwood Academic Publishers, 1991).

[0899] As used herein, the term “KRAS inhibitor” includes, but is not limited to, a compound that is capable of inhibiting the protein encoded by the KRAS gene, called K-Ras, that is involved in the RAS / MAPK signaling pathway. The terms KRAS gene, K-Ras, and RAS / MAPK signaling pathway will be known and understood by one of skill in the art. It will be appreciated that KRAS mutations occur in approximately one in seven of all human metastatic cancers, and that those mutations can occur in a variety of locations in the KRAS gene coding sequence. KRAS mutations primarily occur in KRAS codons 12 and 13, and also occur in codons 18, 61, 117, and 146 at low frequencies and have distinct effects on tumor cell signaling based on the codon and missense mutation. Examples of KRAS mutations include, but are not limited to KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12R, KRAS G12S, KRAS G13C, KRAS G13D, KRAS A18D, KRAS Q61H, KRAS K117N, and the like. It will be understood by a person having ordinary skill in the art that reference to a inhibiting of KRAS mutations, such as KRAS G12D refers to inhibiting the protein encoded by the KRAS G12D gene, having a coding sequence (e.g. a guanine to adenine substitution, at position 35 on codon 12 of the KRAS coding sequence) that produces a K-Ras G12D protein, where a glycine at position 12 of the protein sequence is replaced by am aspartic acid. REPRESENTATIVE EMBODIMENTS

[0900] In some embodiments, the disclosure relates to a compound of the formula I,

[0901] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, R1,R2,R3,R4,R5, R6, X, X1, X2, X3, Y, m1, m2, m3, n1, and n2 are as described herein.

[0902] In some embodiments, the disclosure provides a compound of the formula II,

[0903] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, R1, R2, R3, R4, R5, R6, X, Y, m1, m2, m3, n1, and n2 are as described herein.

[0904] In some embodiments, the disclosure provides a compound of the formula III,

[0905] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, R1, R2, R3, R4, R6, X, Y, Y1, Y2, m1, m2, n1, and n2 are as described herein.

[0906] In some embodiments, the disclosure provides a compound of the formula IV,

[0907] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R6, X, Y1, Y2, m1, m2, n1, and n2 are as described herein.

[0908] In some embodiments, the disclosure provides a compound of the formula V,V

[0909] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R3,R4, R6, X, Y,Y1, Y2, Z, Z1, Z2, Z3, n1, and n2 are as described herein.

[0910] In some embodiments, the disclosure provides a compound of the formula VI,

[0911] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R3,R4, R6, X, Y,Y1, Y2, Z, Z1, Z2, Z3, n1, and n2 are as described herein.

[0912] In some embodiments, the disclosure provides a compound of the formula VII,

[0913] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R5, R6, X, m1, m2, m3, n1, and n2 are as described herein.

[0914] In some embodiments, the disclosure provides a compound of the formula VIII,VIII

[0915] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R5, R6, X, m1, m2, m3, n1, and n2 are as described herein.

[0916] In some embodiments, the disclosure provides a compound of the formula IX,

[0917] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R6, X, Y1, Y2, m1, m2, m3, n1, and n2 are as described herein.

[0918] In some embodiments, the disclosure provides a compound of the formula X,

[0919] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R1,R2,R3,R4,R6, X, Y1, Y2, m1, m2, m3, n1, and n2 are as described herein.

[0920] In some embodiments, the disclosure provides a compound of the formula XI,

[0921] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R3,R4, R6, X, Y1,Y2, Z, Z1, Z2, Z3, n1, and n2 are as described herein.

[0922] In some embodiments, the disclosure provides a compound of the formula XII,

[0923] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R3,R4, R6, X, Y1,Y2, Z, Z1, Z2, Z3, n1, and n2 are as described herein.

[0924] In another aspect, the disclosure provides a compound of the formula XIII,

[0925] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B,R3,R4, R6, Y1,Y2, Z, Z1, Z2, Z3, Z4, Z5, Z6, n1, and n2 are as described herein.

[0926] In another aspect, the disclosure provides a compound of the formula XIV,

[0927] or a pharmaceutically acceptable salt thereof, wherein ring A,R1,R2,R3,R4, R6, Y1,Y2, m1, m2, n1, and n2 are as described herein.

[0928] In another aspect, the disclosure provides a compound of the formula XV,

[0929] or a pharmaceutically acceptable salt thereof, wherein ring A,R1,R2,R3,R4, R6, Y1,Y2, m1, m2, n1, and n2 are as described herein.

[0930] In another aspect, the disclosure provides a compound of the formula XVI,

[0931] or a pharmaceutically acceptable salt thereof, wherein ring A,R1,R2,R3,R4, R6, Y1,Y2, m1, m2, n1, and n2 are as described herein.

[0932] In another aspect, the disclosure provides a compound of the formula XVII,

[0933] or a pharmaceutically acceptable salt thereof, wherein ring A,R1,R2,R3,R4, R6, Y1,Y2, m1, m2, n1, and n2 are as described herein.

[0934] In another aspect, the disclosure provides a compound of the formula XVIII,XVIII

[0935] or a pharmaceutically acceptable salt thereof, wherein ring A,R2,R3,R4, R6, Y1, Y2,m2, n1, and n2 are as described herein.

[0936] In another aspect, the disclosure provides a compound of the formula XVIX,XVIX

[0937] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B1, ring B2,R1,R2,R3, R4, R5, R6, X1, X2, X3, Y, m1, m2, m3, n1, and n2 are as described herein.

[0938] In another aspect, the disclosure provides a compound of the formula XX,

[0939] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B1, ring B2, ring C,R1, R2, R3, R4, R5, R6, X1, X2, X3, Y, m1, m2, m3, n1, and n2 are as described herein.

[0940] In another aspect, the disclosure provides a compound of the formula XXI

[0941] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, Ra’, Rb’,R1,R2,R3, R4, R5, R6, X, X1, X2, X3, Y, m1, m2, m3, n1, and n2 are as described herein.

[0942] In another aspect, the disclosure provides a compound of the formula XXII

[0943] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, Ra’, Rb’,R1,R2,R3, R4, R5, R6, X, Y, m1, m2, m3, n1, and n2 are as described herein.

[0944] In another aspect, the disclosure provides a compound of the formula XXIIIXIII

[0945] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, Ra’, Rb’,R1,R2,R3, R4, R5, R6, X, Y, Y1, Y2, m1, m2, m3, n1, and n2 are as described herein.

[0946] In another aspect, the disclosure provides a compound of the formula XXIVXXIV

[0947] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, Ra’, Rb’,R1,R2,R3, R4, R5, R6, X, Y, Y1, Y2, m1, m2, m3, n1, and n2 are as described herein.

[0948] In another aspect, the disclosure provides a compound of the formula XXVXXV

[0949] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, Ra’, Rb’,R1,R2,R3, R4, R5, R6, X, Y1, Y2, m1, m2, m3, n1, and n2 are as described herein.

[0950] In another aspect, the disclosure provides a compound of the formula XXVIXXVI

[0951] or a pharmaceutically acceptable salt thereof, wherein ring A, ring B, Ra’, Rb’,R1,R2,R3, R4, R5, R6, X, Y1, Y2, m1, m2, m3, n1, and n2 are as described herein.

[0952] In some embodiments, at least one hydrogen atom in the compound of the Formula (I)-(XXVI) is substituted by a deuterium. In some embodiments, at least one hydrogen atom in ring A, ring B, R1, R2, R3, R4, R5, R6, or R7in the compound of the Formula (I)-(XXVI) is substituted by a deuterium.

[0953] In some embodiments, each of X1 and X3 is independently an -O-, -S-, -S(O)2-, or-CH2-, and X2is a bond, -O-, -S-, -S(O)2-, or -CH2-, provided that no more than one of X1, X2, and X3is a -O-, -S-, or -S(O)2-. In certain embodiments, each of X1, X2, and X3is -CH2-. In some embodiments, X2is a bond and X1and X3are each independently -CH2-. In some embodiments, each of X1and X3is independently an -O-, -S-, -S(O)2-, or -CH2-, and X2is a bond, -O-, -S-, -S(O)2-, - CH2CH2-, or -CH2-, provided that no more than one of X1, X2, and X3is a -O-, -S-, or -S(O)2-.

[0954] In some embodiments, each of Z, Z2, Z3, Z5, and Z6 is independently N, CH, CR1, orCR2, Z1 is N, C, CH, CR1, or CR2, and Z4 is C or N. In some embodiments, each of Z and Z1 isindependently N, CH, or CR1, and each of Z2and Z3is independently N, CH, or CR2. In some embodiments, each of Z1and Z2is independently N, CH, or CR1. In some embodiments, Z is N. In some embodiments, Z1is N. In some embodiments, Z1is C. In some embodiments, Z1is CH. In some embodiments, Z1is CR1. In some embodiments, Z1is CR1. In some embodiments, Z2is N. In some embodiments, Z2is CH. In some embodiments, Z2is CR1. In some embodiments, Z2is CR2. In some embodiments, Z1is N and Z2is CH or CR1. In some embodiments, Z2is N and Z1is CH or CR1. In some embodiments, Z is N, Z1is CH, CR1, or CR2, and Z2is CH, CR1, or CR2. In some embodiments, Z is N, Z1is CH, CR1, or CR2, Z2is CH, CR1, or CR2, and Z3is N. In some embodiments, Z is N, Z1is C, Z2is CH, CR1, or CR2, Z3is N, and Z4is N. In some embodiments, Z is N, Z1is C, or CR2, Z2is CH, CR1, or CR2, Z3is N, and Z4is C. In some embodiments, Z is N, Z1is C, Z2is CH, CR1, or CR2, Z3is N, and Z5is N. In some embodiments, Z is N, Z1is C, Z2is CH, CR1, or CR2, Z3is N, and Z6is N. In some embodiments, Z is N, Z1is C, Z2is CH, CR1, or CR2, Z3is N, Z4is N, and Z5is N. In some embodiments, Z is N, Z1is C, Z2is CH, CR1, or CR2, Z3is N, Z4is N, and Z6is N. In some embodiments, Z is N, Z1is C, Z2is CH, CR1, or CR2, Z3is N, Z4is N, Z5is N, and Z6is N. In some embodiments, Z is N, Z1is C, Z2is CH, CR1, or CR2, Z3is N, Z4is N, Z5is CH, CR1, or CR2, and Z6is N. In some embodiments, Z is N, Z1is C, Z2is CH, CR1, or CR2, Z3is N, Z4is N, Z5is CH, CR1, or CR2, and Z6is CH, CR1, or CR2. In some embodiments, Z is N, Z1is C, Z2is CH, CR1, or CR2, Z3is N, Z4is N, Z5is N, and Z6is CH, CR1, or CR2. In some embodiments, Z is N, Z1is C, Z2is CH, CR1, or CR2, Z3is N, Z4is CH, CR1, or CR2, Z5is N, and Z6is N.

[0955] In some embodiments, Z is N, Z1is C, Z2is CH or CR2, Z3is N, Z4is N, Z5is N, and Z6is N. In some embodiments, Z is N, Z1is C, Z2is CH or CR2, Z3is N, Z4is N, Z5is CH or CR1, and Z6is N. In some embodiments, Z is N, Z1is C, Z2is CH or CR2, Z3is N, Z4is N, Z5is CH or CR2, and Z6is CH or CR2. In some embodiments, Z is N, Z1is C, Z2is CH or CR2, Z3is N, Z4is N, Z5is N, and Z6is CH or CR1. In some embodiments, Z is N, Z1is C, Z2is CH or CR2, Z3is N, Z4is CH or CR1, Z5is N, and Z6is N.

[0956] In some embodiments, X is -O-, -S-, or -NR7-. In some embodiments, X is -O-. In some embodiments, X is -NR7-. In some embodiments, R7is H, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10- membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkylORe, -C1-C6alkyl-SRe, -C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re,-OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2. In some embodiments, an R1and R7, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0957] In some embodiments, Y is -O-, -S-, -S(O)-, -S(O)2-, -NH-, -CH2-, -CH2CH2-, -OCH2-,-CH2O-, -SCH2-, -CH2S-, -S(O)CH2-, -CH2S(O)-, -S(O)2CH2-, -CH2S(O)2-, -NHCH2-, or -CH2NH-. In some embodiments, Y is O and the compound comprises a portion of the formula. In some embodiments, Y is -OCH2-, and the compound comprises aportion of the formulasome embodiments, Y is -CH2CH2-, and the compound comprises a portion of the formula.

[0958] In some embodiments, Y1 and Y2 are each independently N, O, S, CH, CR5, or C,provided that at least one of Y1and Y2is N, O, or S and only one of Y1and Y2is O or S. In some embodiments, Y1is O. In some embodiments, Y1is N. In some embodiments, Y2is O. In some embodiments, Y2is N. In some embodiments, Y1is N and Y2is O. In some embodiments, Y1is O and Y2is N.

[0959] In some embodiments, eachR1, when present, when bonded to carbon is independentlydeuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10- membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; each R1, when present, when bonded to nitrogen is independently deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -C(O)Ra, -C(O)ORa, or -C(O)NRaRb; or two R1, when present, taken together with the atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl ora 5- to 10-membered heteroaryl; or anR1and anR2, when present, taken together with theatoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, or a 5- to 10-membered heteroaryl; or an R1and R7, when present, takentogether with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), and 4- to 10- membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0960] In some embodiments,R1is optionally substituted C1-C6 alkyl (e.g., methyl or ethyl,which can be substituted by hydroxy or halo), 5- to 10-membered heteroaryl (e.g., pyrazolyl, which can be substituted by -C(O)NHC1-C6alkyl, -C(O)NH-4-10 membered heterocycloalkyl, or 4- to 10-membered heterocycloalkyl, each of which can be further optionally substituted by C1-C6alkyl such as methyl), 4- to 10-membered heterocycloalkyl (e.g., a 6-membered heterocycloalkyl such as piperidine or piperazine, which can be substituted by hydroxy, C1-C6alkyl such as methyl, C3-C6cycloalkyl either through a single bond or through spiro ring formation, or 4- to 10-membered heterocycloalkyl, each of which can be further optionally substituted by halo). In some embodiments, an R1is -NRaRb, wherein one of Raor Rbis a C1-C6-alkylene(5- to 10-membered heteroaryl), such as a 1-ethyl-1-(6-amino-2-pyridyl) or a substituted or unsubstituted C1-C6-alkyl, such as a difluoroeth-1-yl and the other of Raand Rbis an H or a C1-C6-alkyl. In some embodiments, R1is -NHC1-C6alkyl (e.g., methyl or ethyl, which can be substituted by 5- to 10-membered heteroaryl, such as pyrazolyl or pyridyl, each of which can be further optionally substituted by -N(H or C1-C6alkyl)2, such as –NH2). In some embodiments, R1is fluoro, chloro, methyl, ethyl, iso-propyl, hydroxyethyl, difluoromethyl, methylamino, dimethylamino, 2,2-difluoroethylamino, N-methyl-N-2,2- difluoroethylamino,,, , ,,, , or an R1and an R2or two R1combine to form cyclopropyl. In some embodiments, R1is fluoro, chloro, methyl, ethyl, iso-propyl, hydroxyethyl, difluoromethyl, methylamino, dimethylamino, 2,2-difluoroethylamino, N-methyl-N-2,2-difluoroethylamino, ,,,or anR1and2anRortwo R1combine to form cyclopropyl.

[0961] In some embodiments, eachR2, when present, when bonded to carbon is independentlydeuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10- membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; each R2, when present, when bonded to nitrogen is independently deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, -C(O)Ra, -C(O)ORa, or -C(O)NRaRb; or two R2, when present, taken together with the atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; or anR2and anR3, whenpresent, taken together with the atoms to which they are attached, combine to form a C6-C8cycloalkyl or 6- to 8-membered heterocycloalkyl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl, C6-C8cycloalkyl, and 6- to 8-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf,-NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0962] In some embodiments, R2is optionally substituted C1-C6alkyl (e.g., methyl or ethyl, which can be substituted by hydroxy or halo), 5- to 10-membered heteroaryl (e.g., pyrazolyl, which can be substituted by -C(O)NHC1-C6alkyl, or -C(O)NH-4-10 membered heterocycloalkyl, or 4- to 10-membered heterocycloalkyl, each of which can be further optionally substituted by C1-C6alkyl such as methyl), 4- to 10-membered heterocycloalkyl (e.g., a 6-membered heterocycloalkyl such as piperidine or piperazine, which can be substituted by hydroxy, C1-C6alkyl such as methyl, C3-C6cycloalkyl, or 4- to 10-membered heterocycloalkyl, each of which may be further optionally substituted by halo). In certain embodiments, an R2and an R3taken together with the atoms to which they are attached, combine to form a C6-C8cycloalkyl or 6- to 8-membered heterocycloalkyl. For example, an R2and an R3taken together with the atoms to which they are attached, can combine to form a C6-C8cycloalkyl such as cyloheptyl, which can be optionally substituted. In some embodiments, R2is -NHC1-C6alkyl (e.g., methyl or ethyl, which can be substituted by 5- to 10-membered heteroaryl, such as pyrazolyl or pyridyl, each of which can be further optionally substituted by -N(H or C1-C6alkyl)2, such as –NH2). In some embodiments, each R3and R4, when present, is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -ORc, -OC(O)Rc, -OC(O)NRcRd, -OC(=NRc)NRcRd, -OS(O)Rc, -OS(O)2Rc, -OS(O)NRcRd, -OS(O)2NRcRd, -SRc, -S(O)Rc, -S(O)2Rc, -S(O)NRcRd, -S(O)2NRcRd, -NRcRd, -NRcC(O)Rd, -NRcC(O)ORd, -NRcC(O)NRcRd, -NRcC(=NRd)NRcRd, -NRcS(O)Rd, -NRcS(O)2Rd, -NRcS(O)NRcRd, -NRcS(O)2NRcRd, -C(O)Rc, -C(O)ORc, -C(O)NRcRd, -C(=NRc)NRcRd, -PRcRd, -P(O)RcRd, -P(O)2RcRd, -P(O)NRcRd, -P(O)2NRcRd, -P(O)ORc, -P(O)2ORc, -CN, or -NO2; or two R3or two R4, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6cycloalkyl or a 4- to 10-membered heterocycloalkyl; or two R3or two R4, when present, taken together with the carbon atom to which they are attached combine to form an oxo group or a C2-C6alkenyl group; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf,-NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0963] In some embodiments,R2is optionally substituted C1-C6 alkyl (e.g., methyl or ethyl,which can be substituted by hydroxy or halo), 5- to 10-membered heteroaryl (e.g., pyrazolyl, which can be substituted by -C(O)NHC1-C6alkyl, -C(O)NH-4-10 membered heterocycloalkyl, or 4- to 10-membered heterocycloalkyl, each of which can be further optionally substituted by C1-C6alkyl such as methyl), 4- to 10-membered heterocycloalkyl (e.g., a 6-membered heterocycloalkyl such as piperidine or piperazine, which can be substituted by hydroxy, C1-C6alkyl such as methyl, C3-C6cycloalkyl either through a single bond or through spiro ring formation, or 4- to 10-membered heterocycloalkyl, each of which can be further optionally substituted by halo). In some embodiments, an R2is -NRaRb, wherein one of Raor Rbis a C1-C6-alkylene(5- to 10-membered heteroaryl), such as a 1-ethyl-1-(6-amino-2-pyridyl) or a substituted or unsubstituted C1-C6-alkyl, such as a difluoroeth-1-yl and the other of Raand Rbis an H or a C1-C6-alkyl. In some embodiments, R2is -NHC1-C6alkyl (e.g., methyl or ethyl, which can be substituted by 5- to 10-membered heteroaryl, such as pyrazolyl or pyridyl, each of which can be further optionally substituted by -N(H or C1-C6alkyl)2, such as –NH2). In some embodiments, R2is fluoro, chloro, methyl, ethyl, iso-propyl, hydroxyethyl, difluoromethyl, methylamino, dimethylamino, 2,2-difluoroethylamino, N-methyl-N-2,2- difluoroethylamino, , , , , , , , , , , , , , , , , , , ,, or an R2and an R1or two R2combine to form cyclopropyl. In some embodiments, R2is, , , ,In some embodiments, R2is fluoro, chloro, methyl, ethyl,iso-propyl, hydroxyethyl, difluoromethyl, methylamino, dimethylamino, 2,2- difluoroethylamino, N-methyl-N-2,2-difluoroethylamino,,or anR2and anR1or twoR2combine to formcyclopropyl.

[0964] In some embodiments, n1 is 0, 1, 2, 3, or 4. In some embodiments, n1 is 0, 1, 2, or 3.In some embodiments, n1 is 0, 1, or 2. In some embodiments, n1 is 1, 2, or 3. In some embodiments, n1 is 1 or 2. In some embodiments, n1 is 0 or 1. In some embodiments, n1 is 0 or 2. In some embodiments, n1 is 0.

[0965] In some embodiments, n2 is 0, 1, 2, 3, or 4. In some embodiments, n1 is 0, 1, 2, or 3.In some embodiments, n2 is 0, 1, or 2. In some embodiments, n2 is 1, 2, or 3. In some embodiments, n2 is 1 or 2. In some embodiments, n2 is 0 or 1. In some embodiments, n2 is 0.

[0966] In some embodiments, m1 is 0, 1, or 2. In some embodiments, m1 is 0. In someembodiments, m1 is 1. In some embodiments, m1 is 2.

[0967] In some embodiments, m2 is 0, 1, or 2. In some embodiments, m2 is 0. In someembodiments, m2 is 1. In some embodiments, m2 is 2.

[0968] In some embodiments, m3 is 0 or 1. In some embodiments, m3 is 0. In someembodiments, m3 is 1.

[0969] In some embodiments, ring A is a 5- or 6-membered heteroaryl. In some embodiments,ring A is 5-membered heteroaryl. In some embodiments, ring A is an oxazole. In some embodiments, ring A is selected from the group consisting ofand, wherein the singledenotes a point of attachment to form the bicycle and thedouble “denote the point of attachment to ring B.

[0970] In some embodiments, ring B is a 5- to 10-membered heteroaryl or a 7- to 11-memberedheterobicyclyl. In some embodiments, ring B is a 5- to 10-membered heteroaryl and may contain at least one or at least two heteroatoms (e.g., nitrogen). In some embodiments, ring B i wherein each of Z and Z1is independently N, CH, o1r CR , and each of Z2and Z3is independently N, CH, or CR2. In some embodiments ring B is a 6-membered heteroaryl, for example pyrimidine and may be of the formulaoror a pyridine and may be of the formulawherein the represent connection points to the remaining portions of the compound. In some embodiments, ring B is a bicyclic heteroaryl, for example,or, wherein therepresent connection points to the remaining portions of the compound.

[0971] In some embodiments, ring B is a 7- to 11-membered heterobicycle. For example, insome embodiments ring B is. For example, when m1 or m2, or both m1 and m2, is greater than 0, ring B can be of the formular, wherein the represent connection points to the remaining portions of the compound.

[0972] In some embodiments, ring B is of the formula,

[0973] wherein “ ” is a point of covalent attachment to ring A.

[0974] In some embodiments, ring B is of the formula

[0975] wherein “ ” is a point of covalent attachment to ring A.

[0976] In some embodiments, ring B is of the formula,, , , , , ,,,

[0977] wherein “ ” is a point of covalent attachment to ring A.

[0978] In some embodiments, the compound comprises a portion of the formula,

[0979] wherein “ ” is a point of covalent attachment to ring A.

[0980] In some embodiments, the compound comprises a portion of the formula,,

[0981] wherein “ ” is a point of covalent attachment to ring A.

[0982] In some embodiments, ring B1 and ring B2 together form 9 to 10-membered heteroarylor 7- to 11-membered heterobicyclyl, wherein each of R1and R2, if present, can be on ring B1 or ring B2.

[0983] In some embodiments, ring C is C3-C6 cycloalkyl, 4- to 10-membered heterocycloalkylor a 5- to 10-membered heteroaryl, wherein each hydrogen atom in C3-C6cycloalkyl, 5- to 10- membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl- C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[0984] In some embodiments, the compound comprises a portion having the formula,r, wherein “ ” is a point of covalent attachment to ring A.

[0985] In some embodiments, the compound comprises a portion of the formula,wherein “ ” is a point of covalent attachment to ring A.

[0986] In some embodiments, X is -NR7- and anR1and R7, taken together with the atoms towhich they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10- membered heteroaryl, each of which is optionally substituted. In some embodiments, the compound comprises a portion of the formula ,wherein “ ” is a point of covalent attachment to ring A. In some embodiments, thecompound comprises a portion (e.g., a ring B) having the formula,,wherein “ ” is a point of covalent attachment to ring A.

[0987] In some embodiments, the compound comprises a portion (e.g., a ring B) having theformula ,, , , , ,,,wherein “ ” is a point of covalent attachment to ring A.

[0988] In some embodiments, the compound comprises a portion (e.g., a ring B) having theformula ,, , , , ,,wherein “ ” is a point of covalent attachment to ring A.

[0989] In some embodiments, the compound comprises a portion (e.g., a ring B) having theformula,,,,,,,,,,,,,

[0990] wherein “ ” is a point of covalent attachment to ring A.

[0991] In some embodiments, the compound comprises a portion having the formula, ,, , , ,,

[0992] wherein “ ” is a point of covalent attachment to ring A.

[0993] In some embodiments, the compound comprises a portion having the formula,,

[0994] wherein “ ” is a point of covalent attachment to ring A.

[0995] In some embodiments, the compound comprises a portion having the formula,, , , ,,

[0996] wherein “ ” is a point of covalent attachment to ring A.

[0997] In some embodiments, the compound comprises a portion having the formula,

[0998] wherein “ ” is a point of covalent attachment to ring A.

[0999] In some embodiments, the compound comprises a portion having the formula,,

[1000] wherein “” is a point of covalent attachment to ring A.

[1001] In some embodiments, the compound comprises a portion having the formula,,,,, ,

[1002] wherein “ ” is a point of covalent attachment to ring A.

[1003] In some embodiments, the compound comprises a portion having the formula,

[1004] wherein “” is a point of covalent attachment to ring A.

[1005] In some embodiments, the compound comprises a portion having the formula,

[1006] wherein “ ” is a point of covalent attachment to ring A.

[1007] In some embodiments, the compound comprises a portion having the formula,,,,,

[01008] wherein “ ” is a point of covalent attachment to ring A.

[1009] In some embodiments, the compound comprises a portion having the formula,,,,,wherein “ ” is a point of covalent attachment to ring A.

[1010] In some embodiments, the compound comprises a portion having the formula,,,,,,,,,wherein “ ” is a point of covalent attachment to ring A

[1011] In some embodiments, the compound comprises a portion having the formula,,wherein “ ” is a point of covalent attachment to ring A.

[1012] In some embodiments, the compound comprises a portion having the formula,, ,,wherein “ ” is a point of covalent attachment to ring A.

[1013] In some embodiments, the compound comprises a portion (e.g., a ring B) havingthe formula,,

[1014] wherein

[1015] “” is a point of covalent attachment to ring A;

[1016] R1a is H orR1;

[1017] R1b is H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1- C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; and

[1018] R2a is H orR2.

[1019] In some embodiments, the compound comprises a portion (e.g., a ring B) havingthe formula,,,,,

[1020] wherein “” is a point of covalent attachment to ring A.

[1021] In some embodiments, the compound comprises a portion having the formula,,,,,

[1022] wherein “ ” is a point of covalent attachment to ring A.

[1023] In some embodiments, the compound comprises a portion of the formula, ,wherein “ ” is a point of covalent attachment to ring A. In some embodiments, each Rg isindependently hydroxy or optionally substituted C1-C6alkyl.

[1024] In some embodiments, the compound comprises a portion of the formula,wherein “ ” is a point of covalent attachment to ring A.

[1025] In some embodiments, ring B is a 5- to 10-membered heteroaryl, for example abicyclic heteroaryl (e.g., a 8-10 membered bicyclic heteroaryl), X is a bond, and an R1and an R2combine to form C3-C6cycloalkyl or 4- to 10-membered heterocycloalkyl. In some embodiments, the C3-C6cycloalkyl or 4- to 10-membered heterocycloalkyl can be optionally substituted, for example by one, two, three, or four Reand one, two, three, or four Rf, wherein an Reand an Rf, when present, may be taken together with the atom or atoms to which they are attached to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, each of which is optionally substituted by an one or more Rg.

[01026] In some embodiments, the compound comprises a portion of the formula, for examplewherein “ ” is a point of covalent attachment to ring A. In some embodiments, each Rgand Reis independently hydroxy or optionally substituted C1-C6alkyl.

[01027] In some embodiments, the compound comprises a portion of the formulawherein “ ” is a point of covalent attachment to ring A. In some embodiments, each Rg isindependently hydroxy or optionally substituted C1-C6alkyl.

[1028] In some embodiments, the compound comprises a portion of the formular wherein “ ” is a point of covalent attachment to ring A. In someembodiments, each Rgand Reis independently hydroxy or optionally substituted C1-C6alkyl.

[1029] In some embodiments, the compound comprises a portion of the formularwherein “ ” is a point of covalent attachment to ring A. In someembodiments, each Rgand Reis independently hydroxy or optionally substituted C1-C6alkyl.

[1030] In some embodiments, the compound comprises a portion of the formularwherein “ ” is a point of covalent attachment to ring A. In some embodiments, each Rgand Reis independently hydroxy or optionally substituted C1-C6alkyl.

[1031] In some embodiments, the compound comprises a portion of the formula,.

[1032] In some embodiments, the compound comprises a portion of the formulawherein “ ” is a point of covalent attachment to ring A.

[1033] In some embodiments, the compound comprises a portion of the formula,wherein “ ” is a point of covalent attachment to ring A.

[1034] In some embodiments, R6 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, or -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and -C1-C6alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[1035] In some embodiments, R6 is 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, or -C1-C6alkylene-(5- to 10-membered heteroaryl), wherein each hydrogen atom in 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and -C1-C6alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl),haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10- membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2. In some embodiments, R6is -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in -C1-C6alkylene-(4- to 10-membered heterocycloalkyl) is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[1036] In some embodiments, R6 is of the formula,,

[1037] wherein “ ” is a point of covalent attachment to X.

[1038] In some embodiments, R6 is of the formula,wherein “ ” is a point of covalent attachment to X.

[1039] In some embodiments, R6 is of the formula,,wherein “ ” is a point of covalent attachment to X.

[1040] In some embodiments, R6 is of the formula,, , , , , , , ,, , , , ,, , , , , ,, , , or ,

[1041] wherein “ ” is a point of covalent attachment to X.

[1042] In some embodiments, R6 is of the formula-CH3, , , , , , orwherein “ ” is a point of covalent attachment to X.

[1043] In some embodiments, R6 is of the formula,wherein “ ” is a point of covalent attachment to X.

[1044] In some embodiments, R6 is of the formula,,wherein “ ” is a point of covalent attachment to X.

[1045] In some embodiments, R6 is of the formula,,wherein “ ” is a point of covalent attachment to X.

[1046] In some embodiments, R6 is of the formula,wherein “ ” is a point of covalent attachment to X.

[1047] In some embodiments, R6 is of the formula,wherein “ ” is a point of covalent attachment to X.

[1048] In some embodiments, R6 is of the formula,wherein “ ” is a point of covalent attachment to X.

[1049] In some embodiments, R6 is of the formula,wherein “ ” is a point of covalent attachment to X.

[1050] In some embodiments, R6 is 4- to 10-membered heterocycloalkyl, wherein eachhydrogen atom in 4- to 10-membered heterocycloalkyl, is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10- membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

[1051] In some embodiments, R6 is of the formula,wherein “ ” is a point of covalent attachment to X.

[1052] In some embodiments, R6 is of the formulawherein “ ” is a point of covalent attachment to X.

[1053] In some embodiments, R6 is of the formulawherein “ ” is a point of covalent attachment to X.

[1054] In some embodiments, each Ra, Rb, Rc, Rd, Re, and Rf is independently selectedfrom the group consisting of H, deuterium, C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10- membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and C1-C6alkylene-(5- to 10- membered heteroaryl); or two of Raand Rb, or Rcand Rd, or Reand Rf, taken together with the atom or atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10- membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl; or Reand Rftaken together with the carbon atom to which they are attached form an oxo groups or a C2-C6alkenyl; wherein each hydrogen atom in C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10- membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and C1-C6alkylene-(5- to 10- membered heteroaryl) is independently optionally substituted by deuterium, halogen, or Rg.

[1055] In some embodiments, each Rg is independently optionally substituted C1-C6alkyl, optionally substituted C3-C6cycloalkyl, optionally substituted 4- to 10-membered heterocycloalkyl, optionally substituted C6-C10aryl, optionally substituted 5- to 10-memberedheteroaryl, -OH, -OC1-C6alkyl, -OC(O)C1-C6alkyl, -OC(O)N(H or C1-C6alkyl)2, -OS(O)C1-C6alkyl, -OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6alkyl)2, -OS(O)2N(H or C1-C6alkyl)2, -SC1-C6alkyl, -S(O)C1-C6alkyl, -S(O)2C1-C6alkyl, -S(O)N(H or C1-C6alkyl)2, -S(O)2N(H or C1-C6alkyl)2, -N(H or C1-C6alkyl)2, -N(C1-C6alkyl)C(O)-C1-C6alkyl, -N(C1-C6alkyl)C(O)OC1-C6alkyl, -N(C1-C6alkyl)C(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)C1-C6alkyl, -N(C1-C6alkyl)S(O)2C1-C6alkyl, -N(C1-C6alkyl)S(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)2N(H or C1-C6alkyl)2, -C(O)C1-C6alkyl, -C(O)OC1-C6alkyl, -C(O)N(H or C1-C6alkyl)2, -P(H or C1-C6alkyl)2, -P(O)(H or C1-C6alkyl)2, -P(O)2(H or C1-C6alkyl)2, -P(O)N(H or C1-C6alkyl)2, -P(O)2N(H or C1-C6alkyl)2, -P(O)OC1-C6alkyl, or-P(O)2OC1-C6alkyl.

[1056] In some embodiments, Ra’ is C1-C6 alkyl, for example methyl, ethyl, propyl,butyl, pentyl, or hexyl wherein each hydrogen atom in C1-C6alkyl is independently optionally substituted by deuterium, halogen, or Rg.

[1057] In some embodiments, Rb’ is C1-C6 alkylene-pyridyl (e.g., methylene-pyridyl,ethylene-pyridyl), wherein each hydrogen atom in C1-C6alkylene-pyridyl is independently optionally substituted by deuterium, halogen, or Rg.

[1058] In certain embodiments, if ring B is a 6-membered heteroaryl, then Y is -O-, -S-, -S(O)-, -S(O)2-, -NH-, -OCH2-, -CH2O-, -SCH2-, -CH2S-, -NHCH2-, or -CH2NH-; an R2and anR3, when present, taken together with the atoms to which they are attached, combine toform a C6-C8cycloalkyl or 6- to 8-membered heterocycloalkyl; or two R3, when present, taken together with the atom or atoms to which they are attached, combine to form a C4-C6cycloalkyl or 4- to 6-membered heterocycloalkyl; or combinations thereof.

[1059] In some embodiments, a compound is selected from Table 1 or 2. In someembodiments, a compound is selected from Table 1. In some embodiments, a compound is selected from Table 2.

[1060] The following in Table 1 represent illustrative embodiments of compounds ofFormula (I) Table 1

[1061] and pharmaceutically acceptable salts thereof.

[1062] The following in Table 2 represent illustrative embodiments of compounds ofFormula (I) Table 2

[1063] and pharmaceutically acceptable salts thereof.

[1064] In another aspect, the disclosure relates to a compound of the formulaan isotopically labeled form thereof, or a salt thereof, wherein R is H, methyl, isopropyl, or t-butyl. In some embodiments, R is H.

[1065] In another aspect, the disclosure relates to a method of comprisingcontactingn the presence of one or more solvents, thereby forming a salt of the formula, and isolating the salt. In some embodiments, the one or more solvents is ethanol, hepatane, or a mixture thereof.

[01066] In some embodiments, the method improves the chiral purity of the compondaccording to the formulaFor example, in some embodiments the method improves the chiral purity to greater than about 95%, greater than about 98%, or greater than about 99%. In some embodiment,s the method improvise the chiral purity by about 5%, about 8%, about 9%, or about 10% relative to the initial chiral purity.

[01067] In some embodiments, the step of isolating the salt is performed by filtrationthereby forming a filter cake. In some embodiments, the filter cake is washed with a solvent or mixture of solvents, for example ethanol and heptane.

[01068] In some embodiments, the salt is acidified, for example by HCl, to yield aat an increased chiral purity relative to the starting material from the step of contacting.

[01069] Those skilled in the art will recognize that the species listed or illustrated hereinare not exhaustive, and that additional species within the scope of these defined terms may also be selected. PHARMACEUTICAL COMPOSITIONS

[01070] For treatment purposes, pharmaceutical compositions comprising thecompounds described herein may further comprise one or more pharmaceutically-acceptable excipients. A pharmaceutically-acceptable excipient is a substance that is non-toxic and otherwise biologically suitable for administration to a subject. Such excipients facilitate administration of the compounds described herein and are compatible with the active ingredient. Examples of pharmaceutically-acceptable excipients include stabilizers, lubricants, surfactants, diluents, anti-oxidants, binders, coloring agents, bulking agents, emulsifiers, or taste-modifying agents. In preferred embodiments, pharmaceuticalcompositions according to the disclosure are sterile compositions. Pharmaceutical compositions may be prepared using compounding techniques known or that become available to those skilled in the art.

[1071] Sterile compositions are also contemplated by the disclosure, including compositions that are in accord with national and local regulations governing such compositions.

[1072] The pharmaceutical compositions and compounds described herein may be formulated as solutions, emulsions, suspensions, or dispersions in suitable pharmaceutical solvents or carriers, or as pills, tablets, lozenges, suppositories, sachets, dragees, granules, powders, powders for reconstitution, or capsules along with solid carriers according to conventional methods known in the art for preparation of various dosage forms. Pharmaceutical compositions of the disclosure may be administered by a suitable route of delivery, such as oral, parenteral, rectal, nasal, topical, or ocular routes, or by inhalation. Preferably, the compositions are formulated for intravenous or oral administration.

[1073] For oral administration, the compounds the disclosure may be provided in a solid form, such as a tablet or capsule, or as a solution, emulsion, or suspension. To prepare the oral compositions, the compounds of the disclosure may be formulated to yield a dosage of, e.g., from about 0.1 mg to 1 g daily, or about 1 mg to 50 mg daily, or about 50 to 250 mg daily, or about 250 mg to 1 g daily. Oral tablets may include the active ingredient(s) mixed with compatible pharmaceutically acceptable excipients such as diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservative agents. Suitable inert fillers include sodium and calcium carbonate, sodium and calcium phosphate, lactose, starch, sugar, glucose, methyl cellulose, magnesium stearate, mannitol, sorbitol, and the like. Exemplary liquid oral excipients include ethanol, glycerol, water, and the like. Starch, polyvinyl-pyrrolidone (PVP), sodium starch glycolate, microcrystalline cellulose, and alginic acid are exemplary disintegrating agents. Binding agents may include starch and gelatin. The lubricating agent, if present, may be magnesium stearate, stearic acid, or talc. If desired, the tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate to delay absorption in the gastrointestinal tract, or may be coated with an enteric coating.

[1074] Capsules for oral administration include hard and soft gelatin capsules. To prepare hard gelatin capsules, active ingredient(s) may be mixed with a solid, semi-solid, or liquid diluent. Soft gelatin capsules may be prepared by mixing the active ingredient with water, an oil, such as peanut oil or olive oil, liquid paraffin, a mixture of mono and di- glycerides of short chain fatty acids, polyethylene glycol 400, or propylene glycol.

[1075] Liquids for oral administration may be in the form of suspensions, solutions, emulsions, or syrups, or may be lyophilized or presented as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid compositions may optionally contain: pharmaceutically-acceptable excipients such as suspending agents (for example, sorbitol, methyl cellulose, sodium alginate, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel and the like); non-aqueous vehicles, e.g., oil (for example, almond oil or fractionated coconut oil), propylene glycol, ethyl alcohol, or water; preservatives (for example, methyl or propyl p-hydroxybenzoate or sorbic acid); wetting agents such as lecithin; and, if desired, flavoring or coloring agents.

[1076] For parenteral use, including intravenous, intramuscular, intraperitoneal, intranasal, or subcutaneous routes, the agents of the disclosure may be provided in sterile aqueous solutions or suspensions, buffered to an appropriate pH and isotonicity or in parenterally acceptable oil. Suitable aqueous vehicles include Ringer’s solution and isotonic sodium chloride. Such forms may be presented in unit-dose form such as ampoules or disposable injection devices, in multi-dose forms such as vials from which the appropriate dose may be withdrawn, or in a solid form or pre-concentrate that can be used to prepare an injectable formulation. Illustrative infusion doses range from about 1 to 1000 μg / kg / minute of agent admixed with a pharmaceutical carrier over a period ranging from several minutes to several days.

[1077] For nasal, inhaled, or oral administration, the inventive pharmaceutical compositions may be administered using, for example, a spray formulation also containing a suitable carrier. The inventive compositions may be formulated for rectal administration as a suppository.

[1078] For topical applications, the compounds of the present disclosure are preferably formulated as creams or ointments or a similar vehicle suitable for topical administration. For topical administration, the inventive compounds may be mixed with a pharmaceutical carrier at a concentration of about 0.1% to about 10% of drug to vehicle. Another mode of administering the agents of the disclosure may utilize a patch formulation to effect transdermal delivery.

[1079] As used herein, the terms “treat” or “treatment” encompass both “preventative” and “curative” treatment. “Preventative” treatment is meant to indicate a postponement of development of a disease, a symptom of a disease, or medical condition, suppressing symptoms that may appear, or reducing the risk of developing or re...

Claims

WHAT IS CLAIMED IS:

1. A compound of the formula I, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof,wherein ring A is 5- or 6-membered heteroaryl; ring B is a 5- to 10-membered heteroaryl or a 7- to 11-membered heterobicyclyl; X is a bond, -O-, -S-, or -NR7-; each of X1and X3is independently an -O-, -S-, -S(O)2-, or -CH2-, X2is a bond, -O-, -S-, -S(O)2-, or -CH2-, provided that no more than one of X1, X2, and X3is a -O-, -S-, or -S(O)2-; Y is -O-, -S-, -S(O)-, -S(O)2-, -NH-, -CH2-, -CH2CH2-, -OCH2-, -CH2O-, -SCH2-, -CH2S-, -S(O)CH2-, -CH2S(O)-, -S(O)2CH2-, -CH2S(O)2-, -NHCH2-, or -CH2NH-; each R1, when present, when bonded to carbon is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; each R1, when present, when bonded to nitrogen is independently deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), -C(O)Ra, -C(O)ORa, or -C(O)NRaRb; or two R1, when present, taken together with the atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-memberedheterocycloalkyl or a 5- to 10-membered heteroaryl; or an R1and an R2, when present, taken together with the atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, or a 5- to 10-membered heteroaryl; or an R1and R7, when present, taken together with the atoms to which they are attached, combine to form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, 5- to 10-membered heteroarylene-(5- to 10-membered heteroaryl), and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkyl-C(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each R2, when present, when bonded to carbon is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -ORa, -OC(O)Ra, -OC(O)NRaRb, -OC(=NRa)NRaRb, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRaRb, -OS(O)2NRaRb, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRaRb, -S(O)2NRaRb, -NRaRb, -NRaC(O)Rb, -NRaC(O)ORb, -NRaC(O)NRaRb, -NRaC(=NRa)NRaRb, -NRaS(O)Rb, -NRaS(O)2Rb, -NRaS(O)NRaRb, -NRaS(O)2NRaRb, -C(O)Ra, -C(O)ORa, -C(O)NRaRb, -C(=NRa)NRaRb, -PRaRb, -P(O)RaRb, -P(O)2RaRb, -P(O)NRaRb, -P(O)2NRaRb, -P(O)ORa, -P(O)2ORa, -CN, or -NO2; each R2, when present, when bonded to nitrogen is independently deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10- membered heteroaryl, -C(O)Ra, -C(O)ORa, or -C(O)NRaRb; or two R2, when present, taken together with the atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl; or an R2and an R3, when present, taken together with the atoms to which they are attached, combine to form a C6-C8cycloalkyl or 6- to 8-membered heterocycloalkyl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl, C6-C8cycloalkyl, and 6- to 8-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf,-NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each R3and R4, when present, is independently deuterium, halogen, C1-C6alkyl, C2- C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, -ORc, -OC(O)Rc, -OC(O)NRcRd, -OC(=NRc)NRcRd, -OS(O)Rc, -OS(O)2Rc, -OS(O)NRcRd, -OS(O)2NRcRd, -SRc, -S(O)Rc, -S(O)2Rc, -S(O)NRcRd, -S(O)2NRcRd, -NRcRd, -NRcC(O)Rd, -NRcC(O)ORd, -NRcC(O)NRcRd, -NRcC(=NRd)NRcRd, -NRcS(O)Rd, -NRcS(O)2Rd, -NRcS(O)NRcRd, -NRcS(O)2NRcRd, -C(O)Rc, -C(O)ORc, -C(O)NRcRd, -C(=NRc)NRcRd, -PRcRd, -P(O)RcRd, -P(O)2RcRd, -P(O)NRcRd, -P(O)2NRcRd, -P(O)ORc, -P(O)2ORc, -CN, or -NO2; or two R3or two R4, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6cycloalkyl or a 4- to 10-membered heterocycloalkyl; or two R3or two R4, when present, taken together with the carbon atom to which they are attached combine to form an oxo group or a C2-C6alkenyl group; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10- membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each R5, when present, is H, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl, wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, and 5- to 10-membered heteroaryl is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, C1-C6haloalkyl, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; R6is -C1-C6alkyl, -C2-C6alkenyl, -C2-C6alkynyl, -C3-C6cycloalkyl, 4- to 10- membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, or -C1-C6alkylene-(5- to10-membered heteroaryl), wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10- membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and -C1-C6alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), - OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6- C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; R7, when present, is H, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl; wherein each hydrogen atom in C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C10aryl, 5- to 10-membered heteroaryl, and 4- to 10-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-ORe, C1-C6alkyl-SRe, C1-C6alkyl-NReRf, C1-C6alkyl-C(O)Re, C1-C6alkylC(O)ORe, C1-C6alkyl-C(O)NReRf, -Re, -Rf, -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2; each Ra, Rb, Rc, Rd, Re, and Rfis independently selected from the group consisting of H, deuterium, C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and C1-C6alkylene-(5- to 10-membered heteroaryl); or two of Raand Rb, or Rcand Rd, or Reand Rf, taken together with the atom or atoms to which they are attached, combine to form a C3-C6cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-C10aryl, or 5- to 10-membered heteroaryl; or Reand Rftaken together with the carbon atom to which they are attached form an oxo groups or a C2-C6alkenyl; wherein each hydrogen atom in C1-C6alkyl, C1-C6alkyl-(O-C1-C6alkyl), C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6alkylene-(C3-C6cycloalkyl), 4- to 10-membered heterocycloalkyl, C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and C1-C6alkylene-(5- to 10-membered heteroaryl) is independently optionally substituted by deuterium, halogen, or Rg; each Rgis independently optionally substituted C1-C6alkyl, optionally substituted C3-C6cycloalkyl, optionally substituted 4- to 10-membered heterocycloalkyl, optionally substituted C6-C10aryl, optionally substituted 5- to 10-membered heteroaryl, -OH, -OC1-C6alkyl, -OC(O)C1-C6alkyl, -OC(O)N(H or C1-C6alkyl)2, -OS(O)C1-C6alkyl, -OS(O)2C1-C6alkyl, -OS(O)N(H or C1-C6alkyl)2, -OS(O)2N(H or C1-C6alkyl)2, -SC1-C6alkyl, -S(O)C1-C6alkyl, -S(O)2C1-C6alkyl, -S(O)N(H or C1-C6alkyl)2, -S(O)2N(H or C1-C6alkyl)2, -N(H or C1-C6alkyl)2, -N(C1-C6alkyl)C(O)-C1-C6alkyl, -N(C1-C6alkyl)C(O)OC1-C6alkyl, -N(C1-C6alkyl)C(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)C1-C6alkyl, -N(C1-C6alkyl)S(O)2C1-C6alkyl, -N(C1-C6alkyl)S(O)N(H or C1-C6alkyl)2, -N(C1-C6alkyl)S(O)2N(H or C1-C6alkyl)2, -C(O)C1-C6alkyl, -C(O)OC1-C6alkyl, -C(O)N(H or C1-C6alkyl)2, -P(H or C1-C6alkyl)2, -P(O)(H or C1-C6alkyl)2, -P(O)2(H or C1-C6alkyl)2, -P(O)N(H or C1-C6alkyl)2, -P(O)2N(H or C1-C6alkyl)2, -P(O)OC1-C6alkyl, or -P(O)2OC1-C6alkyl; m1 is 0, 1, or 2; m2 is 0, 1, or 2; m3 is 0 or 1; n1 is 0, 1, 2, 3, or 4; and n2 is 0, 1, 2, 3, or 4; provided that when ring B is a 6-membered heteroaryl, then: (i) Y is -O-, -S-, -S(O)-, -S(O)2-, -NH-, -OCH2-, -CH2O-, -SCH2-, -CH2S-, -NHCH2-, or -CH2NH-; or (ii) an R2and an R3, when present, taken together with the atoms to which they are attached, combine to form a C6-C8cycloalkyl or 6- to 8-membered heterocycloalkyl; or (iii) two R3, when present, taken together with the atom or atoms to which they are attached, combine to form a C4-C6cycloalkyl or 4- to 6-membered heterocycloalkyl; or (iv) combinations thereof.

2. The compound of claim 1, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula II.

3. The compound of claim 1, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula IIIwherein Y1 and Y2 are each independently N, O, S, CH, CR5, or C, provided that at least oneof Y1and Y2is N, O, or S and only one of Y1and Y2is O or S.

4. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula IVwherein Y1and Y2are each independently N, O, S, CH, or C, provided that at least one of Y1and Y2is N, O, or S and only one of Y1and Y2is O or S.

5. The compound of claim 1 or 3, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula Vwherein Y1and Y2are each independently N, O, S, CH, or C, provided that at least one of Y1and Y2is N, O, or S and only one of Y1and Y2is O or S, each of Z and Z1is independently N, CH, or CR1, and each of Z2and Z3is independently N, CH, or CR2.

6. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula VIwherein Y1and Y2are each independently N, O, S, CH, or C, provided that at least one of Y1and Y2is N, O, or S and only one of Y1and Y2is O or S, each of Z and Z1is independently N, CH, or CR1, and each of Z2and Z3is independently N, CH, or CR2.

7. The compound of claim 1, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula VII8. The compound of claim 1 or 2, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula VIII9. The compound of claim 1, 3, or 7, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula IX10. The compound of any one of claims 1 to 4, or 7 to 9, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula X11. The compound of any one of claims 1, 3, 5, 7, or 9, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula XI12. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula XII13. The compound of claim 1, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring B is a 5- to 10-membered heteroaryl.

14. The compound of claim 1 or 13, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring B is a 6-membered monocyclic heteroaryl.

15. The compound of claim 1 or 13, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring B is an 8- to 10-membered bicyclic heteroaryl.

16. The compound of claim 1, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring B is a 7- to 11-membered heterobicyclyl.

17. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein ring B is of the formula,wherein “ ” is a point of covalent attachment to ring A.

18. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formulawherein “ ” is a point of covalent attachment to ring A.

19. The compound of any one of claims 1, 13, 15, or 16, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula XIIIwherein each of Z, Z2, Z3, Z5, and Z6 is independently N, CH, CR1, or CR2, Z1 is N, C, CH,CR1, or CR2, and Z4 is C or N.

20. The compound of any one of claims 1, 13, 15, or 16, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula XIV21. The compound of any one of claims 1, 13, 15, or 16, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula XV22. The compound of any one of claims 1, 13, 15, or 16, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula XVI23. The compound of any one of claims 1, 13, 15, or 16, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula XVII24. The compound of any one of claims 1, 13, 15, or 16, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, having the formula XVIII25. The compound of any one of claims 1 to 13, 15 to 17, or 19 to 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula,26. The compound of any one of claims 1 to 13, 15 to 17, or 19 to 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula ,,,,,,,,,wherein “ ” is a point of covalent attachment to ring A.

27. The compound of any one of claims 1 to 13, 15 to 17, or 19 to 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula,,,,wherein “ ” is a point of covalent attachment to ring A.

28. The compound of any one of claims 1 to 13, 15 to 17, or 19 to 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula,,wherein “ ” is a point of covalent attachment to ring A.

29. The compound of any one of claims 1 to 13, 15 to 17, or 19 to 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula,wherein “ ” is a point of covalent attachment to ring A.

30. The compound of any one of claims 1 to 13, 15 to 17, or 19 to 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula ,, , , ,,wherein “ ” is a point of covalent attachment to ring A.

31. The compound of any one of claims 1 to 13, 15 to 17, or 19 to 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having theformula ,wherein “ ” is a point of covalent attachment to ring A.

32. The compound of any one of claims 1 to 13, 15 to 17, or 19 to 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula ,, , , , ,,wherein “ ” is a point of covalent attachment to ring A.

33. The compound of any one of claims 1 to 13, 15 to 17, or 19 to 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula,,, , , ,,,, ,wherein “ ” is a point of covalent attachment to ring A.

34. The compound of any one of claims 1 to 13, 15 to 17, or 19 to 24, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formula,wherein “ ” is a point of covalent attachment to ring A.

35. The compound of any one of claims 1 to 13 or 15 to 17, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, comprising a portion having the formulawherein “ ” is a point of covalent attachment to ring A.

36. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein X is -NR7-.

37. The compound of any one of claims 1 to 35, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein X is -O-.

38. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, or -C1-C6alkylene-(5- to 10-membered heteroaryl), wherein each hydrogen atom in 4- to 10-membered heterocycloalkyl, -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), 5- to 10-membered heteroaryl, and -C1-C6alkylene-(5- to 10-membered heteroaryl), is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, - C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

39. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R6is -C1-C6alkylene-(4- to 10-membered heterocycloalkyl), wherein each hydrogen atom in -C1-C6alkylene-(4- to 10-membered heterocycloalkyl) is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

40. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formula,,wherein “ ” is a point of covalent attachment to X.

41. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formula,wherein “ ” is a point of covalent attachment to X.

42. The compound of any one of claims 1 to 38, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formulawherein “ ” is a point of covalent attachment to X.

43. The compound of any one of claims 1 to 38, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is 4- to 10-membered heterocycloalkyl, wherein each hydrogen atom in 4- to 10-membered heterocycloalkyl, is independently optionally substituted by deuterium, halogen, -Re, -Rf, C1-C6alkyl, -C1-C6alkylene-(O-C1-C6alkyl), -OC1-C6alkylene-(O-C1-C6alkyl), -C1-C6alkylene-(O-Re), C6-C10aryl, -C1-C6alkylene-(C6-C10aryl), haloalkyl, C3-C6cycloalkyl, 5- to 10-membered heteroaryl, -C1-C6alkylene-(5- to 10-membered heterocycloalkyl), -ORe, -OC(O)Re, -OC(O)NReRf, -OS(O)Re, -OS(O)2Re, -OS(O)NReRf, -OS(O)2NReRf, -SRe, -S(O)Re, -S(O)2Re, -S(O)NReRf, -S(O)2NReRf, -NReRf, -NReC(O)Rf, -NReC(O)ORf, -NReC(O)NReRf, -NReC(=NRf)NReRf, -NReS(O)Rf, -NReS(O)2Rf, -NReS(O)NReRf, -NReS(O)2NReRf, -C(O)Re, -C(O)ORe, -C(O)NReRf, -PReRf, -P(O)ReRf, -P(O)2ReRf, -P(O)NReRf, -P(O)2NReRf, -P(O)ORe, -P(O)2ORe, -CN, or -NO2.

44. The compound of any one of claims 1 to 38 or 43, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein R6is of the formula ,wherein “ ” is a point of covalent attachment to X.

45. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein two R3, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a C3-C6cycloalkyl.

46. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein two R3, when present, taken together with the carbon atom or carbon atoms to which they are attached, combine to form a 4- to 6-membered heterocycloalkyl.

47. The compound of any one of claims 3 to 6 or 9 to 46, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y1, when present, is O.

48. The compound of any one of claims 3 to 6 or 9 to 47, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y2, when present, is N.

49. The compound of any one of claims 3 to 6 or 9 to 46, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y1, when present, is N.

50. The compound of any one of claims 3 to 6, 9 to 47, or 49, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein Y2, when present, is O.

51. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein n1 is 0 or 2.

52. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein n2 is 0.

53. The compound of any one of the preceding claims, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, wherein m3 is 0.

54. The compound of claim 1, selected from the group consisting of: 2-amino-3'-{8-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-7,8-dihydro-6H- pyrimido[5,4-b][1,4]oxazin-4-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{9-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethoxy]-9H-purin-6-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{9-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethoxy]-9H-purin-6-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile; 2-amino-3'-{8-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethoxy]-7,8-dihydro-6H-pyrimido[5,4- b][1,4]oxazin-4-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-[2-({1-[(dimethylamino)methyl]-2,2-difluorocyclopropyl}methoxy)-8-methyl- 7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{9-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-9H-purin-6-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile; 2-amino-3'-{9-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-9H-purin-6-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethoxy]pyrimidin-2-yl}-6,7-dihydro-5H- spiro[[1]benzothiophene-4,7'-[5]oxa[4]azatricyclo[6.1.1.02,6]deca[2(6),3]diene]-3- carbonitrile; 2-amino-3'-{6-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-2,6,7,8-tetrahydro-9-oxa- 1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-methyl-1H-pyrazole-3-carboxamide; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-b]pyridin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{6,7-dimethyl-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-2,6,7,8-tetrahydro-9-oxa- 1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{6-(2-hydroxyethyl)-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-2,6,7,8-tetrahydro-9- oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-methyl-7-[1-(1-methylpyrrolidin-2-yl)ethoxy]-1H-imidazo[4,5-b]pyridin-5- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; 2-amino-10'-[1-(1-methylpyrrolidin-2-yl)ethoxy]-5',5'a,6,6',7,7'-hexahydro-4'H,5H- spiro[[1]benzothiophene-4,3'-[2]oxa[1,9,11]triazadibenzo[cd,h]azulene]-3-carbonitrile; 6'-amino-3-{2-[1-(1-methylpyrrolidin-2-yl)ethoxy]pyrimidin-4-yl}-2',3',5,6-tetrahydro-4H- spiro[[1,2]benzoxazole-7,4'-thieno[2,3-b]pyran]-5'-carbonitrile; 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethoxy]-6,6a,7,8,9,10-hexahydropyrido[1,2- d]pyrimido[5,4-b][1,4]oxazin-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{7-(difluoromethyl)-8-ethyl-4-[1-(1-methylpyrrolidin-2-yl)ethoxy]-7,8-dihydro- 6H-pyrimido[5,4-b][1,4]oxazin-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{8-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,8-dihydro-6H-pyrimido[5,4- b][1,4]oxazin-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(2,2-difluoroethyl)-10-[1-(1-methylpyrrolidin-2-yl)ethyl]-5,6,9,10-tetrahydro- 4H,8H-pyrazino[3,2,1-de]pteridin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(4,7-diazaspiro[2.5]octan-7-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-(oxolan-3-yl)-1H-pyrazole-3-carboxamide; 2'-amino-6'-methyl-3-(1-(1-(1-methylpyrrolidin-2-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-6- yl)-5,5',6,6'-tetrahydro-4H-spiro[benzo[d]isoxazole-7,4'-cyclopenta[b]thiophene]-3'- carbonitrile; 2-amino-3'-{4-(6-methyl-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(6-methyl-7-oxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-[7-oxo-6-(oxolan-3-yl)-6,7-dihydro-2H- pyrazolo[3,4-c]pyridin-2-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-[7-oxo-6-(oxolan-3-yl)-4,5,6,7- tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-[7-oxo-6-(oxolan-3-yl)-4,5,6,7- tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-(3-methyloxetan-3-yl)-1H-pyrazole-3-carboxamide; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(1,4-oxazepan-4-yl)-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-chloro-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-methyl-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; 2-amino-3'-{3-fluoro-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; 2-amino-3'-{1-methyl-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-5- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; 2-amino-3'-{3-[1-(1-methylpyrrolidin-2-yl)ethyl]-1-(propan-2-yl)-1H-pyrazolo[4,3- d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-(2-hydroxyethyl)-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[4,3- d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{5-chloro-7-[1-(1-methylpyrrolidin-2-yl)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-2- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; 2-amino-3'-{9-[1-(1-methylpyrrolidin-2-yl)ethyl]-9H-purin-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-[1-(1-methylpyrrolidin-2-yl)ethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{7-(dimethylamino)-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-3H-[1,2,3]triazolo[4,5- d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{7-(methylamino)-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-3H-[1,2,3]triazolo[4,5- d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(6-aminopyridin-2-yl)ethyl]amino}-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;2-amino-3'-(4-{[1-(5-amino-1H-pyrazol-3-yl)ethyl]amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2,2-difluoroethyl)(methyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{7-(difluoromethyl)-6-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-2,6,7,8- tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxy-3-methylazepan-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(4-hydroxy-4-methylazepan-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(3-methyl-4,6,7,8- tetrahydropyrazolo[4,3-c]azepin-5(1H)-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[(1-methylpyrrolidin-2-yl)methyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{2-[1-(1-methylpyrrolidin-2-yl)ethoxy]pyrimidin-4-yl}-6,6',7,7'-tetrahydro- 5H,5'H-spiro[[1]benzothiophene-4,8'-imidazo[1,5-a]pyridine]-3-carbonitrile; 2-amino-3'-{1-[2-(dimethylamino)cyclobutyl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-[1-(1,2-dimethylpiperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-(4-{[2-(methanesulfonyl)ethyl](methyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxy-3-methylpyrrolidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3,3-difluoropiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(2-oxa-6-azaspiro[3.5]nonan-6-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxyazetidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxy-3-methylazetidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(methylamino)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(dimethylamino)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{7-hydroxy-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-3H-[1,2,3]triazolo[4,5- d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 1-{2-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-8-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,8-dihydro-6H-pyrimido[5,4- b][1,4]oxazin-4-yl}-N-methyl-1H-pyrazole-3-carboxamide; 1-{6-(2-amino-3-cyano-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4- d][1,2]oxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-methyl-1H-pyrazole-3-carboxamide; 2-amino-3'-{4-(3-hydroxy-2,2-dimethylazetidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{7-(3-hydroxy-3-methylpiperidin-1-yl)-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-3H- [1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(1-oxa-6-azaspiro[3.5]nonan-6-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-hydroxypropyl)amino]-3-(1-methyl-1H-pyrazol-3-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)amino]-3-(1-methyl-1H-pyrazol-3-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{9-hydroxy-9-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethoxy]-6,6a,7,8,9,10- hexahydropyrido[1,2-d]pyrimido[5,4-b][1,4]oxazin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[1-{1-[(2S)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-(3-hydroxy-3- methylpiperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-[1-{1-[(2R)-3-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-(3-hydroxy-3- methylpiperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2,2-difluorocyclopropyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(cyclopropylamino)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[(1-hydroxycyclobutyl)methyl](methyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-hydroxyethyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-hydroxyethyl)(methyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[(1-hydroxycyclopropyl)methyl]amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(2-hydroxy-2-methylpropoxy)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{4-[(2-hydroxycyclopropyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(dimethylamino)propan-2-yl]-4-(3-hydroxy-3-methylpiperidin-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-cyano-3-hydroxypiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3,4-dihydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-cyanopiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(5-oxo-1,4-diazepan-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(3-oxo-1,4-diazepan-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(4-cyanoazepan-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[5-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-6-[1-(1-methylpyrrolidin-2- yl)ethoxy]pyrimidin-2-yl}-4',5',6,6',7,7'-hexahydro-5H-spiro[[1]benzothiophene-4,8'- cyclohepta[d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethoxy]pyrimidin-2-yl}-4',5',6,6',7,7'-hexahydro- 5H-spiro[[1]benzothiophene-4,8'-cyclohepta[d][1,2]oxazole]-3-carbonitrile;2-amino-3'-{4-[(2-hydroxycyclopropyl)amino]-3-methoxy-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-cyano-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; 2-amino-3'-{3-cyano-4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-cyano-4-[(2-hydroxy-2-methylpropyl)amino]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[ethyl(2-hydroxy-2-methylpropyl)amino]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2,2-difluoroethyl)(2-hydroxy-2-methylpropyl)amino]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[(1-hydroxycyclopropyl)methyl](methyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-(1-methylazetidin-3-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-(1-methylpyrrolidin-3-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-(4-fluoro-1-methylpyrrolidin-3-yl)-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(3-fluoro-1-methylpyrrolidin-2-yl)ethyl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-[1-(3-methoxy-1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-[1-(1-methylpyrrolidin-2- yl)ethyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-[1-(1-methylpyrrolidin-2- yl)ethyl]-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(1-hydroxycyclopropyl)methoxy]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{7-[(2-hydroxy-2-methylpropyl)(methyl)amino]-3-[1-(1-methylpyrrolidin-2- yl)ethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[4-(dimethylamino)oxolan-3-yl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[(1-cyanocyclopropyl)methyl]amino}-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;2-amino-3'-[8-(1,2-dimethylpiperidin-3-yl)-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-2- yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}piperidine-3-carboxamide; 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-tert-butyl-3-hydroxypiperidine-3-carboxamide; 2-amino-3'-[3-(1-methyl-1H-pyrazol-3-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4- (methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-hydroxy-3-(1-methyl-1H-pyrazol-3-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 5-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N,N-dimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxamide; 2-amino-3'-{4-[3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(2,2-dioxo-2λ6-thia-1,3,7-triazaspiro[4.5]decan-7-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(2-cyanomorpholin-4-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;2-amino-3'-(4-{[(3-hydroxyoxetan-3-yl)methyl](methyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(2,5-dioxa-8-azaspiro[3.5]nonan-8-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[3-(methanesulfonyl)pyrrolidin-1-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2,2-difluoroethyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxypiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[3-hydroxy-3-(trifluoromethyl)piperidin-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-3-hydroxypiperidine-3-carboxamide; 2-amino-3'-{1-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-4-(methylsulfanyl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-cyano-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-cyanopropyl)(methyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile;2-amino-3'-[1-{1-[1-(2-hydroxyethyl)pyrrolidin-2-yl]ethyl}-4-(3-hydroxy-3-methylpiperidin- 1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[3-(methanesulfonyl)piperidin-1-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxy-3,5-dimethylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-cyclopropylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3-methylpiperidin-1- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-cyano-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(methylsulfanyl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; methyl 6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidine- 3-carboxylate; 2-amino-3'-{4-[3-(2-hydroxypropan-2-yl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(ethylamino)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-[3-chloro-1-(1,2-dimethylpiperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-methyl-1H-pyrazol-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-methyl-1H-pyrazole-4-carboxamide;2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(piperidin-1-yl)-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[3-(hydroxymethyl)-4-methyl-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(methylsulfanyl)-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[4-fluoro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(4-chloro-3-methyl-1H-pyrazol-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 3'-{4-(3-acetyl-1H-pyrazol-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-2-amino-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-cyano-4-hydroxypiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[4-chloro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[3-(difluoromethyl)-3-hydroxypiperidin-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[3-(1-hydroxyethyl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{4-[3-(hydroxymethyl)azetidin-1-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[3-(hydroxymethyl)pyrrolidin-1-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[4-(hydroxymethyl)-2H-1,2,3-triazol-2-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3,5-dihydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(5-hydroxy-2,5-dimethylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-cyano-1H-pyrazol-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[8-(methoxyimino)-3-azabicyclo[3.2.1]octan-3-yl]-1-[1-(1-methylpyrrolidin- 2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-methyl-2H-1,2,3-triazole-4-carboxamide; 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N-methyl-1H-1,2,3-triazole-4-carboxamide;2-amino-3'-{4-(4-cyano-1H-pyrazol-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[4-(methoxyimino)piperidin-1-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(pyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-(1-methyl-1H-pyrazol-3-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-ethylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3-methylpiperidin-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidine- 3-carboxamide; 2-amino-3'-{4-(4-aminopiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(8-amino-3-azabicyclo[3.2.1]octan-3-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxy-5-methoxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(6-hydroxy-5,6-dihydrocyclopenta[c]pyrazol-2(4H)-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'- pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{4-[3-(hydroxymethyl)-1H-pyrrol-1-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-cyano-4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-[1-(2-hydroxyethyl)-1H-pyrazol-3-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[6-(hydroxymethyl)pyridin-2-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[5-fluoro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{6-(3-hydroxy-3-methylpiperidin-1-yl)-9-[1-(1-methylpyrrolidin-2-yl)ethyl]-9H- purin-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; 2-amino-3'-{4-(7-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-[4-(3-hydroxy-3-methylpiperidin-1-yl)-1-{1-[1-(2H3)methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{1-[1-(1-ethylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3-methylpiperidin-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'- pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; 1-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-1H-pyrazole-3-sulfonamide; 2-amino-3'-{1-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3-methylpiperidin- 1-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene- 4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-7-[1-(1-methylpyrrolidin-2-yl)ethyl]-7H- pyrrolo[2,3-d]pyrimidin-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[(2-cyano-2-methylpropyl)(methyl)amino]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(5-fluoro-3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-6,7-dihydro- 4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{4-(3,5-dihydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{4-(3-cyano-4-hydroxypiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-ethylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3-methylpiperidin-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazole]-3-carbonitrile;2-amino-3'-{4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(pyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-4,6,7,7a,8,9,10,11- octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-chloro-4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-cyano-4-(2-hydroxy-2-methylpropoxy)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-cyano-4-[3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-cyano-1-[1-(1-ethylpyrrolidin-2-yl)ethyl]-4-(3-hydroxy-3-methylpiperidin-1- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-cyano-4-(3-hydroxy-3-methylpiperidin-1-yl)-1-[1-(pyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[2-(hydroxymethyl)-1H-pyrrol-1-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-4,6,7,7a,8,9,10,11- octahydro-1,3,4,5,6,11a-hexaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile;2-amino-3'-{10-hydroxy-10-methyl-4-[1-(pyrrolidin-2-yl)ethyl]-7,7a,8,9,10,11-hexahydro- 4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(1-ethylpyrrolidin-2-yl)ethyl]-10-hydroxy-10-methyl-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(3-fluoro-1-methylpyrrolidin-2-yl)ethyl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-4-[1-(3-methoxy-1-methylpyrrolidin-2-yl)ethyl]-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa- 1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7a,8,9,10,11,12-hexahydro-4H,7H-6-oxa- 1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,7a,8,9,11,12-hexahydro-4H-6,10-dioxa- 1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7a,8,11,12-tetrahydro-4H,7H,10H-6,9- dioxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-4,7a,8,9,10,11- hexahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,7a,8,9,10,11- hexahydro-4H-6-thia-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{7-(3-hydroxy-3-methylpiperidin-1-yl)-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-3H- [1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'- pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{3-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-7-(3-hydroxy-3-methylpiperidin- 1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-7-(3-hydroxy-3-methylpiperidin- 1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{7-(3-hydroxy-3-methylpiperidin-1-yl)-3-[1-(1-methylpyrrolidin-2-yl)ethyl]-3H- [1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{3-[1-(4-fluoro-1-methylpyrrolidin-2-yl)ethyl]-7-(3-hydroxy-3-methylpiperidin- 1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylazetidin-2-yl)ethyl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1,4,4-trimethylazetidin-2-yl)ethyl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(dimethylamino)propan-2-yl]-10-hydroxy-10-methyl-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-6,6-dioxo- 4,6,7,7a,8,9,10,11-octahydro-6λ6-thia-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-[10-hydroxy-10-methyl-4-(1-methyloctahydro-1H-indol-7-yl)-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[10-hydroxy-10-methyl-4-(1-methyloctahydropyrano[4,3-b]pyrrol-7-yl)- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 3'-{4-hydroxy-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-2- {[(1H-pyrrol-2-yl)methyl]amino}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{9-hydroxy-9-methyl-6-methylidene-4-[1-(1-methylpyrrolidin-2-yl)ethyl]- 6,6a,7,8,9,10-hexahydro-4H-1,3,4,5,10a-pentaazaacephenanthrylen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-cyano-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(piperidin-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-[4-(3-hydroxy-3-methylpiperidin-1-yl)-1-(1-methyloctahydro-1H-indol-7-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-(2-hydroxy-2-methylpropyl)-4-[1-(1-methylpyrrolidin-2-yl)ethoxy]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(hexahydro-1H-pyrrolizin-3-yl)ethyl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[3-(pyrrolidin-1-yl)butan-2-yl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{10-hydroxy-10-methyl-4-[1-(pyrrolidin-1-yl)propan-2-yl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[3-(azetidin-1-yl)butan-2-yl]-10-hydroxy-10-methyl-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7-oxo- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a-hexaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-6,10-dimethyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7-oxo- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a-hexaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(pyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-[1-(3-hydroxycyclobutyl)-1H-pyrazol-3-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-methyl-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-[4-(7-amino-6-methyl-1,3,4,6-tetrahydro-5H-pyrido[3,4-f][1,4]oxazocin-5-yl)-1- methyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-[1-(2-hydroxypropyl)-1H-pyrazol-3-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,7a,8,9,10,11-hexahydro-4H- 6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl]amino}-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(2-aminopyridin-3-yl)ethoxy]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{3-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-3-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[2-(dimethylamino)cyclopentyl]-10-hydroxy-10-methyl-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(4-methyl-2,4,6,7-tetrahydro-5H- pyrazolo[4,3-f][1,4]oxazepin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[2-(azetidin-1-yl)cyclopentyl]-10-hydroxy-10-methyl-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[2-(2-aminopyridin-3-yl)pyrrolidin-1-yl]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{6-[(2-aminopyridin-3-yl)methyl]-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-2,6,7,8- tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{7-(2-aminopyridin-3-yl)-6-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-2,6,7,8- tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(3-aminopyrazin-2-yl)ethyl](ethyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{6-[1-(5-methyl-1H-pyrazol-4-yl)ethyl]-2-[1-(1-methylpyrrolidin-2-yl)ethyl]- 2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(4-methyl-2,6,7,9- tetrahydropyrazolo[4,3-f][1,4]oxazocin-5(4H)-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(4-methyl-2,4,7,8- tetrahydropyrazolo[3,4-b][1,5]oxazocin-5(6H)-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{6-[1-(2-aminopyridin-3-yl)ethyl]-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-2,6,7,8- tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(6-amino-5-methyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin-4(5H)-yl)-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(4-fluoro-1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](2-cyanoethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(7-amino-6-methyl-1,3,4,6-tetrahydro-5H-pyrido[3,4-f][1,4]oxazocin-5-yl)-1- [1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](2,2-difluoroethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-[4-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-7-methyl-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,8-dihydro-9-oxa- 1,2,3,5,6-pentaazabenzo[cd]azulen-6(2H)-yl]-1,4-anhydro-2,3,5-trideoxypentitol; 2-[4-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-2-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,8-dihydro-9-oxa-1,2,3,5,6- pentaazabenzo[cd]azulen-6(2H)-yl]-1,4-anhydro-2,3,5-trideoxypentitol; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(tetrahydro-1H-pyrrolizin-7a(5H)-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{9-hydroxy-6,9-dimethyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-6,6a,7,8,9,10- hexahydro-4H-1,3,4,5,10a-pentaazaacephenanthrylen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{2-(2-hydroxy-2-methylpropyl)-6-[1-(1-methylpyrrolidin-2-yl)ethyl]-2,6,7,8- tetrahydro-1,2,3,5,6-pentaazaacenaphthylen-4-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-[2-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-9-[1-(1-methylpyrrolidin-2-yl)ethyl]-5-oxo-8,9-dihydro-7H- imidazo[4,5,1-de]pteridin-4(5H)-yl]-1,4-anhydro-2,3,5-trideoxypentitol; 2-amino-3'-{9-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(3-oxabicyclo[3.1.0]hexan-1-yl)-5-oxo- 4,5,8,9-tetrahydro-7H-imidazo[4,5,1-de]pteridin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(2-hydroxy-2-methylpropyl)-9-[1-(1-methylpyrrolidin-2-yl)ethyl]-5-oxo- 4,5,8,9-tetrahydro-7H-imidazo[4,5,1-de]pteridin-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{9-[1-(1-methylpyrrolidin-2-yl)ethyl]-5-oxo-4-(oxolan-3-yl)-4,5,8,9-tetrahydro- 7H-imidazo[4,5,1-de]pteridin-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-4,6,7,7a,8,9,10,11- octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(tetrahydro-1H-pyrrolizin-7a(5H)-yl)ethyl]- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(1-ethylpyrrolidin-2-yl)ethyl]-10-hydroxy-10-methyl-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(3-oxo-2,8-diazaspiro[4.5]decan-8-yl)- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(2-ethyl-5-hydroxy-5-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl](6,6,7,7-2H4)- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{9-hydroxy-6,9-dimethyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,8,9,10- tetrahydro-4H-1,3,4,5,10a-pentaazaacephenanthrylen-2-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[3-(1-hydroxyethyl)pyridin-2-yl]amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylazetidin-2-yl)ethyl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-[10-hydroxy-10-(2H3)methyl-4-{1-[1-(2H3)methylpyrrolidin-2-yl]ethyl}- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-6-oxo- 4,6,7,7a,8,9,10,11-octahydro-6λ4-thia-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-(4-cyano-2-methylpiperidin-1-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-7,10-dimethyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](methyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{ethyl[1-(6-hydroxypyridin-3-yl)ethyl]amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{1-[1-(1-methylpyrrolidin-2-yl)ethyl]-4-(6-oxa-1-azaspiro[3.5]nonan-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{8-hydroxy-8-methyl-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1,3,5,5a,6,7,8,9- octahydro-4-oxa-1,2,9a,10,12-pentaazabenzo[4,5]cycloocta[1,2,3-cd]inden-11-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 3'-{4-[(1-acetylpyrrolidin-3-yl)(ethyl)amino]-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H- pyrazolo[3,4-d]pyrimidin-6-yl}-2-amino-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 5-{6-(2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl)-1-[1-(1-methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-4- yl}-N,N,3-trimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2-carboxamide; 2-amino-3'-{4-[2-(hydroxymethyl)-2-methylazetidin-1-yl]-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-4,6,7,7a,8,9,10,11- octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; 2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl](7,7-2H2)- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-[(7aS)-10-hydroxy-10-methyl-4-{1-[1-(2H3)methylpyrrolidin-2-yl]ethyl}- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl]amino}-1-[1-(1-methylpyrrolidin-2-yl)ethyl]- 1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(2-aminopyridin-3-yl)ethyl](methyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile; 2-amino-3'-{6-ethyl-10-hydroxy-10-methyl-4-[1-(1-methylpyrrolidin-2-yl)ethyl]-7-oxo- 4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a-hexaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[(3,5-dimethyl-1H-pyrazol-4-yl)methyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-{4-[1-(1,5-dimethylpyrrolidin-2-yl)ethyl]-10-hydroxy-10-methyl-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[(2-aminopyridin-3-yl)methyl](ethyl)amino}-1-[1-(1-methylpyrrolidin-2- yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-amino-3'-{10-hydroxy-10-methyl-4-[1-(1,5,5-trimethylpyrrolidin-2-yl)ethyl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-amino-3'-(4-{[1-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; and 2-amino-3'-(4-{[1-(2-amino-6-methylpyridin-3-yl)ethyl](ethyl)amino}-1-[1-(1- methylpyrrolidin-2-yl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

55. The compound of claim 1, selected from the group consisting of: (4S)-2-amino-3'-{8-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-7,8-dihydro- 6H-pyrimido[5,4-b][1,4]oxazin-4-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(9-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-9H-purin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(8-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-7,8-dihydro- 6H-pyrimido[5,4-b][1,4]oxazin-4-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[2-({(1S)-1-[(dimethylamino)methyl]-2,2-difluorocyclopropyl}methoxy)-8- methyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[2-({(1R)-1-[(dimethylamino)methyl]-2,2-difluorocyclopropyl}methoxy)-8- methyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{9-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-9H-purin-6- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3- carbonitrile;(4S)-2-amino-3'-{9-methyl-2-[(tetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy]-9H-purin-6- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4R)-2-amino-3'-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-6,7- dihydro-5H-spiro[[1]benzothiophene-4,7'- [5]oxa[4]azatricyclo[6.1.1.02,6]deca[2(6),3]diene]-3-carbonitrile; (4S)-2-amino-3'-(6-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-2,6,7,8- tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-methyl-1H-pyrazole-3-carboxamide; 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1R)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-methyl-1H-pyrazole-3-carboxamide; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-b]pyridin- 6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4S)-2-amino-3'-[(7R)-6,7-dimethyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-2,6,7,8- tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[6-(2-hydroxyethyl)-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-2,6,7,8- tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-methyl-7-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-1H- imidazo[4,5-b]pyridin-5-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (3'R,5'aS)-2-amino-10'-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-5',5'a,6,6',7,7'- hexahydro-4'H,5H-spiro[[1]benzothiophene-4,3'-[2]oxa[1,9,11]triazadibenzo[cd,h]azulene]- 3-carbonitrile; (4'S)-6'-amino-3-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-2',3',5,6- tetrahydro-4H-spiro[[1,2]benzoxazole-7,4'-thieno[2,3-b]pyran]-5'-carbonitrile; (4S)-2-amino-3'-[(6aR)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}-6,6a,7,8,9,10- hexahydropyrido[1,2-d]pyrimido[5,4-b][1,4]oxazin-2-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7S)-7-(difluoromethyl)-8-ethyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-2-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(8-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,8-dihydro-6H- pyrimido[5,4-b][1,4]oxazin-2-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(2,2-difluoroethyl)-10-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 5,6,9,10-tetrahydro-4H,8H-pyrazino[3,2,1-de]pteridin-2-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(4,7-diazaspiro[2.5]octan-7-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-[(3R)-oxolan-3-yl]-1H-pyrazole-3-carboxamide; 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-[(3S)-oxolan-3-yl]-1H-pyrazole-3-carboxamide; and (6'S,7S)-2'-amino-6'-methyl-3-(1-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethyl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl)-5,5',6,6'-tetrahydro-4H-spiro[benzo[d]isoxazole-7,4'- cyclopenta[b]thiophene]-3'-carbonitrile; (4S)-2-amino-3'-[4-(6-methyl-7-oxo-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl)-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(6-methyl-7-oxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl)-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3S)-oxolan-3- yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3R)-oxolan-3- yl]-6,7-dihydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3S)-oxolan-3- yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-{7-oxo-6-[(3R)-oxolan-3- yl]-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridin-2-yl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(2-oxa-5,8- diazaspiro[3.5]nonan-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(2,2-difluoro-5,8-diazaspiro[3.5]nonan-8-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-(3-methyloxetan-3-yl)-1H-pyrazole-3-carboxamide; (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(1,4-oxazepan-4-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-chloro-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-methyl-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-fluoro-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-methyl-3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[4,3- d]pyrimidin-5-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1-(propan-2-yl)-1H- pyrazolo[4,3-d]pyrimidin-5-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[1-(2-hydroxyethyl)-3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[4,3-d]pyrimidin-5-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(5-chloro-7-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7H-pyrrolo[2,3- d]pyrimidin-2-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(9-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-9H-purin-2-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-3H-[1,2,3]triazolo[4,5- d]pyrimidin-5-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[7-(dimethylamino)-3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-3H- [1,2,3]triazolo[4,5-d]pyrimidin-5-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[7-(methylamino)-3-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-3H- [1,2,3]triazolo[4,5-d]pyrimidin-5-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(6-aminopyridin-2-yl)ethyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(5-amino-1H-pyrazol-3-yl)ethyl]amino}-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2,2-difluoroethyl)(methyl)amino]-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7S)-7-(difluoromethyl)-6-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylazepan-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S)-3-hydroxy-3-methylazepan-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(4R)-4-hydroxy-4-methylazepan-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(4S)-4-hydroxy-4-methylazepan-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(3-methyl-4,6,7,8- tetrahydropyrazolo[4,3-c]azepin-5(1H)-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{[(2S)-1-methylpyrrolidin-2- yl]methyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)amino]-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4R)-2-amino-3'-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-6,6',7,7'- tetrahydro-5H,5'H-spiro[[1]benzothiophene-4,8'-imidazo[1,5-a]pyridine]-3-carbonitrile; (4S)-2-amino-3'-(2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-4-yl)-6,6',7,7'-tetrahydro-5H,5'H-spiro[[1]benzothiophene-4,8'-imidazo[1,5-a]pyridine]-3-carbonitrile; (4S)-2-amino-3'-{1-[(1S,2S)-2-(dimethylamino)cyclobutyl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{1-[(2R,3R)-1,2-dimethylpiperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-6- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4S)-2-amino-3'-(4-{[2-(methanesulfonyl)ethyl](methyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(3,3-difluoropiperidin-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(2-oxa-6- azaspiro[3.5]nonan-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(3-hydroxyazetidin-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(3-hydroxy-3-methylazetidin-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(methylamino)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(dimethylamino)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(7-hydroxy-3-{1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-3H- [1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; 1-(2-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-8-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,8-dihydro-6H- pyrimido[5,4-b][1,4]oxazin-4-yl)-N-methyl-1H-pyrazole-3-carboxamide; 1-(6-[(4S)-2-amino-3-cyano-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'- pyrano[3,4-d][1,2]oxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-4-yl)-N-methyl-1H-pyrazole-3-carboxamide; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-2,2-dimethylazetidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(7-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-3-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4S)-1-oxa-6- azaspiro[3.5]nonan-6-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(2S)-2-hydroxypropyl]amino}-3-(1-methyl-1H-pyrazol-3-yl)-1-{(1S)- 1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;(4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)amino]-3-(1-methyl-1H-pyrazol-3-yl)-1- {(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(6aR,9R)-9-hydroxy-9-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}-6,6a,7,8,9,10-hexahydropyrido[1,2-d]pyrimido[5,4-b][1,4]oxazin-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(3R)-3- hydroxy-3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{1-[(2R,3S)-3-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(3R)-3-hydroxy- 3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2R,3S)-3-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(3R)-3- hydroxy-3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2,2-difluorocyclopropyl)amino]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(cyclopropylamino)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1-hydroxycyclobutyl)methyl](methyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-hydroxyethyl)amino]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-hydroxyethyl)(methyl)amino]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1-hydroxycyclopropyl)methyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(2-hydroxy-2-methylpropoxy)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-hydroxycyclopropyl)amino]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1S,2S)-2-hydroxycyclopropyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R,2R)-2-hydroxycyclopropyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{1-[(2S)-1-(dimethylamino)propan-2-yl]-4-[(3R)-3-hydroxy-3- methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-cyano-3-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S,4S)-3,4-dihydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S,4R)-3,4-dihydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R,4R)-3,4-dihydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-cyanopiperidin-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S)-3-cyanopiperidin-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(5-oxo-1,4-diazepan-1- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(3-oxo-1,4-diazepan-1- yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(4S)-4-cyanoazepan-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(4R)-4-cyanoazepan-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[5-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-4',5',6,6',7,7'-hexahydro-5H- spiro[[1]benzothiophene-4,8'-cyclohepta[d][1,2]oxazole]-3-carbonitrile; (4R)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-6-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)-4',5',6,6',7,7'-hexahydro-5H- spiro[[1]benzothiophene-4,8'-cyclohepta[d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy}pyrimidin-2-yl)- 4',5',6,6',7,7'-hexahydro-5H-spiro[[1]benzothiophene-4,8'-cyclohepta[d][1,2]oxazole]-3- carbonitrile; (4S)-2-amino-3'-(4-{[(1S,2S)-2-hydroxycyclopropyl]amino}-3-methoxy-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R,2R)-2-hydroxycyclopropyl]amino}-3-methoxy-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;(4S)-2-amino-3'-(3-cyano-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-cyano-4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-cyano-4-[(2-hydroxy-2-methylpropyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[ethyl(2-hydroxy-2-methylpropyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2,2-difluoroethyl)(2-hydroxy-2-methylpropyl)amino]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1-hydroxycyclopropyl)methyl](methyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-(1-methylazetidin-3-yl)- 1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene- 4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-[(3S)-1-methylpyrrolidin- 3-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{1-[(3R,4S)-4-fluoro-1-methylpyrrolidin-3-yl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{1-[(3R,4R)-4-fluoro-1-methylpyrrolidin-3-yl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2R,3S)-3-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(2-hydroxy- 2-methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2R,3S)-3- methoxy-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(2-hydroxy- 2-methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-{1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-7-{(1R)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(1-hydroxycyclopropyl)methoxy]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(7-[(2-hydroxy-2-methylpropyl)(methyl)amino]-3-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(7-[(2-hydroxy-2-methylpropyl)(methyl)amino]-3-{(1R)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{1-[4-(dimethylamino)oxolan-3-yl]-4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{1-[(3R,4R)-4-(dimethylamino)oxolan-3-yl]-4-[(2-hydroxy-2- methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1-cyanocyclopropyl)methyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{8-[(2R,3R)-1,2-dimethylpiperidin-3-yl]-7,8-dihydro-6H-pyrimido[5,4- b][1,4]oxazin-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (3S)-1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)piperidine-3-carboxamide; 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-tert-butyl-3-hydroxypiperidine-3-carboxamide; (4S)-2-amino-3'-[3-(1-methyl-1H-pyrazol-3-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-4-(methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-hydroxy-3-(1-methyl-1H-pyrazol-3-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 5-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N,N-dimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2- carboxamide; (4S)-2-amino-3'-(4-[3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(5R)-2,2-dioxo-2λ6-thia-1,3,7-triazaspiro[4.5]decan-7-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(5S)-2,2-dioxo-2λ6-thia-1,3,7-triazaspiro[4.5]decan-7-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(4-oxa-7- azaspiro[2.5]octan-7-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2S)-2-cyanomorpholin-4-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(3-hydroxyoxetan-3-yl)methyl](methyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(2,5-dioxa-8-azaspiro[3.5]nonan-8-yl)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-(methanesulfonyl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S)-3-(methanesulfonyl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2,2-difluoroethyl)amino]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-(trifluoromethyl)piperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S)-3-hydroxy-3-(trifluoromethyl)piperidin-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (3R)-1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-3-hydroxypiperidine-3-carboxamide; (3S)-1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-3-hydroxypiperidine-3-carboxamide; (4S)-2-amino-3'-[1-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4- (methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S)-3-cyano-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-cyano-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-cyanopropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-(2-hydroxyethyl)pyrrolidin-2-yl]ethyl}-4-[(3R)-3- hydroxy-3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S)-3-(methanesulfonyl)piperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-(methanesulfonyl)piperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R,5R)-3-hydroxy-3,5-dimethylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;(4S)-2-amino-3'-(4-[(3S,5R)-3-hydroxy-3,5-dimethylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-cyclopropylpyrrolidin-2-yl]ethyl}-4-[(3R)-3-hydroxy-3- methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[3-cyano-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4- (methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; methyl 6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidine-3-carboxylate; (4S)-2-amino-3'-(4-[3-(2-hydroxypropan-2-yl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(ethylamino)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{3-chloro-1-[(2R,3R)-1,2-dimethylpiperidin-3-yl]-1H-pyrazolo[3,4- d]pyrimidin-6-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(3-methyl-1H-pyrazol-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-methyl-1H-pyrazole-4-carboxamide; (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(piperidin-1-yl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[3-(hydroxymethyl)-4-methyl-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(methylsulfanyl)-1H- pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[4-fluoro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(4-chloro-3-methyl-1H-pyrazol-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-3'-[4-(3-acetyl-1H-pyrazol-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H- pyrazolo[3,4-d]pyrimidin-6-yl]-2-amino-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R,4S)-3-cyano-4-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S,4R)-3-cyano-4-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S,4S)-3-cyano-4-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R,4R)-3-cyano-4-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[4-chloro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-(difluoromethyl)-3-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S)-3-(difluoromethyl)-3-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{3-[(1S)-1-hydroxyethyl]-1H-pyrazol-1-yl}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{3-[(1R)-1-hydroxyethyl]-1H-pyrazol-1-yl}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[3-(hydroxymethyl)azetidin-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-(hydroxymethyl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S)-3-(hydroxymethyl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[4-(hydroxymethyl)-2H-1,2,3-triazol-2-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R,5S)-3,5-dihydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2S,5R)-5-hydroxy-2,5-dimethylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2S,5S)-5-hydroxy-2,5-dimethylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;(4S)-2-amino-3'-[4-(3-cyano-1H-pyrazol-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[8-(methoxyimino)-3-azabicyclo[3.2.1]octan-3-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-methyl-2H-1,2,3-triazole-4-carboxamide; 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N-methyl-1H-1,2,3-triazole-4-carboxamide; (4S)-2-amino-3'-[4-(4-cyano-1H-pyrazol-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[4-(methoxyimino)piperidin-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-pyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[3-(1-methyl-1H-pyrazol-3-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-4-[(3R)-3-hydroxy-3- methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidine-3-carboxamide; (4S)-2-amino-3'-[4-(4-aminopiperidin-1-yl)-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(1R,5S,8R)-8-amino-3-azabicyclo[3.2.1]octan-3-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(1R,5S,8S)-8-amino-3-azabicyclo[3.2.1]octan-3-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R,5S)-3-hydroxy-5-methoxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(6S)-6-hydroxy-5,6-dihydrocyclopenta[c]pyrazol-2(4H)-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(6R)-6-hydroxy-5,6-dihydrocyclopenta[c]pyrazol-2(4H)-yl]-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4R)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[3-(hydroxymethyl)-1H-pyrrol-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-cyano-4-[(2-hydroxy-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-[1-(2-hydroxyethyl)-1H-pyrazol-3-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[6-(hydroxymethyl)pyridin-2-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[5-fluoro-3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(6-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-9-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-9H-purin-2-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(7R)-7-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(7S)-7-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- (2H3)methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4R)-2-amino-3'-(1-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-4-[(3R)-3-hydroxy-3- methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-4-[(3R)-3-hydroxy-3- methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; 1-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-1H-pyrazole-3-sulfonamide;(4S)-2-amino-3'-(1-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(3R)-3- hydroxy-3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro- 4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-7-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-7-{(1R)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2-cyano-2-methylpropyl)(methyl)amino]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R,5S)-5-fluoro-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S,5S)-5-fluoro-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 6,7-dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3- carbonitrile; (4S)-2-amino-3'-(4-[(3R,5S)-3,5-dihydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3S,4R)-3-cyano-4-hydroxypiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-4-[(3R)-3-hydroxy-3- methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-pyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-chloro-4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[3-cyano-4-(2-hydroxy-2-methylpropoxy)-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-cyano-4-[3-(hydroxymethyl)-1H-pyrazol-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-cyano-1-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-4-[(3R)-3-hydroxy- 3-methylpiperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-cyano-4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)- pyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[2-(hydroxymethyl)-1H-pyrrol-1-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a-hexaazadibenzo[cd,f]azulen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4R)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2- yl]-4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3- carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3- carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-pyrrolidin-2-yl]ethyl}- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10S)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-pyrrolidin-2-yl]ethyl}- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-10-hydroxy-10- methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-10- hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(2R,3S)-3-fluoro-1-methylpyrrolidin-2-yl]ethyl}-10- hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-4-{(1S)-1-[(2R,3S)-3-methoxy-1-methylpyrrolidin- 2-yl]ethyl}-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11- hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7a,8,9,10,11,12- hexahydro-4H,7H-6-oxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,11,12- hexahydro-4H-6,10-dioxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;(4S)-2-amino-3'-[(7aS)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,11,12- hexahydro-4H-6,10-dioxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7a,8,11,12- tetrahydro-4H,7H,10H-6,9-dioxa-1,3,4,5,12a-pentaazaindeno[7,1-ab]heptalen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-4,7a,8,9,10,11-hexahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-thia-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2- yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-4-[(2-hydroxy- 2-methylpropyl)(methyl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4R)-2-amino-3'-(7-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-3-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-4',5',6,7-tetrahydro- 5H-spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-7-[(3R)-3- hydroxy-3-methylpiperidin-1-yl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4R)-2-amino-3'-(3-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-7-[(3R)-3- hydroxy-3-methylpiperidin-1-yl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-4',5',6,7- tetrahydro-5H-spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(7-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-3-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-6,7-dihydro- 4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-{(1S)-1-[(2S,4R)-4-fluoro-1-methylpyrrolidin-2-yl]ethyl}-7-[(3R)-3- hydroxy-3-methylpiperidin-1-yl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)-6,7-dihydro- 4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylazetidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1,4,4-trimethylazetidin- 2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2- yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-4-[(2S)-1-(dimethylamino)propan-2-yl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-6,6-dioxo-4,6,7,7a,8,9,10,11-octahydro-6λ6-thia-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(3aS,7S,7aS)-1-methyloctahydro-1H- indol-7-yl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(3aS,7R,7aS)-1- methyloctahydropyrano[4,3-b]pyrrol-7-yl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-3'-(4-hydroxy-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-2-{[(1H-pyrrol-2-yl)methyl]amino}-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(6aR,9R)-9-hydroxy-9-methyl-6-methylidene-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-6,6a,7,8,9,10-hexahydro-4H-1,3,4,5,10a- pentaazaacephenanthrylen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[3-cyano-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(piperidin-1-yl)- 1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{4-[(3R)-3-hydroxy-3-methylpiperidin-1-yl]-1-[(3aS,7S,7aS)-1-methyloctahydro-1H-indol-7-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[1-(2-hydroxy-2-methylpropyl)-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethoxy}-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(3S,7aR)-hexahydro-1H-pyrrolizin-3-yl]ethyl}-10- hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(3S,7aS)-hexahydro-1H-pyrrolizin-3-yl]ethyl}-10- hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(2S,3S)-3-(pyrrolidin-1-yl)butan-2- yl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(2R,3R)-3-(pyrrolidin-1-yl)butan-2- yl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(2S)-1-(pyrrolidin-1-yl)propan-2-yl]- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-4-[(2S,3S)-3-(azetidin-1-yl)butan-2-yl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-4-[(2R,3R)-3-(azetidin-1-yl)butan-2-yl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-7-oxo-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a-hexaazadibenzo[cd,f]azulen-2- yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile;(4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-6,10-dimethyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-7-oxo-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a-hexaazadibenzo[cd,f]azulen-2- yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)- pyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-{1-[(1r,3S)-3-hydroxycyclobutyl]-1H-pyrazol-3-yl}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-{1-[(1s,3R)-3-hydroxycyclobutyl]-1H-pyrazol-3-yl}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-methyl-1H- pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-methyl-1H- pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{4-[(6R)-7-amino-6-methyl-1,3,4,6-tetrahydro-5H-pyrido[3,4- f][1,4]oxazocin-5-yl]-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl}-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-{1-[(2S)-2-hydroxypropyl]-1H-pyrazol-3-yl}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-{1-[(2R)-2-hydroxypropyl]-1H-pyrazol-3-yl}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl]amino}-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(1R)-1-(2-aminopyridin-3-yl)ethoxy]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(3-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-3-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-4-[(1S,2S)-2-(dimethylamino)cyclopentyl]-10-hydroxy-10- methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-4-[(1R,2R)-2-(dimethylamino)cyclopentyl]-10-hydroxy-10- methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4R)-4-methyl-2,4,6,7- tetrahydro-5H-pyrazolo[4,3-f][1,4]oxazepin-5-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4S)-4-methyl-2,4,6,7- tetrahydro-5H-pyrazolo[4,3-f][1,4]oxazepin-5-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-4-[(1S,2S)-2-(azetidin-1-yl)cyclopentyl]-10-hydroxy-10-methyl- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-4-[(1R,2R)-2-(azetidin-1-yl)cyclopentyl]-10-hydroxy-10- methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl}- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2R)-2-(2-aminopyridin-3-yl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2S)-2-(2-aminopyridin-3-yl)pyrrolidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;(4S)-2-amino-3'-(6-[(2-aminopyridin-3-yl)methyl]-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7R)-7-(2-aminopyridin-3-yl)-6-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7S)-7-(2-aminopyridin-3-yl)-6-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1S)-1-(3-aminopyrazin-2-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(3-aminopyrazin-2-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-6,7-dihydro-4'H,5H,6'H- spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4R)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4',5',6,7-tetrahydro-5H- spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-(6-[(1R)-1-(5-methyl-1H-pyrazol-4-yl)ethyl]-2-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4S)-2-amino-3'-(6-[(1S)-1-(5-methyl-1H-pyrazol-4-yl)ethyl]-2-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4- yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4R)-4-methyl-2,6,7,9- tetrahydropyrazolo[4,3-f][1,4]oxazocin-5(4H)-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;(4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4S)-4-methyl-2,6,7,9- tetrahydropyrazolo[4,3-f][1,4]oxazocin-5(4H)-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4R)-4-methyl-2,4,7,8- tetrahydropyrazolo[3,4-b][1,5]oxazocin-5(6H)-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4S)-4-methyl-2,4,7,8- tetrahydropyrazolo[3,4-b][1,5]oxazocin-5(6H)-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(6-[1-(2-aminopyridin-3-yl)ethyl]-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-2,6,7,8-tetrahydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-4-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(5R)-6-amino-5-methyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin-4(5H)- yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(5S)-6-amino-5-methyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin-4(5H)- yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S,4R)-4- fluoro-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](2-cyanoethyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(6R)-7-amino-6-methyl-1,3,4,6-tetrahydro-5H-pyrido[3,4- f][1,4]oxazocin-5-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](2,2-difluoroethyl)amino}-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 2-[(7R)-4-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-7-methyl-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,8- dihydro-9-oxa-1,2,3,5,6-pentaazabenzo[cd]azulen-6(2H)-yl]-1,4-anhydro-2,3,5-trideoxy-L- threo-pentitol; 2-{4-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,8-dihydro-9-oxa- 1,2,3,5,6-pentaazabenzo[cd]azulen-6(2H)-yl}-1,4-anhydro-2,3,5-trideoxy-L-threo-pentitol; 2-{4-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-2-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-7,8-dihydro-9-oxa- 1,2,3,5,6-pentaazabenzo[cd]azulen-6(2H)-yl}-1,4-anhydro-2,3,5-trideoxy-D-threo-pentitol; (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(1S)-1-(tetrahydro-1H-pyrrolizin- 7a(5H)-yl)ethyl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-{(7aR,10R)-10-hydroxy-10-methyl-4-[(1R)-1-(tetrahydro-1H-pyrrolizin- 7a(5H)-yl)ethyl]-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(6aR,9R)-9-hydroxy-6,9-dimethyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-6,6a,7,8,9,10-hexahydro-4H-1,3,4,5,10a-pentaazaacephenanthrylen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(6S,6aR,9R)-9-hydroxy-6,9-dimethyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-6,6a,7,8,9,10-hexahydro-4H-1,3,4,5,10a-pentaazaacephenanthrylen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(6R,6aR,9R)-9-hydroxy-6,9-dimethyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-6,6a,7,8,9,10-hexahydro-4H-1,3,4,5,10a-pentaazaacephenanthrylen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[2-(2-hydroxy-2-methylpropyl)-6-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-2,6,7,8-tetrahydro-1,2,3,5,6-pentaazaacenaphthylen-4-yl]-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;2-{2-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-9-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-5-oxo-8,9-dihydro- 7H-imidazo[4,5,1-de]pteridin-4(5H)-yl}-1,4-anhydro-2,3,5-trideoxy-L-threo-pentitol; (4S)-2-amino-3'-(9-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(1R,5R)-3- oxabicyclo[3.1.0]hexan-1-yl]-5-oxo-4,5,8,9-tetrahydro-7H-imidazo[4,5,1-de]pteridin-2-yl)- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[4-(2-hydroxy-2-methylpropyl)-9-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-5-oxo-4,5,8,9-tetrahydro-7H-imidazo[4,5,1-de]pteridin-2-yl]-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(9-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-5-oxo-4-[(3R)-oxolan-3-yl]- 4,5,8,9-tetrahydro-7H-imidazo[4,5,1-de]pteridin-2-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4R)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3- carbonitrile; (4S)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 4',5',6,7-tetrahydro-5H-spiro[[1]benzothiophene-4,7'-pyrano[4,3-d][1,2]oxazole]-3- carbonitrile; (4S)-2-amino-3'-{(7aS,10R)-10-hydroxy-10-methyl-4-[(1S)-1-(tetrahydro-1H-pyrrolizin- 7a(5H)-yl)ethyl]-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4S)-2-amino-3'-{(7aS,10R)-10-hydroxy-10-methyl-4-[(1R)-1-(tetrahydro-1H-pyrrolizin- 7a(5H)-yl)ethyl]-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2- yl}-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4S)-2-amino-3'-[(7aR,10S)-4-{(1S)-1-[(2S)-1-ethylpyrrolidin-2-yl]ethyl}-10-hydroxy-10- methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-(3-oxo-2,8-diazaspiro[4.5]decan-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2S,5R)-2-ethyl-5-hydroxy-5-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}(6,6,7,7-2H4)-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen- 2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3- carbonitrile; (4S)-2-amino-3'-[(9R)-9-hydroxy-6,9-dimethyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-7,8,9,10-tetrahydro-4H-1,3,4,5,10a-pentaazaacephenanthrylen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[3-(1-hydroxyethyl)pyridin-2-yl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{1-[(2S)-1-methylazetidin-2-yl]ethyl}- 7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7- tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-(2H3)methyl-4-{(1S)-1-[(2S)-1- (2H3)methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-6-oxo-4,6,7,7a,8,9,10,11-octahydro-6λ4-thia-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2R,4S)-4-cyano-2-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2R,4R)-4-cyano-2-methylpiperidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;(4S)-2-amino-3'-[(7S,7aR,10R)-10-hydroxy-7,10-dimethyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7R,7aR,10R)-10-hydroxy-7,10-dimethyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](methyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1R)-1-(2-aminopyridin-3-yl)ethyl](methyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{ethyl[(1R)-1-(6-hydroxypyridin-3-yl)ethyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{ethyl[(1S)-1-(6-hydroxypyridin-3-yl)ethyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4R)-6-oxa-1- azaspiro[3.5]nonan-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-4-[(4S)-6-oxa-1- azaspiro[3.5]nonan-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(5aR,8R)-8-hydroxy-8-methyl-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-1,3,5,5a,6,7,8,9-octahydro-4-oxa-1,2,9a,10,12-pentaazabenzo[4,5]cycloocta[1,2,3- cd]inden-11-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]- 3-carbonitrile; (4S)-3'-(4-{[(3S)-1-acetylpyrrolidin-3-yl](ethyl)amino}-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-2-amino-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-3'-(4-{[(3R)-1-acetylpyrrolidin-3-yl](ethyl)amino}-1-{(1S)-1-[(2S)-1-methylpyrrolidin- 2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-2-amino-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; 5-(6-[(4S)-2-amino-3-cyano-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazol]-3'-yl]-1-{(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4- d]pyrimidin-4-yl)-N,N,3-trimethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine-2- carboxamide; (4S)-2-amino-3'-(4-[(2R)-2-(hydroxymethyl)-2-methylazetidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-[(2S)-2-(hydroxymethyl)-2-methylazetidin-1-yl]-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-6,7- dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4R)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]-6,7- dihydro-4'H,5H,6'H-spiro[[1]benzothiophene-4,7'-pyrano[3,4-d][1,2]oxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-methylpyrrolidin-2- yl]ethyl}(7,7-2H2)-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aS,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1-(2H3)methylpyrrolidin- 2-yl]ethyl}-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,11a-pentaazadibenzo[cd,f]azulen-2-yl]- 5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl]amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(1S)-1-(2-aminopyridin-3-yl)ethyl](methyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[2,1]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-6-ethyl-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-7-oxo-4,6,7,7a,8,9,10,11-octahydro-1,3,4,5,6,11a- hexaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(3,5-dimethyl-1H-pyrazol-4-yl)methyl](ethyl)amino}-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(2S,5R)-1,5-dimethylpyrrolidin-2-yl]ethyl}-10- hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-4-{(1S)-1-[(2S,5S)-1,5-dimethylpyrrolidin-2-yl]ethyl}-10- hydroxy-10-methyl-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[(2-aminopyridin-3-yl)methyl](ethyl)amino}-1-{(1S)-1-[(2S)-1- methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro-4'H,5H- spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-[(7aR,10R)-10-hydroxy-10-methyl-4-{(1S)-1-[(2S)-1,5,5- trimethylpyrrolidin-2-yl]ethyl}-7,7a,8,9,10,11-hexahydro-4H-6-oxa-1,3,4,5,11a- pentaazadibenzo[cd,f]azulen-2-yl]-5',6,6',7-tetrahydro-4'H,5H-spiro[[1]benzothiophene-4,7'- [1,2]benzoxazole]-3-carbonitrile; (4S)-2-amino-3'-(4-{[1-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl](ethyl)amino}-1-{(1S)-1-[(2S)- 1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile; and (4S)-2-amino-3'-(4-{[(1S)-1-(2-amino-6-methylpyridin-3-yl)ethyl](ethyl)amino}-1-{(1S)-1- [(2S)-1-methylpyrrolidin-2-yl]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-5',6,6',7-tetrahydro- 4'H,5H-spiro[[1]benzothiophene-4,7'-[1,2]benzoxazole]-3-carbonitrile;an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof.

56. A pharmaceutical composition comprising at least one compound of any one of claims 1 to 55, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable excipients.

57. A method of treating disease, such as cancer, comprising administering to a subject in need of such treatment an effective amount of a compound of any one of claims 1 to 55, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 56.

58. A compound of any one of claims 1 to 55, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, for use in a method of treating cancer in a subject.

59. A compound of any one of claims 1 to 55, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, for treating cancer in a subject.

60. Use of a compound of any one of claims 1 to 55, an isotopically labeled form thereof, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating cancer in a subject.

61. A compound of the formulaor a salt thereof, wherein R is H, methyl, isopropyl, or t-butyl.

62. The compound of claim 61, wherein R is H.

63. A method of comprising contacting with , in the presence of one or more solvents,thereby forming a salt of the formulaisolating the salt.

64. The method of claim 63, wherein the one or more solvents is ethanol, hepatane, or a mixture thereof.

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