Substituted aminopyridine compounds as EGFR inhibitors

Abstract

The present invention provides novel aminopyridine compounds that exhibit inhibitory activity against specific mutant forms of EGFR and pharma- ceutically acceptable compositions thereof.

Description

[Technical Field]

[0001] The present invention relates to novel aminopyridine compounds that exhibit inhibitory activity against specific mutant forms of EGFR and pharmaceutically acceptable compositions thereof. [Background technology]

[0002] Another subtype of lung cancer is epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Human EGFR is a membrane-bound receptor tyrosine kinase of the ErbB family. Activation triggers downstream effects through several signaling pathways, including RAS / RAF / MEK / ERK / MAPK and PI3K / PTEN / Akt / mTOR (Chen et al., 2020). The EGFR signaling pathway regulates a series of critical events that regulate cell-cell communication during development, including proliferation, migration, differentiation, and apoptosis (Wee et al., 2017; Huang et al., 2015; Yewale et al., 2013).

[0003] Approximately 10%–50% of NSCLC patients harbor EGFR-activating mutations, such as in-frame deletions of exon 19 (Del19) and missense mutations in exon 21 (L858R) ( Yang et al., 2018 ; Shigematsu et al., 2005 ; Shu et al., 2017 ; Zhang et al., 2010 ). These patients are treated with gefitinib (IRESSA). TM ), erlotinib (TARCEVA TM ), afatinib (GIOTRIF TMEGFR tyrosine kinase inhibitors (TKIs), such as EGFR-1, respond well to first- and second-generation TKIs and can be used as initial treatment for patients with advanced NSCLC harboring common EGFR mutations (Kashima et al., 2020; Mok et al., 2009; Zhou et al., 2011; Sequist et al., 2013). However, eventual acquired resistance to treatment with gefitinib or erlotinib is primarily caused by mutation of the gatekeeper residue T790M, which is detected in approximately half of clinically resistant patients, resulting in double mutants, L858R / T790M and Del19 / T790M.

[0004] To overcome this resistance, several third-generation EGFR TKIs have been investigated. Currently, osimertinib is the only third-generation EGFR TKI approved by major regulatory agencies for the treatment of T790M-positive patients who have progressed on first- or second-generation EGFR TKIs (Leonetti et al., 2019; Soria et al., 2018).

[0005] Osimertinib is a potent inhibitor of EGFR mutations and the T790M resistance mutation, but it causes ineffective binding and subsequent C797S resistance in patients with NSCLC (Arulananda et al., 2017). Unfortunately, acquired resistance mutations have been reported in lung cancer patients after treatment with third-generation EGFR TKIs. The C797S mutation frequently occurs after the use of third-generation EGFR TKIs in 10%–30% of these patients (Ramalingam et al., 2018; Thress et al., 2015; Oxnard et al., 2018; Starrett et al., 2020; Mehlman et al., 2019; Rangachari et al., 2019; Zhou et al., 2019). Osimertinib resistance due to EGFR triple mutations (Del19 / T790M / C797S and L858R / T790M / C797S) has been reported, and next-generation EGFR-TKIs are required to overcome osimertinib-resistant EGFR triple mutations ( Kashima et al., 2020 ).

[0006] During first-line treatment with third-generation TKIs, C797S develops in the absence of T790M (Chen et al., 2020). Osimertinib was also approved in 2018 as first-line therapy for locally advanced or metastatic EGFR-mutant NSCLC, regardless of T790M mutation status (Leonetti et al., 2019). When osimertinib was administered as frontline treatment, the frequency of C797S mutation was 7%, making it the second most common mechanism of drug resistance in this setting after MET amplification (Leonetti et al., 2019; Ramalingam et al., 2018).

[0007] When osimertinib was administered as a first-line treatment, the most common resistance mechanisms were C797S mutation (7%) and MET amplification (15%). Other mechanisms included HER2 amplification, PIK3CA, and RAS mutations (Ramalingam et al., 2018). Selectivity for wild-type (WT) EGFR is also important for EGFR-TKIs because inhibition of WT EGFR causes side effects such as rash and diarrhea, and these WT EGFR-related toxicities are dose-limiting (Kashima et al., 2020; Fakih et al., 2010; Takeda et al., 2015).

[0008] Next-generation EGFR compounds must inhibit Del19 / T790M / C797S, L858R / T790M / C797S, Del19 / C797S, and L858R / C797S and be highly selective against WT EGFR to avoid side effects. Recently, the mutation-selective inhibitors BI-4020 and BLU-945 have been reported as potential therapeutic strategies to overcome the EGFR Del19 / T790M / C797S mutation (Engelhardt et al., 2019; Schalm et al., 2020).

[0009] However, there are no reports that these compounds inhibit Del19 / C797S and L858R / C797S. Therefore, there is an urgent need for novel EGFR-TKIs that are potently effective against EGFR triple / double mutations.

[0010] To address this unmet need, we are developing next-generation TKIs targeting both the C797S triple and double mutants. There is a need to develop novel selective (next-generation) inhibitors for NSCLC patients with advanced or metastatic disease harboring Del19 / T790M / C797S, L858R / T790M / C797S, Del19 / C797S, and L858R / C797S mutations, depending on second-line or first-line use of third-generation EGFR TKIs.

[0011] References Arulananda S, John T, Dobrovic A. et al. Combination Osimertinib and Gefitinib in C797S and T790M EGFR-Mutated Non-Small Cell Lung Cancer. Journal of Thoracic Oncology Vol. 12 No. 11: 1728-1732, 2017. Chen JS, Riess JW. Advances in targeting acquired resistance mechanisms to epidermal growth factor receptor tyrosine kinase inhibitors. Justin A. Chen, Jonathan W. Riess. J Thorac Dis 2020; 12(5):2859-2876. Engelhardt H, et al. Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors. Cite This: J. Med. Chem. 2019, 62, 10272-10293. Fakih M, Vincent M. Adverse events associated with anti-EGFR therapies for the treatment of metastatic colorectal cancer. Curr. Oncol. 2010; 17: S18-30. Huang L, Fu L. Mechanisms of resistance to EGFR tyrosine kinase inhibitors. Acta Pharm Sin B 2015; 5:390-401. Kashima K, et al. CH7233163 Overcomes Osimertinib-Resistant EGFR-Del19 / T790M / C797S Mutation. Mol Cancer Ther; 19(11) November 2020. Leonetti A, et al. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. British Journal of Cancer (2019) 121:725-737. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-57. Mehlman C, Cadranel J, Rousseau-Bussac G, Lacave R, Pujals A, Girard N, et al. Resistance mechanisms to osimertinib in EGFR-mutated advanced non-smallcell lung cancer: A multicentric retrospective French study. Lung Cancer 2019; 137:149-56. Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, et al. Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib. JAMA Oncol. 2018; 4:1527-34. Ramalingam SS, Yang JC, Lee CK, Kurata T, Kim DW, John T, et al. Osimertinib as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer. J. Clin. Oncol. 2018; 36:841-9. Rangachari D, To C, Shpilsky JE, VanderLaan PA, Kobayashi SS, MushajiangM, et al. EGFR-mutated lung cancers resistant to osimertinib through EGFR C797S respond to first-generation reversible EGFR inhibitors but eventually acquire EGFR T790M / C797S in preclinical models and clinical samples. J. Thorac. Oncol. 2019; 14:1995-2002. Schalm S, et al. BLU-945, a highly potent and selective 4th-generation EGFR TKI for the treatment of EGFR+ / T790M / C797S resistant NSCLC. 2020, ESMO. Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J. Clin. Oncol. 2013; 31:3327-34. Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005; 97:339-46. Shu Y, WuX, Tong X, WangX, Chang Z, MaoY, et al. Circulating tumor DNA mutation profiling by targeted next generation sequencing provides guidance for personalized treatments in multiple cancer types. Sci Rep 2017; 7:583. Soria, J.-C., Ohe, Y., Vansteenkiste, J., Reungwetwattana, T., Chewaskulyong, B., Lee, K. H. et al. Osimertinib in untreated EGFR -mutated advanced non-small cell lung cancer. N. Engl. J. Med 378, 113-125 (2018). Starrett JH,Guernet AA, CuomoME, Poels KE, van Alderwerelt van Rosenburgh IK, Nagelberg A, et al. Drug sensitivity and allele-specificity of first-line osimertinib resistance EGFR mutations. Cancer Res 2020; 80:2017-30. Takeda M, Okamoto I, Nakagawa K. Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Lung Cancer 2015; 88:74-9. Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D, Dougherty B, et al. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med 2015; 21:560-2. Wee, P.; Wang, Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers 2017, 9, 52. Yewale C, Baradia D, Vhora I, et al. Epidermal growth factor receptor targeting in cancer: a review of trends and strategies. Biomaterials 2013; 34:8690-707. Yang Z, Yang N, et al. Investigating Novel Resistance Mechanisms to Third-Generation EGFR Tyrosine Clin Cancer Res; 2018 Zhang Z, Stiegler AL, Boggon TJ, Kobayashi S, Halmos B. EGFR-mutated lung cancer: a paradigm of molecular oncology. Oncotarget 2010; 1:497-514. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomized, phase 3 study. Lancet Oncol. 2011; 12:735-42. Zhou Z, Zhao Y, Shen S, Gu L,Niu Summary of the Invention [Means for solving the problem]

[0012] The present invention relates to novel aminopyridine compounds of formula (I) as shown below, or pharmaceutically acceptable salts thereof: [ka] During the ceremony, R1 is -H; -Si(C 1-6 alkyl)3; OH, halogens, C 1-3 Alkoxy, C 3-6 Cycloalkyl, -NHC 1-6 Alkyl, -NHC 1-6 Haloalkyl, -N(C 1-6alkyl)2, -N(C 1-6 haloalkyl)2, -NHC(O)C 1-6 Alkyl, -NHC(O)C 1-6 Haloalkyl, -NHC(O)C 3-6 Cycloalkyl, -NHC(O)-4 to 7-membered heterocyclyl, -C(O)-4 to 7-membered heterocyclyl, and C 1-6 C optionally or independently substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl, halogen, OH, and oxo. 1-6 alkyl; C 2-5 Alkenyl; -C(O)NHC 1-6 alkyl; -C(O)N(C 1-6 alkyl)2; -C(O)-4 to 7-membered heterocyclyl; -NHC optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen; 1-6 alkyl; -N(C) optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen; 1-6 alkyl)2; and -A-(R 1A ) m is selected from the group consisting of A is C 3-6 Cycloalkyl; C 6-10 aryl; 4- to 8-membered heterocyclyl; and 5- to 10-membered heteroaryl; R 1A teeth, H; OH; NH2; halogen; OH, halogens, C 3-6 Cycloalkyl, -NHC 1-6 Alkyl, -NHC 3-6 Cycloalkyl, -N(C 1-6 alkyl)2, -C(O)N(C 1-6alkyl), -C(O)N-4 to 7-membered heterocyclyl, -NHC(O)C 1-6 Alkyl and halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, and -C(O)C 1-6 C optionally substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of alkyl 1-6 alkyl; OH, halogens, and -N(C 1-6 C optionally substituted with one or more substituents selected from the group consisting of alkyl)2 3-6 cycloalkyl; -C(O)C optionally substituted with one or more substituents selected from the group consisting of OH and halogen 1-6 alkyl; -C(O)N(C 1-6 alkyl)2; -C(O)-4 to 7 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of OH and halogen; 4-7 membered heterocyclyl optionally substituted -NHC 1-6 alkyl; -N(C 1-6 alkyl)2; -S(O)2C 1-6 alkyl; -S(O)2C 3-6 cycloalkyl; oxo; and Halogen, -N(C 1-6 C optionally substituted with alkyl)2 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Haloalkyl, -C(O)C 1-6 4- to 11-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl, and 4- to 7-membered heterocyclyl are independently selected from the group consisting of m is an integer from 0 to 2, R2 is —N(C 1-6 Alkyl)2; OH, halogen, C 3-6 Cycloalkyl, C 1-3 Alkoxy, -NHC 1-6 Alkyl, or -N(C 1-6 -XC optionally substituted with alkyl)2 1-6 Alkyl; and -X(CH2) n -B-(R 2A ) o is selected from the group consisting of X is a bond, —NH—, or —O—; n is an integer from 0 to 1, o is an integer from 0 to 3; B is C 3-7 Cycloalkyl; C 6-10 aryl; 4- to 12-membered heterocyclyl; and 5- to 6-membered heteroaryl; R 2A teeth, H; OH; halogen; OH, halogen, -NHC 1-6 Alkyl, -NHC 1-6 Haloalkyl, -N(C 1-6 alkyl) 2, 4- to 7-membered heterocyclyl, and C 1-3 C optionally or independently substituted with one or more substituents selected from the group consisting of alkoxy 1-6 alkyl; C optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen 3-6 cycloalkyl; C optionally or independently substituted with one or more halogens 1-3 Alkoxy; -C(O)NHC 1-6 alkyl; -C(O)N(C 1-6 alkyl)2; -C(O)NHC 3-6 cycloalkyl; OH, halogens, C 3-6 Cycloalkyl, C1-3 Alkoxy, -NHC 1-6 Alkyl, -N(C 1-6 -NHC optionally or independently substituted with one or more substituents selected from the group consisting of alkyl, 4- to 7-membered heterocyclyl, 1-6 alkyl; -NHC optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen; 3-6 cycloalkyl; -N(C) optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen; 1-6 alkyl)2; -NHC(O)C 1-6 alkyl; -NHC(O)C 3-6 cycloalkyl; -NHS(O)2C 1-6 alkyl; -S(O)2C 1-6 alkyl; Halogens and C 1-6 a 4- to 7-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl; =O; and C(O)C 1-6 Alkyl are independently selected from the group consisting of R3 is YQ-(R 3A ) p and Y is —NH— or a bond; p is an integer from 0 to 2, Q is a 4- to 7-membered heterocyclyl; C 6-10 aryl; and 5- to 6-membered heteroaryl; R 3A H; halogen; halogen and C 3-6 C optionally substituted with one or more substituents selected from the group consisting of cycloalkyl 1-6 Alkyl; C 3-6 Cycloalkyl; 4- to 7-membered heterocyclyl; -S(O)2C optionally substituted with 1 to 3 halogens1-6 Alkyl; —S(O)2C optionally substituted with one or more halogens 3-6 Cycloalkyl; and -S(O)N(C 1-6 alkyl), R4 is H, halogen, and C 1-6 alkyl.

[0013] The present invention also relates to a method of treating a protein kinase mediated disease, particularly a mutant EGFR mediated disease, in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

[0014] The present invention also relates to a pharmaceutically acceptable composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof, which exhibits selective inhibitory activity against at least one mutant EGFR compared to wild-type EGFR. DETAILED DESCRIPTION OF THE INVENTION

[0015] Detailed Description of the Invention The present invention will now be described in more detail.

[0016] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. Also, although the present invention has been described in connection with specific methods and samples, similar or equivalent methods and samples should also fall within the scope of the present invention. Furthermore, unless expressly stated otherwise, numerical values ​​described herein are considered to include the meaning of "about." All publications and other references mentioned herein are incorporated herein by reference in their entirety.

[0017] The definitions of residues used herein are detailed below. Unless otherwise indicated, each residue has the following definition and is used in the sense commonly understood by those skilled in the art.

[0018] As used herein, the terms "halo," "halogen," and "halide" include fluoro, chloro, bromo, and iodo.

[0019] As used herein, "alkyl" refers to an aliphatic hydrocarbon radical and includes both straight-chain and branched-chain hydrocarbon radicals. For example, C 1-6 Alkyl is an aliphatic hydrocarbon having 1 to 6 carbon atoms and includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, and 2-ethylbutyl. Unless otherwise defined, alkyl refers to any of the C 1-6 Alkyl, preferably C 1-4 Alkyl, more preferably C 1-3 refers to alkyl.

[0020] As used herein, "alkenyl" refers to an aliphatic hydrocarbon radical containing at least one carbon-carbon double bond, and includes both straight-chain and branched-chain hydrocarbon radicals. Non-limiting examples of "alkenyl" are vinyl, allyl, but-1-enyl, or but-2-enyl.

[0021] As used herein, "alkynyl" refers to an aliphatic hydrocarbon radical containing at least one carbon-carbon triple bond, and includes both straight-chain and branched-chain hydrocarbon radicals. Non-limiting examples of "alkynyl" are ethynyl, propargyl, but-1-ynyl, or but-2-ynyl.

[0022] As used herein, "haloalkyl" refers to an alkyl group substituted with one or more halogen atoms, where alkyl is defined as above. "Halo" refers to F, Cl, Br, or I, and this term is used interchangeably with "halogen." Unless otherwise defined, haloalkyl refers to fluoromethyl, difluoromethyl, chloromethyl, trifluoromethyl, or 2,2,2-trifluoroethyl.

[0023] As used herein, the term "alkoxy" refers to an -O-alkyl or alkyl-O- group, where the alkyl group is defined as above. For example, it includes methoxy, ethoxy, n-propoxy, n-butoxy, and t-butoxy.

[0024] As used herein, the terms "hydroxy" or "hydroxyl," alone or in combination with other terms, mean --OH.

[0025] As used herein, the term "hydroxyalkyl" refers to any hydroxyl derivative of an alkyl radical. The term "hydroxyalkyl" includes any alkyl radical in which one or more hydrogen atoms have been replaced with a hydroxy group.

[0026] As used herein, "amino" refers to --NH.sub.2.

[0027] As used herein, the term "cycloalkyl" refers to a substituted or unsubstituted cyclic alkyl, such as C 3-20 Cycloalkyl refers to a monovalent saturated hydrocarbon ring system having 3 to 20 carbon atoms. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like. Preferably, unless otherwise defined, cycloalkyl refers to a C 3-8 Cycloalkyl or C 3-6 It may be cycloalkyl.

[0028] As used herein, the term "aryl" refers to an aromatic ring system derived by removing one hydrogen atom from a single carbon atom of a parent aromatic ring system, e.g., 6 to 20 carbon atoms (C 6-20 ) refers to a monovalent aromatic hydrocarbon having a carbon atom or carbonyl group. Aryl may include bicyclic radicals containing an aromatic ring fused to a saturated or partially unsaturated ring. Exemplary aryl groups may include radicals derived from benzene (phenyl), substituted phenyl, biphenyl, naphthyl, toluyl, naphthalenyl, anthracenyl, indenyl, indanyl, and the like. Unless otherwise defined, aryl refers to any radical having a carbon atom or carbonyl group, including C 6-12 Aryl, preferably C 6-10 Refers to aryl.

[0029] As used herein, "heterocyclyl" refers to an aromatic, saturated or partially unsaturated, monocyclic, bicyclic, or polycyclic ring system containing the specified number of ring atoms and including one or more heteroatoms selected from N, O, and S, where the heterocyclyl ring is connected to the base molecule through a C or N ring atom. Bicyclic ring systems may be connected via 1,1-fused (spiro), 1,2-fused (fused), or 1,2-fused (bridgehead).

[0030] As used herein, "heteroaryl" refers to a monovalent or divalent substituent derived from a mono- or polyheterocyclic aromatic hydrocarbon having 1 to 10 carbon ring members and containing one or more, preferably 1 to 3, heteroatoms selected from N, O, and S. Examples of heteroaryl include, but are not limited to, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,2,4-oxadiazolyl, 1,1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, triazolyl, tetrazolyl, triazinyl, indolyl, and the like. Examples of bicyclic heteroaryls include, but are not limited to, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, benzthiadiazolyl, quinolinyl, isoquinolinyl, furopyridinyl, and the like. Unless otherwise defined, heteroaryl is a 4- to 12-membered heteroaryl, preferably a 4- to 10-membered heteroaryl, and more preferably a 4- to 7-membered heteroaryl.

[0031] As used herein, "heterocycloalkyl" refers to a monocyclic, bicyclic, tricyclic or higher cyclic alkyl having 3 to 10 carbon ring members and containing one or more, for example, 1 to 4 heteroatoms selected from N, O, and S. Heterocycloalkyls according to the present invention may also be fused or bridged heterocycloalkyls. Examples of non-aromatic rings include, but are not limited to, azetidinyl, oxetanyl, tetrahydrothienyl, tetrahydrofuranyl, pyrrolinyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, oxazolinyl, oxazolidinyl, oxapiperazinyl, oxapiperidinyl, pyrazolinyl, pyrazolidinyl, thiazolinyl, thiazolidinyl, tetrahydroisothiazolyl, tetrahydrooxazolyl, tetrahydroisoxazolyl, piperidinyl, piperazinyl, tetrahydropyranyl, dihydropyranyl, tetrahydropyridinyl, dihydropyridinyl, dihydrothiopyranyl, tetrahydropyrimidinyl, tetrahydropyridazinyl, dihydropyranyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydropyrazolopyridinyl, morpholinyl, indolinyl, thiomorpholinyl, azepanyl, diazepanyl, azaadamantanyl, diazamantanyl, and the like. Attachment of a heterocycloalkyl substituent can occur via a carbon atom or a heteroatom. A heterocycloalkyl group may be optionally substituted with one or more suitable groups via one or more of the aforementioned groups. Unless otherwise defined, heterocycloalkyl refers to a 4- to 12-membered heterocycloalkyl, preferably a 4- to 10-membered heterocycloalkyl, and more preferably a 4- to 7-membered heterocycloalkyl.

[0032] The present invention provides novel compounds, pharmaceutically acceptable salts, diastereomers, enantiomers, racemates, tautomers, prodrugs, hydrates and solvates thereof, which are useful for inhibiting epidermal growth factor receptor (EGFR) and for treating diseases and disorders mediated by protein kinases, e.g., cell proliferative diseases and disorders such as cancer, immune diseases such as arthritis, rheumatoid arthritis or autoimmune diseases, infectious diseases, cardiovascular diseases, and neurodegenerative diseases and disorders.

[0033] The present invention also provides pharmaceutical compositions comprising at least one compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient.

[0034] The present invention provides compositions and methods for modulating the activity of epidermal growth factor receptor (EGFR) mutants. In one aspect, the present invention provides compounds that act as inhibitors of EGFR mutants.

[0035] In one embodiment, provided herein is a compound of Formula (I) as shown below, a pharmaceutically acceptable salt, diastereomer, enantiomer, racemate, tautomer, prodrug, hydrate, or solvate thereof: [ka] During the ceremony, R1 is -H; -Si(C 1-6 alkyl)3; OH, halogens, C 1-3 Alkoxy, C 3-6 Cycloalkyl, -NHC 1-6 Alkyl, -NHC 1-6 Haloalkyl, -N(C 1-6 alkyl)2, -N(C 1-6 haloalkyl)2, -NHC(O)C 1-6 Alkyl, -NHC(O)C 1-6 Haloalkyl, -NHC(O)C 3-6 Cycloalkyl, -NHC(O)-4 to 7-membered heterocyclyl, -C(O)-4 to 7-membered heterocyclyl, and C 1-6 C optionally or independently substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl, halogen, OH, and oxo. 1-6 alkyl; C 2-5 Alkenyl; -C(O)NHC 1-6 alkyl; -C(O)N(C 1-6 alkyl)2; -C(O)-4 to 7-membered heterocyclyl; -NHC optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen; 1-6 alkyl; -N(C) optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen; 1-6 alkyl)2; and -A-(R 1A ) m is selected from the group consisting of A is C 3-6 Cycloalkyl; C 6-10 aryl; 4- to 8-membered heterocyclyl; and 5- to 10-membered heteroaryl; R 1A teeth, H; OH; NH2; halogen; OH, halogens, C 3-6 Cycloalkyl, -NHC 1-6 Alkyl, -NHC 3-6 Cycloalkyl, -N(C 1-6 alkyl)2, -C(O)N(C 1-6 alkyl), -C(O)N-4 to 7-membered heterocyclyl, -NHC(O)C 1-6 Alkyl and halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, and -C(O)C 1-6 C optionally substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of alkyl 1-6 alkyl; OH, halogens, and -N(C 1-6 C optionally substituted with one or more substituents selected from the group consisting of alkyl)2 3-6 cycloalkyl; -C(O)C optionally substituted with one or more substituents selected from the group consisting of OH and halogen 1-6 alkyl; -C(O)N(C 1-6 alkyl)2; -C(O)-4 to 7 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of OH and halogen; 4-7 membered heterocyclyl optionally substituted -NHC 1-6 alkyl; -N(C 1-6 alkyl)2; -S(O)2C 1-6 alkyl; -S(O)2C 3-6 cycloalkyl; oxo; and Halogen, -N(C 1-6 C optionally substituted with alkyl)2 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Haloalkyl, -C(O)C 1-6 4- to 11-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl, and 4- to 7-membered heterocyclyl are independently selected from the group consisting of m is an integer from 0 to 2, R2 is —N(C 1-6 Alkyl)2; OH, halogen, C 3-6 Cycloalkyl, C 1-3 Alkoxy, -NHC 1-6 Alkyl, or -N(C 1-6 -XC optionally substituted with alkyl)2 1-6 Alkyl; and -X(CH2) n -B-(R 2A ) o is selected from the group consisting of X is a bond, —NH—, or —O—; n is an integer from 0 to 1, o is an integer from 0 to 3; B is C 3-7Cycloalkyl; C 6-10 aryl; 4- to 12-membered heterocyclyl; and 5- to 6-membered heteroaryl; R 2A teeth, H; OH; halogen; OH, halogen, -NHC 1-6 Alkyl, -NHC 1-6 Haloalkyl, -N(C 1-6 alkyl) 2, 4- to 7-membered heterocyclyl, and C 1-3 C optionally or independently substituted with one or more substituents selected from the group consisting of alkoxy 1-6 alkyl; C optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen 3-6 cycloalkyl; C optionally or independently substituted with one or more halogens 1-3 Alkoxy; -C(O)NHC 1-6 alkyl; -C(O)N(C 1-6 alkyl)2; -C(O)NHC 3-6 cycloalkyl; OH, halogens, C 3-6 Cycloalkyl, C 1-3 Alkoxy, -NHC 1-6 Alkyl, -N(C 1-6 -NHC optionally or independently substituted with one or more substituents selected from the group consisting of alkyl, 4- to 7-membered heterocyclyl, 1-6 alkyl; -NHC optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen; 3-6 cycloalkyl; -N(C) optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen; 1-6 alkyl)2; -NHC(O)C 1-6 alkyl; -NHC(O)C 3-6 cycloalkyl; -NHS(O)2C 1-6 alkyl; -S(O)2C 1-6 alkyl; Halogens and C 1-6 a 4- to 7-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl; =O; and C(O)C 1-6 Alkyl are independently selected from the group consisting of R3 is YQ-(R 3A ) p and Y is —NH— or a bond; p is an integer from 0 to 2, Q is a 4- to 7-membered heterocyclyl; C 6-10 aryl; and 5- to 6-membered heteroaryl; R 3A H; halogen; halogen and C 3-6 C optionally substituted with one or more substituents selected from the group consisting of cycloalkyl 1-6 Alkyl; C 3-6 Cycloalkyl; 4- to 7-membered heterocyclyl; -S(O)2C optionally substituted with 1 to 3 halogens 1-6 Alkyl; —S(O)2C optionally substituted with one or more halogens 3-6 Cycloalkyl; and -S(O)N(C 1-6 alkyl), R4 is H, halogen, and C 1-6 alkyl.

[0036] In certain embodiments, R is H; Si(C 1-3 alkyl)3; OH, F, Cl, C 1-3 Alkoxy, -NHC 1-4 Alkyl, -NHC 1-4 Haloalkyl, -N(C 1-4 alkyl)2, -N(C 1-4haloalkyl)2, -NHC(O)C 1-4 Alkyl, -NHC(O)C 3-6 Cycloalkyl, -NHC(O)-4- to 6-membered heterocyclyl, -C(O)-4- to 6-membered heterocyclyl having 1 to 3 heteroatoms selected from the group consisting of N, O, and S, and C 1-4 C optionally or independently substituted with 1 to 3 substituents selected from the group consisting of 4-6 membered heterocyclyl having 1 to 3 heteroatoms selected from the group consisting of N, O, and S, which are optionally or independently substituted with 1 to 3 substituents selected from the group consisting of alkyl, F, Cl, OH, and oxo. 1-4 Alkyl; C 2-5 Alkenyl; -C(O)NHC 1-6 Alkyl; -C(O)N(C 1-4 alkyl); —C(O)-4- to 6-membered heterocyclyl having 1 to 3 heteroatoms selected from the group consisting of N, O, and S; —NHC optionally or independently substituted with 1 to 3 substituents selected from the group consisting of OH, F, and Cl. 1-4 alkyl; —N(C) optionally or independently substituted with 1 to 3 substituents selected from the group consisting of OH, F, and Cl; 1-4 alkyl)2; and A-(R 1A ) m is selected from the group consisting of:

[0037] In more particular embodiments, R1 is -H; -Si(C 1-6 Alkyl)3; OH, halogen, C 1-3 Alkoxy, -NHC(O)C 1-6 C optionally or independently substituted with one or more substituents selected from the group consisting of haloalkyl, -NHC(O)-4- to 7-membered heterocyclyl, -C(O)-4- to 7-membered heterocyclyl, and 4- to 7-membered heterocyclyl optionally or independently substituted with oxo. 1-6 Alkyl; C 2-5 alkenyl; and -A-(R 1A ) m is selected from the group consisting of:

[0038] In the above embodiments of R1, the 4- to 7-membered heterocyclyl may be selected from the group consisting of morpholinyl, pyrrolidinyl, 1,1-dioxo-1,4-thiazinanyl, and oxetanyl.

[0039] In certain embodiments, A is C 3-6 It is selected from the group consisting of cycloalkyl; phenyl; 4- to 7-membered heterocycloalkyl; 5- to 6-membered heteroaryl; and 9- to 10-membered heteroaryl.

[0040] In a more particular embodiment, A is C 3-6 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl; triazolyl; thiazolyl; pyrazinyl; tetrahydropyranyl, pyrrolidinyl, piperidinyl, thienyl, pyrimidinyl, tetrahydrofuranyl, imidazolyl, pyrrolyl, pyrrolo[3,2-c]pyridinyl, oxetanyl, 7-oxabicyclo[2.2.1]heptanyl, and 1,1-dioxo-thiolanyl.

[0041] In certain embodiments, R 1A are H; OH; NH2; F; Cl; OH, F, Cl, C 3-6 Cycloalkyl, -NHC 1-4 Alkyl, -NHC 3-4 Cycloalkyl, -N(C 1-4 alkyl)2, -C(O)N(C 1-4 alkyl), —C(O)N-4- to 7-membered heterocyclyl having 1 to 3 heteroatoms selected from the group consisting of N, O, and S; —NHC(O)C 1-4 Alkyl, F, Cl, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Hydroxyalkyl, and -C(O)C 1-4C optionally substituted with 1 to 3 substituents selected from the group consisting of 4-7 membered heterocyclyl having 1 to 3 heteroatoms selected from the group consisting of N, O, and S, optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl 1-4 Alkyl; OH, F, Cl, and -N(C 1-4 C optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl)2 3-6 Cycloalkyl; —C(O)C optionally substituted with 1 to 3 substituents selected from the group consisting of OH, F, and Cl. 1-6 Alkyl; -C(O)N(C 1-4 alkyl); -C(O)-4- to 7-membered heterocyclyl having 1 to 3 heteroatoms selected from the group consisting of N, O, and S, optionally substituted with 1 to 3 OH; -NHC optionally substituted with 4 to 7-membered heterocyclyl having 1 to 3 heteroatoms selected from the group consisting of N, O, and S. 1-6 Alkyl; -N(C 1-6 alkyl)2;-S(O)2C 1-6 Alkyl; -S(O)2C 3-6 Cycloalkyl; and F, Cl, -N(C 1-4 C optionally substituted with alkyl)2 1-4 Alkyl, C 3-6 Cycloalkyl, C 1-4 Haloalkyl, -C(O)C 1-4 and 4- to 11-membered heterocyclyl optionally or independently substituted with 1 to 3 substituents selected from the group consisting of alkyl, and 4- to 7-membered heterocyclyl having 1 to 3 heteroatoms selected from the group consisting of N, O, and S.

[0042] In more particular embodiments, R 1A OH, halogen, C 3-6 Cycloalkyl, -NHC 1-6 Alkyl, -NHC 3-6 Cycloalkyl, -N(C 1-6 alkyl)2, -C(O)N(C 1-6alkyl), -C(O)N-4 to 7-membered heterocyclyl, -NHC(O)C 1-6 Alkyl and halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, and -C(O)C 1-6 C optionally substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of alkyl 1-6 Alkyl; OH, halogen, and -N(C 1-6 C optionally substituted with one or more substituents selected from the group consisting of alkyl)2 3-6 cycloalkyl; and halogen, -N(C 1-6 C optionally substituted with alkyl)2 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Haloalkyl, -C(O)C 1-6 and 4- to 7-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl, and 4- to 7-membered heterocyclyl.

[0043] In another more particular embodiment, R 1A teeth, H; OH; NH2; halogen; OH, halogens, C 3-6 Cycloalkyl, -N(C 1-6 alkyl)2, -C(O)N(C 1-6 alkyl)2, and halogen and C 1-6 C optionally substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of alkyl 1-6 alkyl; C optionally substituted with one or more halogens 3-6 cycloalkyl; -C(O)C optionally substituted with one or more halogens 1-6 alkyl; -C(O)N(C 1-6 alkyl)2; -C(O)-4 to 7 membered heterocyclyl optionally substituted with one or more OH; 4-7 membered heterocyclyl optionally substituted -NHC 1-6 alkyl; -S(O)2C 1-6 alkyl; -S(O)2C 3-6 cycloalkyl; and C 1-6 Alkyl and -C(O)C 1-6 4- to 11-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl is selected from the group consisting of:

[0044] R 1A In the above embodiments, the 4-7 membered heterocyclyl or the 4-11 membered heterocyclyl may be selected from the group consisting of tetrahydropyranyl, piperidinyl, azetidinyl, morpholinyl, piperazinyl, dioxanyl, tetrahydrofuranyl, and oxetanyl.

[0045] In certain embodiments, R2 is —N(C 1-6 alkyl)2; OH, F, Cl, C 3-6 Cycloalkyl, C 1-3 Alkoxy, -NHC 1-4 Alkyl, or -N(C 1-4 -XC optionally substituted with alkyl)2 1-4 alkyl; and X(CH2) n -B-(R 2A ) o wherein X is a bond, —NH—, or —O—; n is an integer of 0 to 1; and o is an integer of 0 to 3.

[0046] In another more particular embodiment, R2 is —N(C 1-6alkyl)2; -XC optionally substituted with OH 1-6 Alkyl; and -X(CH2) n -B-(R 2A ) o is selected from the group consisting of:

[0047] In certain embodiments, B is C 3-6 cycloalkyl; phenyl; 4-11 membered heterocycloalkyl having 1-3 heteroatoms selected from the group consisting of N, O, and S; and 5-6 membered heteroaryl having 1-3 heteroatoms selected from the group consisting of N, O, and S.

[0048] In another more particular embodiment, B is C 3-6 cycloalkyl; phenyl; piperazinyl, piperidinyl, 4-oxopiperidinyl, azaspiro[3.5]nonanyl, pyrrolidinyl, azetidinyl, azepanyl, 2,8-diazaspiro[4.5]decaneonyl, 2,8-diazaspiro[4.5]decanyl, 2,7-diazaspiro[3.5]nonanyl, pyrazolyl, 1-oxa-8-azaspiro[4.5]decanyl, 1-oxa-7-azaspiro[3.5]nonanyl, 3,9-diazaspiro[5.5]undecanyl, 3-azabicyclo[3.1.0]hexanyl, 8-azabicyclo[3.2.1]octanyl, and 1-azaspiro[4.5]decaneonyl.

[0049] In certain embodiments, R 2A are H; OH; F; Cl; OH, F, Cl, -NHC 1-4 Alkyl, -NHC 1-4 Haloalkyl, -N(C 1-4 alkyl)2, and C 1-3 C optionally or independently substituted with 1 to 3 substituents selected from the group consisting of alkoxy 1-6 Alkyl; C optionally substituted with 1 to 3 OH 3-6 Cycloalkyl; C optionally or independently substituted with 1 to 3 substituents selected from the group consisting of F and Cl 1-3Alkoxy; -C(O)NHC 1-4 Alkyl; -C(O)NHC 3-6 Cycloalkyl; OH, F, Cl, C 3-6 Cycloalkyl, C 1-3 Alkoxy, -NHC 1-4 Alkyl, -N(C 1-4 -NHC optionally or independently substituted with one or more substituents selected from the group consisting of alkyl)2, and 4-7 membered heterocyclyl having 1-3 heteroatoms selected from the group consisting of N, O, and S. 1-4 alkyl; -NHC optionally or independently substituted with 1 to 3 substituents selected from the group consisting of OH, F, and Cl; 3-6 Cycloalkyl; —N(C) optionally or independently substituted with 1 to 3 substituents selected from the group consisting of OH, F, and Cl 1-4 alkyl)2;-NHC(O)C 1-4 Alkyl;-NHC(O)C 3-6 Cycloalkyl;-NHS(O)2C 1-4 Alkyl; -S(O)2C 1-4 Alkyl; F, Cl, and C 1-6 4-7 membered heterocyclyl having 1-3 heteroatoms selected from the group consisting of N, O, and S, optionally or independently substituted with 1-3 substituents selected from the group consisting of alkyl; -C(O)C 1-6 alkyl; and =O.

[0050] In more particular embodiments, R 2A OH; halogen; OH, halogen, -NHC 1-6 Alkyl, -NHC 1-6 Haloalkyl, -N(C 1-6 alkyl)2, and C 1-3 C optionally or independently substituted with one or more substituents selected from the group consisting of alkoxy 1-6 Alkyl; C 3-6 Cycloalkyl; OH, halogen, C 3-6 Cycloalkyl, C 1-3 Alkoxy, -NHC 1-6Alkyl, -N(C 1-6 -NHC optionally or independently substituted with one or more substituents selected from the group consisting of alkyl, 4- to 7-membered heterocyclyl, 1-6 alkyl; -NHC optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen; 3-6 cycloalkyl; and —N(C 1-6 alkyl)2.

[0051] In another more particular embodiment, R 2A teeth, H; OH; halogen; OH, halogen, -NHC 1-6 Alkyl, -NHC 1-6 Haloalkyl, and -N(C 1-6 C optionally or independently substituted with one or more substituents selected from the group consisting of alkyl 1-6 alkyl; C optionally or independently substituted with one or more OH 3-6 cycloalkyl; C optionally or independently substituted with one or more halogens 1-3 Alkoxy; OH, halogens, C 3-6 Cycloalkyl, C 1-3 Alkoxy, and -N(C 1-6 -NHC optionally or independently substituted with one or more substituents selected from the group consisting of alkyl 1-6 alkyl; -NHS(O)2C 1-6 alkyl; -S(O)2C 1-6 alkyl; Halogens and C 1-6 a 4- to 7-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl; =O; and C(O)C 1-6 Alkyl are independently selected from the group consisting of:

[0052] R 2A In the above embodiment, the 4-7 membered heterocyclyl may be piperazinyl or azetidinyl.

[0053] In certain embodiments, Q is selected from the group consisting of pyrazolyl, pyridinyl, phenyl, and piperazinyl.

[0054] In certain embodiments, R 3A H; halogens; F, Cl, and C 3-6 C optionally substituted with 1 to 3 substituents selected from the group consisting of cycloalkyl 1-4 Alkyl; C 3-6 Cycloalkyl; 4- to 7-membered heterocyclyl having 1 to 3 heteroatoms selected from the group consisting of N, O, and S; -S(O)2C 1-4 Alkyl; —S(O)2C optionally substituted with 1 to 3 F and Cl 3-6 Cycloalkyl; and -S(O)N(C 1-4 alkyl).

[0055] In more particular embodiments, R3 is a halogen; C optionally substituted with one or more halogens 1-6 Alkyl; -S(O)2C 1-6 Alkyl; -S(O)2C 3-6 cycloalkyl; and -S(O)N(C 1-6 alkyl).

[0056] In certain embodiments, R4 is H.

[0057] Representative compounds of formula (I) are listed below.

[0058] (1) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-methylpiperazin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0059] (2) N 4 -Cyclohexyl-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0060] (3) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(ethylsulfonyl)piperazin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0061] (4) (R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)butan-1-ol;

[0062] (5) (S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-2-methylbutan-2-ol;

[0063] (6) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0064] (7) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-one;

[0065] (8) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoropiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0066] (9) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol;

[0067] (10) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0068] (11) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)propan-2-ol;

[0069] (12) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0070] (13) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0071] (14) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol;

[0072] (15) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-methoxypiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0073] (16) 2-(4-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperazin-1-yl)ethan-1-ol;

[0074] (17) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0075] (18) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0076] (19) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0077] (20) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -isopropylpyridine-2,4-diamine;

[0078] (21) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-(pyridin-3-ylethynyl)pyridine-2,4-diamine;

[0079] (22) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-(4-methoxybut-1-yn-1-yl)pyridine-2,4-diamine;

[0080] (23) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -isopropylpyridine-2,4-diamine;

[0081] (24) N 4 -(sec-butyl)-N 2-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0082] (25) N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0083] (26) N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0084] (27) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0085] (28) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0086] (29) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol;

[0087] (30) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol;

[0088] (31) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol;

[0089] (32) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol;

[0090] (33) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol;

[0091] (34) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol;

[0092] (35) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol;

[0093] (36) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol;

[0094] (37) 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol;

[0095] (38) 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol;

[0096] (39) 3-((2-((2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl)amino)-5-(2-(1-methylpyrazol-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propan-1-ol;

[0097] (40) 3-((2-((2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl)amino)-5-(2-(1-(2-fluoroethyl)pyrazol-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propan-1-ol;

[0098] (41) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0099] (42) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0100] (43) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0101] (44) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0102] (45) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0103] (46) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0104] (47) (1-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0105] (48) (1-(5-((1-(cyclopropylmethyl)-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0106] (49) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0107] (50) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -(4-((dimethylamino)methyl)benzyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0108] (51) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -(4-((dimethylamino)methyl)benzyl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0109] (52) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -(4-((dimethylamino)methyl)benzyl)pyridine-2,4-diamine;

[0110] (53) N 2-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0111] (54) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-isopropoxy-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0112] (55) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-isopropoxypyridin-2-yl)pyrimidin-4-amine;

[0113] (56) N-(4-(sec-butoxy)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0114] (57) N-(4-(sec-butoxy)-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0115] (58) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0116] (59) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0117] (60) N-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0118] (61) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0119] (62) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-(pyridin-3-ylethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0120] (63) N-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanesulfonamide;

[0121] (64) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(isopropylamino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0122] (65) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-(trifluoromethyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0123] (66) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoro-4-(trifluoromethyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0124] (67) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-(trifluoromethoxy)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0125] (68) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3,3-difluoropiperidin-4-ol;

[0126] (69) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3,3-dimethylpiperidin-4-ol;

[0127] (70) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-fluoropiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0128] (71) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(3-(trifluoromethyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0129] (72) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-(fluoromethyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0130] (73) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0131] (74) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -(3-fluorocyclohexyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0132] (75) (1R,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0133] (76) (1R,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0134] (77) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azepan-4-ol;

[0135] (78) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azepan-4-yl)methanol;

[0136] (79) 8-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decan-1-one;

[0137] (80) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((2-fluoroethyl)amino)cyclohexyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0138] (81) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol;

[0139] (82) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0140] (83) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol;

[0141] (84) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0142] (85) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0143] (86) 1-(5-((5-cyclopropyl-1-methyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-ol;

[0144] (87) 2-(1-(5-((5-cyclopropyl-1-methyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0145] (88) (1s,4s)-4-((5-((5-cyclopropyl-1-methyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexan-1-ol;

[0146] (89) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0147] (90) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol;

[0148] (91) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0149] (92) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0150] (93) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-one;

[0151] (94) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0152] (95) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0153] (96) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0154] (97) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoropiperidin-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0155] (98) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-methoxypiperidin-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0156] (99) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0157] (100) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol;

[0158] (101) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0159] (102) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0160] (103) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0161] (104) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0162] (105) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol;

[0163] (106) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0164] (107) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0165] (108) 1-(5-((1-(1-acetylpiperidin-4-yl)-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-one;

[0166] (109) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0167] (110) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0168] (111) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-fluoro-4-(hydroxymethyl)piperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0169] (112) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-fluoropiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0170] (113) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-methoxypiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0171] (114) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0172] (115) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(3-(hydroxymethyl)piperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0173] (116) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0174] (117) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0175] (118) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol;

[0176] (119) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0177] (120) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0178] (121) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0179] (122) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol;

[0180] (123) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0181] (124) N-(4-(4-((cyclopropylmethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0182] (125) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(isopentylamino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0183] (126) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2,2-difluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0184] (127) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-((3,3,3-trifluoropropyl)amino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0185] (128) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(3,3-difluoroazetidin-1-yl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0186] (129) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0187] (130) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-(methylamino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0188] (131) 2-((1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)amino)ethan-1-ol;

[0189] (132) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-methoxyethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0190] (133) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-N 2 ,N 2 -dimethylethane-1,2-diamine;

[0191] (134) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-N 2 ,N 2 ,2-trimethylpropane-1,2-diamine;

[0192] (135) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-((2,2,2-trifluoroethyl)amino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0193] (136) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidin-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0194] (137) 2-((1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)amino)ethan-1-ol;

[0195] (138) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-N 2 ,N 2 -dimethylethane-1,2-diamine;

[0196] (139) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-((2-(dimethylamino)ethyl)amino)piperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0197] (140) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-3-yl)ethynyl)-4-(4-(methylamino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0198] (141) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0199] (142) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-N 2 ,N 2 -dimethylethane-1,2-diamine;

[0200] (143) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-N 2 ,N 2 -dimethylethane-1,2-diamine;

[0201] (144) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)ethynyl)-4-(4-((2-fluoroethyl)amino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0202] (145) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)-4-(4-((2-fluoroethyl)amino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0203] (146) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-methyl-4-((methylamino)methyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0204] (147) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0205] (148) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0206] (149) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0207] (150) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0208] (151) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(2,2-difluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0209] (152) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0210] (153) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-(2-(methylamino)ethyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0211] (154) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(2,8-diazaspiro[4.5]decan-2-yl)pyridin-2-yl)pyrimidin-4-amine;

[0212] (155) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(2,7-diazaspiro[3.5]nonan-2-yl)pyridin-2-yl)pyrimidin-4-amine;

[0213] (156) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(2,8-diazaspiro[4.5]decan-8-yl)pyridin-2-yl)pyrimidin-4-amine;

[0214] (157) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0215] (158) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol;

[0216] (159) (1R,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0217] (160) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0218] (161) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0219] (162) 2-((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexyl)propan-2-ol;

[0220] (163) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0221] (164) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0222] (165) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(3-morpholinoprop-1-yn-1-yl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0223] (166) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(3-morpholinoprop-1-yn-1-yl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol;

[0224] (167) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1,2,4-triazol-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0225] (168) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-ethylthiazol-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0226] (169) (1S,3R)-3-((5-((3-aminophenyl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexan-1-ol;

[0227] (170) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-methylpyrazin-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0228] (171) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(3-(pyrrolidin-1-yl)prop-1-yn-1-yl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0229] (172) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((2-morpholinoethyl)amino)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0230] (173) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-((2-morpholinoethyl)amino)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0231] (174) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridin-3-yl)ethynyl)cyclohexan-1-ol;

[0232] (175) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)cyclohexan-1-ol;

[0233] (176) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-hydroxycyclopentyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0234] (177) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)cyclopentan-1-ol;

[0235] (178) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0236] (179) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0237] (180) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylpyrrolidin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0238] (181) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylpyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0239] (182) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylpiperidin-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0240] (183) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-methyltetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0241] (184) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyridin-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0242] (185) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyridin-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0243] (186) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-(morpholinomethyl)pyridin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0244] (187) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-(morpholinomethyl)pyridin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0245] (188) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(morpholinomethyl)thiazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0246] (189) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(morpholinomethyl)thiazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0247] (190) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)thiophen-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0248] (191) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)thiophen-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0249] (192) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(morpholinomethyl)thiazol-5-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0250] (193) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidin-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0251] (194) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidin-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0252] (195) 4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)tetrahydro-2H-pyran-4-ol;

[0253] (196) 4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridin-3-yl)ethynyl)tetrahydro-2H-pyran-4-ol;

[0254] (197) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0255] (198) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0256] (199) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((2-methylthiazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0257] (200) N 2- (2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((2-(fluoromethyl)thiazol-4-yl)ethynyl)-N 4 -isopropylpyridine-2,4-diamine;

[0258] (201) 4-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(isopropylamino)pyridin-3-yl)prop-2-yn-1-yl)thiomorpholine 1,1-dioxide;

[0259] (202) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-(3-morpholinoprop-1-yn-1-yl)pyridine-2,4-diamine;

[0260] (203) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-(3-(pyrrolidin-1-yl)prop-1-yn-1-yl)pyridine-2,4-diamine;

[0261] (204) 4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(isopropylamino)pyridin-3-yl)-2-methylbut-3-yn-2-ol;

[0262] (205) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((2-cyclopropylthiazol-4-yl)ethynyl)-N 4 -isopropylpyridine-2,4-diamine;

[0263] (206) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridine-2,4-diamine;

[0264] (207) N-(5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(isopropylamino)pyridin-3-yl)pent-4-yn-1-yl)morpholine-4-carboxamide;

[0265] (208) 6-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(isopropylamino)pyridin-3-yl)-1-morpholinohex-5-yn-1-one;

[0266] (209) N-(6-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(isopropylamino)pyridin-3-yl)hex-5-yn-1-yl)morpholine-4-carboxamide;

[0267] (210) 7-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(isopropylamino)pyridin-3-yl)-1-morpholinohept-6-yn-1-one;

[0268] (211) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methylthiazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0269] (212) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(fluoromethyl)thiazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0270] (213) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-imidazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0271] (214) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-1,2,4-triazol-3-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0272] (215) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-morpholinopyridin-3-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0273] (216) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-imidazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0274] (217) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(thiophen-3-ylethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0275] (218) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0276] (219) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-morpholinoethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0277] (220) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol;

[0278] (221) 2-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-hydroxy-4-methylcyclohexyl)amino)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide;

[0279] (222) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methylthiazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclopentan-1-ol;

[0280] (223) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-imidazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclopentan-1-ol;

[0281] (224) 3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-imidazol-4-yl)ethynyl)pyridin-4-yl)amino)-2,2-dimethylpropan-1-ol;

[0282] (225) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(thiophen-3-ylethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0283] (226) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-5-(thiophen-3-ylethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0284] (227) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-morpholinopyridin-3-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0285] (228) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(thiophen-3-ylethynyl)pyridin-4-yl)piperidin-3-ol;

[0286] (229) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(thiophen-3-ylethynyl)pyridin-4-yl)-3,3-dimethylpiperidin-4-ol;

[0287] (230) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(3-methyl-3-morpholinobut-1-yn-1-yl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0288] (231) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0289] (232) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-morpholinoethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0290] (233) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(1-methyl-1H-pyrazol-4-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0291] (234) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;

[0292] (235) N-(4-(1-cyclopropyl-1H-pyrazol-4-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0293] (236) N-(4-(1-cyclopropyl-1H-pyrazol-4-yl)-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0294] (237) N-(4-(1-cyclopropyl-1H-pyrazol-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0295] (238) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((2-methylthiazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0296] (239) 4-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)pyridin-3-yl)prop-2-yn-1-yl)thiomorpholine 1,1-dioxide;

[0297] (240) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-(3-(pyrrolidin-1-yl)prop-1-yn-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0298] (241) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-3-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0299] (242) (1-(5-((1-((1,4-dioxan-2-yl)methyl)-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0300] (243) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydrofuran-3-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0301] (244) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0302] (245) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(oxetan-3-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0303] (246) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((trimethylsilyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0304] (247) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-ethynylpyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0305] (248) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-((3,3-difluoroazetidin-1-yl)methyl)-1-(2,2-difluoroethyl)-1H-pyrrol-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0306] (249) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0307] (250) (1-(5-(cyclopropylethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0308] (251) (1-(5-(cyclopentylethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0309] (252) (1-(5-(cyclohexylethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0310] (253) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0311] (254) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((dimethylamino)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0312] (255) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-((dimethylamino)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0313] (256) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(phenylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0314] (257) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-fluorophenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0315] (258) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-4-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0316] (259) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-2-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0317] (260) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-3-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0318] (261) (3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(morpholino)methanone;

[0319] (262) 4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)-N,N-dimethylbenzamide;

[0320] (263) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(morpholino)methanone;

[0321] (264) 6-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)-N,N-dimethylpicolinamide;

[0322] (265) (6-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)pyridin-2-yl)(morpholino)methanone;

[0323] (266) 2-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)cyclobutyl)propan-2-ol;

[0324] (267) (1-(2-((2-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0325] (268) (4-methyl-1-(2-((2-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol;

[0326] (269) (1-(2-((2-(6-fluoropyridin-3-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0327] (270) (4-methyl-1-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-2-((2-((2-(methylsulfonyl)phenyl)amino)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-yl)methanol;

[0328] (271) (1-(5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)-2-((2-((2-(methylsulfonyl)phenyl)amino)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0329] (272) 4-(4-((4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)amino)pyrimidin-2-yl)-N,N,3-trimethyl-1H-pyrazole-1-sulfonamide;

[0330] (273) 4-(4-((4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)amino)pyrimidin-2-yl)-N,N-dimethyl-1H-pyrazole-1-sulfonamide;

[0331] (274) 4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)but-3-yn-1-ol;

[0332] (275) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(4,4,4-trifluorobut-1-yn-1-yl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0333] (276) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(4-fluorobut-1-yn-1-yl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0334] (277) (1-(5-(but-3-en-1-yn-1-yl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0335] (278) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-((dimethylamino)methyl)pyridin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0336] (279) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-((4-methylpiperazin-1-yl)methyl)pyridin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0337] (280) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-3-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol;

[0338] (281) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-methoxy-4-methylpiperidin-1-yl)-5-(pyridin-3-ylethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0339] (282) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-(pyridin-3-ylethynyl)-4-(1-oxa-8-azaspiro[4.5]decan-8-yl)pyridin-2-yl)pyrimidin-4-amine;

[0340] (283) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-(pyridin-3-ylethynyl)-4-(1-oxa-7-azaspiro[3.5]nonan-7-yl)pyridin-2-yl)pyrimidin-4-amine;

[0341] (284) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)-2-methylpent-4-yn-2-ol;

[0342] (285) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(4-morpholinobut-1-yn-1-yl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0343] (286) 3-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)prop-2-yn-1-yl)oxetan-3-ol;

[0344] (287) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)pent-4-yn-2-ol;

[0345] (288) N-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)prop-2-yn-1-yl)-2,2,2-trifluoroacetamide;

[0346] (289) 4-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)prop-2-yn-1-yl)thiomorpholine 1,1-dioxide;

[0347] (290) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-(trifluoromethyl)-1H-pyrazol-5-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0348] (291) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(trifluoromethyl)thiazol-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0349] (292) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(trifluoromethyl)thiazol-5-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0350] (293) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-fluoropiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine formate;

[0351] (294) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine formate;

[0352] (295) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((dimethylamino)methyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0353] (296) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-methylpiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0354] (297) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)pyridin-2-yl)pyrimidin-4-amine formate;

[0355] (298) N-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)piperidin-1-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0356] (299) N-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-methylpiperidin-1-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0357] (300) N-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-fluoropiperidin-1-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0358] (301) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0359] (302) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-methylpiperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0360] (303) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0361] (304) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-(hydroxymethyl)cyclohexan-1-ol;

[0362] (305) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0363] (306) (1R,3S)-3-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclopentan-1-ol;

[0364] (307) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol;

[0365] (308) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0366] (309) 5-((1-(cyclopropylmethyl)-1H-pyrazol-4-yl)ethynyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine;

[0367] (310) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine;

[0368] (311) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine;

[0369] (312) N 2-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0370] (313) 5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine;

[0371] (314) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0372] (315) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-((dimethylamino)methyl)piperidin-4-ol;

[0373] (316) 1-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-((dimethylamino)methyl)piperidin-4-ol;

[0374] (317) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-((dimethylamino)methyl)piperidin-4-ol;

[0375] (318) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-2-yl)pyrimidin-4-amine;

[0376] (319) N-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0377] (320) N-(5-((1-(cyclopropylmethyl)-1H-pyrazol-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0378] (321) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-2-yl)pyrimidin-4-amine;

[0379] (322) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-2-yl)pyrimidin-4-amine;

[0380] (323) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol;

[0381] (324) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0382] (325) 2-((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)propan-2-ol;

[0383] (326) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol;

[0384] (327) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0385] (328) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0386] (329) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)propan-2-ol;

[0387] (330) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)cyclopropan-1-ol;

[0388] (331) ((1R,5S,6r)-3-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3-azabicyclo[3.1.0]hexan-6-yl)methanol;

[0389] (332) ((1R,3s,5S)-8-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-8-azabicyclo[3.2.1]octan-3-yl)methanol;

[0390] (333) ((1S,5S)-3-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)methanol;

[0391] (334) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-one;

[0392] (335) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0393] (336) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0394] (337) 2-((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)propan-2-ol;

[0395] (338) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0396] (339) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0397] (340) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0398] (341) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0399] (342) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0400] (343) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0401] (344) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol;

[0402] (345) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((2-fluoroethyl)amino)cyclohexyl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0403] (346) 2-((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)propan-2-ol;

[0404] (347) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0405] (348) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0406] (349) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0407] (350) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-methyloxetan-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0408] (351) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)cyclobutan-1-ol;

[0409] (352) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(oxetan-3-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0410] (353) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(oxetan-3-ylethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0411] (354) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)oxetan-3-ol;

[0412] (355) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)tetrahydrofuran-3-ol;

[0413] (356) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridin-3-yl)ethynyl)tetrahydrofuran-3-ol;

[0414] (357) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)tetrahydro-2H-pyran-3-ol;

[0415] (358) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0416] (359) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0417] (360) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0418] (361) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol;

[0419] (362) (5s,8s)-8-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)-1-azaspiro[4.5]decan-2-one;

[0420] (363) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)methyl)-1-methylcyclohexan-1-ol;

[0421] (364) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidin-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol;

[0422] (365) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidin-2-yl)ethynyl)pyridin-4-yl)-4-methoxypiperidin-4-ol;

[0423] (366) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((5-(morpholinomethyl)pyrimidin-2-yl)ethynyl)-4-(1-oxa-8-azaspiro[4.5]decan-8-yl)pyridin-2-yl)pyrimidin-4-amine;

[0424] (367) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((5-(morpholinomethyl)pyrimidin-2-yl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonan-7-yl)pyridin-2-yl)pyrimidin-4-amine;

[0425] (368) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol;

[0426] (369) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methoxypiperidin-4-ol;

[0427] (370) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonan-7-yl)pyridin-2-yl)pyrimidin-4-amine;

[0428] (371) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylpyrrolidin-3-yl)ethynyl)pyridin-4-yl)-4-methoxypiperidin-4-ol;

[0429] (372) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methylpyrrolidin-3-yl)ethynyl)-4-(1-oxa-8-azaspiro[4.5]decan-8-yl)pyridin-2-yl)pyrimidin-4-amine;

[0430] (373) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methylpyrrolidin-3-yl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonan-7-yl)pyridin-2-yl)pyrimidin-4-amine;

[0431] (374) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0432] (375) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol;

[0433] (376) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0434] (377) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)amino)methyl)-1-methylcyclohexan-1-ol;

[0435] (378) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0436] (379) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0437] (380) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)methyl)-1-methylcyclohexan-1-ol;

[0438] (381) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexyl)methanol;

[0439] (382) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoro-4-((methylamino)methyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0440] (383) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoro-4-(((2-fluoroethyl)amino)methyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0441] (384) (S)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-((dimethylamino)methyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0442] (385) (S)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-((dimethylamino)methyl)piperidin-1-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0443] (386) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0444] (387) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0445] (388) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexyl)methanol;

[0446] (389) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0447] (390) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0448] (391) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0449] (392) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexyl)methanol;

[0450] (393) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0451] (394) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0452] (395) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0453] (396) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0454] (397) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0455] (398) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol;

[0456] (399) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0457] (400) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexyl)methanol;

[0458] (401) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0459] (402) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0460] (403) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol;

[0461] (404) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol;

[0462] (405) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexyl)methanol;

[0463] (406) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-methylpiperidin-1-yl)-5-((1-methylcyclopropyl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0464] (407) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-methylcyclopropyl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0465] (408) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one;

[0466] (409) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-((((1r,4r)-4-hydroxycyclohexyl)methyl)amino)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one;

[0467] (410) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-hydroxy-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one;

[0468] (411) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-((((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)amino)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one;

[0469] (412) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-((dimethylamino)methyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one;

[0470] (413) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one;

[0471] (414) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one;

[0472] (415) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one;

[0473] (416) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0474] (417) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol;

[0475] (418) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-methylpiperidin-1-yl)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0476] (419) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0477] (420) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0478] (421) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0479] (422) ((1s,4s)-4-((5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexyl)methanol;

[0480] (423) (1r,4r)-4-(((5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)methyl)cyclohexan-1-ol;

[0481] (424) 1-(5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-ol;

[0482] (425) ((1r,4r)-4-(((5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)methyl)cyclohexyl)methanol;

[0483] (426) N-(5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0484] (427) (1s,4s)-4-((5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexan-1-ol;

[0485] (428) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridin-3-yl)ethynyl)tetrahydrothiophene 1,1-dioxide;

[0486] (429) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-hydroxy-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)tetrahydrothiophene 1,1-dioxide;

[0487] (430) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0488] (431) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol;

[0489] (432) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol;

[0490] (433) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0491] (434) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0492] (435) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol;

[0493] (436) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0494] (437) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)tetrahydrothiophene 1,1-dioxide;

[0495] (438) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0496] (439) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0497] (440) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0498] (441) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone;

[0499] (442) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-hydroxy-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone;

[0500] (443) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-((((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)amino)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone;

[0501] (444) (R)-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone;

[0502] (445) (S)-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone;

[0503] (446) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone;

[0504] (447) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3-methylpiperidin-3-ol;

[0505] (448) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3-methylpiperidin-3-ol; and

[0506] (449) (1-(2-((2-(4-(cyclopropylsulfonyl)piperazin-1-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol.

[0507] Further representative compounds of formula (I) are listed below.

[0508] (1) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-methylpiperazin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0509] (4) (R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)butan-1-ol;

[0510] (5) (S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-2-methylbutan-2-ol;

[0511] (6) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0512] (7) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-one;

[0513] (8) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoropiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0514] (9) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol;

[0515] (10) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0516] (11) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)propan-2-ol;

[0517] (12) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0518] (13) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0519] (14) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol;

[0520] (15) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-methoxypiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0521] (17) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0522] (18) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0523] (19) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0524] (20) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -isopropylpyridine-2,4-diamine;

[0525] (21) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-(pyridin-3-ylethynyl)pyridine-2,4-diamine;

[0526] (23) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -isopropylpyridine-2,4-diamine;

[0527] (26) N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0528] (27) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0529] (28) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0530] (29) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol;

[0531] (30) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol;

[0532] (31) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol;

[0533] (32) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol;

[0534] (33) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol;

[0535] (34) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol;

[0536] (35) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol;

[0537] (39) 3-((2-((2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl)amino)-5-(2-(1-methylpyrazol-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propan-1-ol;

[0538] (40) 3-((2-((2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl)amino)-5-(2-(1-(2-fluoroethyl)pyrazol-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propan-1-ol;

[0539] (41) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0540] (42) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0541] (43) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0542] (44) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0543] (45) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0544] (47) (1-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0545] (48) (1-(5-((1-(cyclopropylmethyl)-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0546] (49) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0547] (53) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0548] (58) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0549] (59) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0550] (60) N-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine;

[0551] (68) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3,3-difluoropiperidin-4-ol;

[0552] (73) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0553] (75) (1R,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0554] (81) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol;

[0555] (82) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0556] (83) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol;

[0557] (84) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0558] (85) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0559] (86) 1-(5-((5-cyclopropyl-1-methyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-ol;

[0560] (87) 2-(1-(5-((5-cyclopropyl-1-methyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0561] (88) (1s,4s)-4-((5-((5-cyclopropyl-1-methyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexan-1-ol;

[0562] (90) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol;

[0563] (91) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0564] (94) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0565] (95) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0566] (96) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0567] (99) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0568] (100) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol;

[0569] (101) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0570] (106) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0571] (107) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0572] (110) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0573] (112) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-fluoropiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0574] (113) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-methoxypiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0575] (114) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one;

[0576] (116) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0577] (117) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0578] (118) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol;

[0579] (119) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0580] (120) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0581] (121) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0582] (122) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol;

[0583] (123) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0584] (126) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2,2-difluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0585] (129) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0586] (136) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidin-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0587] (147) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0588] (148) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0589] (149) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0590] (150) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0591] (152) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0592] (157) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0593] (164) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0594] (169) (1S,3R)-3-((5-((3-aminophenyl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexan-1-ol;

[0595] (177) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)cyclopentan-1-ol;

[0596] (178) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0597] (179) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0598] (180) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylpyrrolidin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0599] (182) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylpiperidin-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0600] (185) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyridin-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0601] (186) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-(morpholinomethyl)pyridin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0602] (187) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-(morpholinomethyl)pyridin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0603] (189) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(morpholinomethyl)thiazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0604] (191) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)thiophen-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0605] (192) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(morpholinomethyl)thiazol-5-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0606] (193) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidin-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0607] (197) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0608] (207) N-(5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(isopropylamino)pyridin-3-yl)pent-4-yn-1-yl)morpholine-4-carboxamide;

[0609] (210) 7-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(isopropylamino)pyridin-3-yl)-1-morpholinohept-6-yn-1-one;

[0610] (211) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methylthiazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0611] (216) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-imidazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0612] (217) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(thiophen-3-ylethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0613] (218) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0614] (219) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-morpholinoethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0615] (220) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol;

[0616] (231) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0617] (232) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-morpholinoethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0618] (238) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((2-methylthiazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0619] (241) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-3-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0620] (242) (1-(5-((1-((1,4-dioxan-2-yl)methyl)-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0621] (243) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydrofuran-3-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0622] (244) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0623] (245) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(oxetan-3-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0624] (248) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-((3,3-difluoroazetidin-1-yl)methyl)-1-(2,2-difluoroethyl)-1H-pyrrol-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0625] (253) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0626] (254) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((dimethylamino)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0627] (255) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-((dimethylamino)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0628] (258) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-4-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0629] (260) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-3-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0630] (261) (3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(morpholino)methanone;

[0631] (262) 4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)-N,N-dimethylbenzamide;

[0632] (263) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(morpholino)methanone;

[0633] (264) 6-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)-N,N-dimethylpicolinamide;

[0634] (266) 2-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)cyclobutyl)propan-2-ol;

[0635] (274) 4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)but-3-yn-1-ol;

[0636] (276) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(4-fluorobut-1-yn-1-yl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0637] (277) (1-(5-(but-3-en-1-yn-1-yl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0638] (278) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-((dimethylamino)methyl)pyridin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0639] (279) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-((4-methylpiperazin-1-yl)methyl)pyridin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0640] (280) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-3-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol;

[0641] (283) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-(pyridin-3-ylethynyl)-4-(1-oxa-7-azaspiro[3.5]nonan-7-yl)pyridin-2-yl)pyrimidin-4-amine;

[0642] (284) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)-2-methylpent-4-yn-2-ol;

[0643] (287) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)pent-4-yn-2-ol;

[0644] (288) N-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)prop-2-yn-1-yl)-2,2,2-trifluoroacetamide;

[0645] (294) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine formate;

[0646] (305) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0647] (306) (1R,3S)-3-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclopentan-1-ol;

[0648] (308) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0649] (309) 5-((1-(cyclopropylmethyl)-1H-pyrazol-4-yl)ethynyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine;

[0650] (310) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine;

[0651] (311) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine;

[0652] (312) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0653] (313) 5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine;

[0654] (314) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0655] (324) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0656] (327) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0657] (339) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0658] (340) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0659] (342) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0660] (347) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0661] (348) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0662] (352) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(oxetan-3-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0663] (353) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(oxetan-3-ylethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0664] (358) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0665] (360) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0666] (368) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol;

[0667] (374) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0668] (376) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0669] (378) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0670] (379) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0671] (396) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0672] (397) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0673] (399) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0674] (401) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0675] (402) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0676] (404) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol;

[0677] (407) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-methylcyclopropyl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0678] (408) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one;

[0679] (422) ((1s,4s)-4-((5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexyl)methanol;

[0680] (427) (1s,4s)-4-((5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexan-1-ol;

[0681] (430) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0682] (433) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0683] (442) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-hydroxy-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone;

[0684] (446) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone; and

[0685] (447) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3-methylpiperidin-3-ol.

[0686] More preferred representative compounds of formula (I) are listed below.

[0687] (6) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0688] (10) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0689] (12) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0690] (13) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0691] (18) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0692] (19) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine;

[0693] (20) N2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -isopropylpyridine-2,4-diamine;

[0694] (27) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0695] (30) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol;

[0696] (35) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol;

[0697] (39) 3-((2-((2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl)amino)-5-(2-(1-methylpyrazol-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propan-1-ol;

[0698] (41) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0699] (43) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0700] (47) (1-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0701] (49) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0702] (73) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol;

[0703] (82) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol;

[0704] (85) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0705] (101) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0706] (126) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2,2-difluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0707] (129) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine;

[0708] (157) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol;

[0709] (260) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-3-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0710] (305) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0711] (324) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0712] (327) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol;

[0713] (360) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; and

[0714] (379) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol.

[0715] Even more preferred representative compounds of formula (I) are listed below.

[0716] (6) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0717] (10) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0718] (12) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0719] (13) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0720] (35) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol;

[0721] (47) (1-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0722] (49) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0723] (101) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol;

[0724] (126) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2,2-difluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; and

[0725] (129) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine.

[0726] Single stereochemical isomers, enantiomers, diastereomers, and pharmaceutically acceptable salts of the above-exemplified compounds are also within the scope of the present invention. Pharmaceutically acceptable salts may be derived, for example, from suitable inorganic and organic acids and bases.

[0727] Acid addition salts can be prepared by reacting the purified compound, if possible in free base form, with a suitable organic or inorganic acid and isolating the salt formed. Examples of pharmaceutically acceptable acid addition salts include, but are not limited to, salts of amino groups formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid.

[0728] Base addition salts can be prepared by reacting the purified compound in its acid form with a suitable organic or inorganic base and isolating the salt formed. Such salts include alkali metal (e.g., sodium, lithium, and potassium), alkaline earth metal (e.g., magnesium and calcium), ammonium, and N + (C 1-4 Examples include, but are not limited to, salts of alkyl).

[0729] Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, glycolate, gluconate, glycolate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxybenzoates, and the like. Examples of suitable salts include ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, palmate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, and valerate.

[0730] The compounds of the present invention can be synthesized by methods known in the art or by methods illustrated in Examples 1-449 below.

[0731] Pharmaceutical compositions, methods and uses In one embodiment, the present invention relates to a method of treating a protein kinase-mediated disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt, diastereomer, enantiomer, racemate, tautomer, prodrug, hydrate, or solvate thereof. In certain embodiments, the protein kinase-mediated disease is cancer or an immune disease.

[0732] As used herein, the term "cancer" refers to the abnormal proliferation of cells that tend to grow uncontrolled and sometimes metastasize.Cancer types include but are not limited to solid tumors such as bladder cancer, colorectal cancer, brain cancer, breast cancer, ovarian cancer, endometrial cancer, uterine cancer, heart cancer, kidney cancer, lung cancer, liver cancer, stomach cancer, lymphoma, pancreatic cancer, head and neck cancer or other endocrine organ cancer (thyroid cancer), prostate cancer, skin cancer (melanoma) or blood tumor (such as leukemia).In another embodiment, cancer is non-small cell lung cancer (NSCLC).

[0733] In one embodiment, the methods disclosed herein relate to the treatment of cancer caused by at least one mutation in EGFR.

[0734] In one embodiment, the method of treating cancer is particularly useful for patients who are resistant to kinase inhibitors other than the compounds of the invention, or pharmaceutically acceptable salts, solvates, esters, or prodrugs thereof. In another embodiment, the kinase inhibitor is a mutant EGFR inhibitor.

[0735] The present invention also relates to a method for selectively inhibiting at least one mutant form of EGFR relative to wild-type EGFR in a biological sample or in a patient, comprising contacting the biological sample with a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt thereof, or administering to the patient a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt thereof.

[0736] In one embodiment, the at least one variant is at least one single variant selected from Table 1 shown below.

[0737] In one embodiment, the at least one mutant is at least one double mutant selected from Table 1 below.

[0738] In one embodiment, the at least one mutant is at least one triple mutant selected from Table 1 below.

[0739] [Table 1]

[0740] The present invention also relates to methods of treatment and uses that include administering the compounds of the present invention, or pharmaceutically acceptable salts, diastereomers, enantiomers, racemates, tautomers, prodrugs, hydrates or solvates thereof, alone or in combination with other therapeutic or palliative agents.

[0741] A further embodiment of the present invention relates to a compound of the present invention for use as a pharmaceutical, in particular for use in the treatment of diseases in which inhibition of mutated EGFR protein (e.g., those listed in Table 1) activity can induce benefit, such as cancer. A further embodiment of the present invention relates to the use of a compound of the present invention, or a pharmaceutically acceptable salt, diastereomer, enantiomer, racemate, tautomer, prodrug, hydrate or solvate thereof, for the manufacture of a medicament having inhibitory activity against EGFR for the treatment of EGFR-mediated diseases and / or conditions, in particular the diseases and / or conditions listed above.

[0742] The term "therapeutically effective amount" refers to the amount of compound administered that will relieve to some extent one or more symptoms of the disorder being treated. In the context of treating cancer, a therapeutically effective amount refers to an amount that has the effect of reducing tumor size, inhibiting (i.e., slowing or stopping) tumor metastasis, inhibiting (i.e., slowing or stopping) tumor growth or tumor invasion, and / or alleviating to some extent one or more signs or symptoms associated with cancer.

[0743] A therapeutically effective amount can be readily determined by an attending diagnostician skilled in the art using conventional techniques and observing results obtained under similar circumstances. In determining a therapeutically effective amount, or dose, the attending physician will consider many factors, including, but not limited to: the species of mammal; its size, age, and general health; the specific disease involved; the extent or severity of the disease involved; the response of the individual patient; the specific compound administered; the method of administration; the bioavailability characteristics of the administered formulation; the selected dosage regimen; the use of concomitant medications; and other relevant circumstances.

[0744] As used herein, unless otherwise specified, the term "treating" means reversing, alleviating, inhibiting the progression of, or preventing the disorder or condition to which such term applies, or one or more symptoms of such disorder or condition. The term "treatment" also refers to the act of treating, as "treating" is defined immediately above. The term "treating" also includes adjuvant treatment of a mammal.

[0745] As used herein, the term "subject" or "patient" includes mammals and non-mammals. Examples of mammals include, but are not limited to, humans, chimpanzees, apes, cows, horses, sheep, goats, pigs, rabbits, dogs, cats, rats, mice, guinea pigs, etc. Examples of non-mammals include, but are not limited to, birds, fish, etc.

[0746] As used herein, the term "biological sample" includes cells, tissues, and fluids obtained (isolated) from mammals, such as humans (e.g., patients with cancer), or the non-mammals exemplified above, and cultures thereof.

[0747] Administration of the compounds of the present invention can be achieved by any method that allows delivery of the compound to the site of action, including oral routes, intraduodenal routes, parenteral injection (including intravenous, subcutaneous, intramuscular, intravascular or infusion), topical and rectal administration.

[0748] Also provided herein in another aspect are pharmaceutical compositions comprising a compound of Formula (I) as an active ingredient, a pharmaceutically acceptable salt, diastereomer, enantiomer, racemate, tautomer, prodrug, hydrate, or solvate thereof, and a pharmaceutically acceptable excipient. In one embodiment, the pharmaceutical composition is for treating a protein kinase-mediated disease. In another embodiment, the pharmaceutical composition is for selectively inhibiting at least one mutant form of EGFR compared to wild-type EGFR.

[0749] The compound of the present invention can be administered orally.Oral administration can involve swallowing, so that compound enters the gastrointestinal tract, or can also use buccal or sublingual administration, so that compound enters the bloodstream directly from the mouth.The formulation suitable for oral administration includes solid formulations such as tablets, capsules containing particles, liquids, or powders, lozenges (including liquid-filled), chewable tablets, multi-particles and nanoparticles, gels, solid solutions, liposomes, films (including mucoadhesives), ovules, sprays and liquid formulations.

[0750] Liquid preparations include suspension, solution, syrup and elixir.Such preparations can be used as filler in soft capsule or hard capsule, and can typically contain carrier such as water, ethanol, polyethylene glycol, propylene glycol, methylcellulose or suitable oil, and one or more emulsifiers and / or suspending agents.Liquid preparations can also be produced by reconstituting solid.

[0751] Examples of carriers, additives, and diluents that can be included in the composition include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, mineral oil, etc. When formulating, commonly used diluents and additives such as fillers, stabilizers, binders, disintegrants, surfactants, etc. can be used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations can be prepared by mixing the compound of the present invention with at least one additive, such as starch, crystalline cellulose, sucrose, lactose, low-substituted hydroxypropyl cellulose, hypromellose, etc. In addition to simple additives, lubricants such as magnesium stearate and talc can also be used. Oral liquid preparations include suspensions, oral solutions, emulsions, syrups, etc. In addition to commonly used simple diluents such as water and liquid paraffin, they may contain various additives such as humectants, sweeteners, flavorings, and preservatives. Parenteral preparations include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solutions or suspensions may contain propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases include witepsol, macrogol, Tween 61, cocoa butter, lauric butter, and glycerogelatin. To prepare a preparation for parenteral administration, the compound of formula I or a pharmaceutically acceptable salt thereof is sterilized and mixed in water and / or contains auxiliary agents such as preservatives, stabilizers, hydrating powders or emulsifiers, salts for adjusting osmotic pressure and / or buffers, and other therapeutically useful substances to prepare a solution or suspension, which is then prepared in the form of a unit dose in an ampoule or vial.

[0752] General reaction scheme and synthetic route overview The present invention includes within its scope a method for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof according to the following Scheme 1: [ka] In the reaction scheme, R1, R2, R3, and R4 are the same as above. X is a halogen. M is hydrogen, B(OH)2, or BPin.

[0753] Specifically, the compound of formula (I) or a pharmaceutically acceptable salt thereof can be prepared using a process comprising the steps of: reacting a compound of formula (II) with R2-M to obtain a compound of formula (IV), reacting the compound of formula (IV) with a compound of formula (III) to obtain a compound of formula (VI), and reacting the compound of formula (VI) with a compound of formula (VII) to obtain a compound of formula (I).

[0754] In the process of Reaction Scheme 1, compounds of formula (II), (III), and (VII) and R2-M are commercially available. The reaction of compound of formula (II) with R2-M may be carried out in the presence of a base such as sodium hydride, potassium carbonate, cesium carbonate, potassium hydroxide, TEA, or DIPEA. The reaction may also be carried out in an organic solvent such as anhydrous THF, DMF, or DMA at room temperature or under heating, for example, at a temperature of 40 to 140°C. When M is B(OH)2 or BPin, the reaction may be carried out in the presence of a base such as sodium carbonate or potassium carbonate and Pd(dppf)Cl. 2、 The reaction may be carried out in the presence of a ligand-bound palladium catalyst such as Pd(PPh3)4. Furthermore, when M is B(OH)2 or BPin, the reaction may be carried out in an anhydrous organic solvent (e.g., THF, 1,4-dioxane, etc.) under heating, for example, at a temperature of 40 to 120°C.

[0755] The Sonogashira reaction couples a compound of formula (IV) with a compound of formula (III) to give a compound of formula (VI). The reaction of compounds of formula (IV) and (III) may be carried out in the presence of a base such as TEA or diethylamine, and a palladium complex and a copper(I) halide catalyst, such as PdCl(PPh), Pd(PPh), or copper(I) iodide. The reaction may be carried out in an organic solvent such as TEA or DMF at room temperature or under heating, e.g., at 40 to 100°C.

[0756] Alternatively, a compound of formula (VI) may be prepared by reacting a compound of formula (II) with a compound of formula (III) to give a compound of formula (V), and reacting the compound of formula (V) with R2-M.

[0757] The Sonogashira reaction couples a compound of formula (II) with a compound of formula (III) to give a compound of formula (V). The reaction of compounds of formula (II) and (III) may be carried out in the presence of a base such as TEA or diethylamine, and a palladium complex and a copper(I) halide catalyst, such as PdCl(PPh), Pd(PPh), or copper(I) iodide. The reaction may be carried out in an organic solvent such as TEA or DMF at room temperature or under heating, e.g., 40-100°C.

[0758] The reaction of the compound of formula (V) with R2-M may be carried out in the presence of a base such as sodium hydride, potassium carbonate, cesium carbonate, potassium hydroxide, TEA, or DIPEA. Furthermore, the reaction may be carried out in an organic solvent such as anhydrous THF, DMF, or DMA at room temperature or under heating, for example, at a temperature of 40 to 140°C. When M is B(OH)2 or BPin, the reaction may be carried out in the presence of a base such as sodium carbonate or potassium carbonate and Pd(dppf)Cl. 2、The reaction may be carried out in the presence of a ligand-bound palladium catalyst such as Pd(PPh3)4. Furthermore, when M is B(OH)2 or BPin, the reaction may be carried out in an anhydrous organic solvent (e.g., THF, 1,4-dioxane, etc.) under heating, for example, at a temperature of 40 to 120°C.

[0759] A compound of formula (VI) is coupled with a compound of formula (VII) via the Buchwald-Hartwig reaction to obtain a compound of formula (I). The reaction of compounds of formula (VI) and (VII) may be carried out in the presence of a base such as sodium carbonate, potassium carbonate, or cesium carbonate. The reaction may also be carried out in the presence of a palladium catalyst such as Pd(OAc)2, Pd2(dba)3, Pd(PPh3)4, Pd(dppf)Cl2, or BrettPhos Pd G1 methyl t-butyl ether adduct, and a ligand such as BINAP, SPhos, XPhos, Xantphos, or BrettPhos. The reaction may also be carried out in an anhydrous organic solvent such as 1,4-dioxane or toluene, under heating, for example, at a temperature of 80 to 120°C.

[0760] According to another aspect of the present invention, the compound of formula (I) or a pharmaceutically acceptable salt thereof may be prepared according to the following Reaction Scheme 2: [ka] In the reaction formula, R1 is A-(R 1A ) m and P is a trialkylsilyl protecting group such as TMS, TES, TBS, TIPS, TBDMS, etc. 1A , R2, R3, R4, and m are the same as above. X is a halogen.

[0761] Specifically, the compound of formula (I) or a pharmaceutically acceptable salt thereof can be prepared using a process comprising the steps of: removing a protecting group from a compound of formula (Ia) to obtain a compound of formula (Ib), and reacting the compound of formula (Ib) with R1-X to obtain a compound of formula (I).

[0762] The trialkylsilyl protecting group of the compound of formula (Ia) may be removed in the presence of a base such as potassium carbonate or a fluorinating agent such as TBAF, and the reaction may be carried out in an anhydrous organic solvent such as THF, DCM, or MeOH at room temperature or with heating.

[0763] The compound of formula (Ib) is coupled with R1-X via the Sonogashira reaction to give the compound of formula (I). The reaction of the compound of formula (Ib) with R1-X may be carried out in the presence of a base such as TEA or diethylamine, and a palladium complex and a copper(I) halide catalyst such as PdCl2(PPh3)2, Pd(PPh3)4, or copper(I) iodide. The reaction may also be carried out in an organic solvent such as TEA or DMF at room temperature or under heating, e.g., at 40 to 100°C.

[0764] Alternatively, the compound of formula (VII) can be obtained by reacting the compound of formula (VIII) with a compound of formula R3-M according to the following reaction scheme 3: [ka] In the reaction scheme, R3 and R4 are the same as above, X is a halogen, and M is hydrogen, B(OH)2, or BPin.

[0765] The reaction of the compound of formula (VIII) with R3-M may be carried out in the presence of a base such as sodium hydride, potassium carbonate, cesium carbonate, potassium hydroxide, TEA, or DIPEA. The reaction may also be carried out in an organic solvent such as anhydrous THF, DMF, or DMA at room temperature or under heating, for example, at a temperature of 40 to 140°C. When M is B(OH)2 or BPin, the reaction may be carried out in the presence of a base such as sodium carbonate or potassium carbonate and PdCl2(PPh3)2, Pd(dppf)Cl 2、The reaction may be carried out in the presence of a ligand-bound palladium catalyst such as Pd(PPh3)4. Furthermore, when M is B(OH)2 or BPin, the reaction may be carried out in an anhydrous organic solvent (e.g., THF, 1,4-dioxane, acetonitrile, etc.) under heating, for example, at a temperature of 40 to 120°C.

[0766] Example The present invention is further illustrated by the following examples, which illustrate the preparation of compounds of formula (I) according to the present invention. The examples are for illustrative purposes only and are not intended to, and should not be construed as, limiting the present invention in any way. Those skilled in the art will understand that variations and modifications can be made without changing the scope of the present invention.

[0767] The compounds prepared in the following examples were analyzed as follows. Nuclear magnetic resonance (NMR) spectroscopy was performed using a Bruker 400 MHz spectrometer and an Agilent 600 MHz spectrometer, and chemical shifts were reported in ppm. The molecular weights shown were measured using an Agilent 1260 Infinity Series liquid chromatography / mass selective detector (MSD) equipped with an electrostatic spray interface (using a single quadrupole, and the m / z values ​​shown are those in ESI+ (ESI-MS (cation)) represented by the [M + H] + peak). Column chromatography was performed on silica gel (Merck, 70-230 meS) (WC Still, J. Org. Chem., 43, 2923, 1978). The starting materials in each example were known compounds, synthesized according to literature sources, or obtained commercially from suppliers such as Sigma-Aldrich. The abbreviations used in the following examples are as follows:

[0768] [Table 2]

[0769] Preparation Example 1: N-(sec-butyl)-2-chloro-5-iodopyridin-4-amine A suspension of 2-chloro-5-iodo-pyridin-4-amine (1.00 g, 3.930 mmol), 2-iodobutane (0.54 mL, 4.716 mmol), and CsCO (2.56 g, 7.680 mmol) in 1,4-dioxane (10 mL) was stirred at 80 °C overnight. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO, and concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-10%) to give N-(sec-butyl)-2-chloro-5-iodopyridin-4-amine (134 mg) as a pale yellow oil. MS (ESI) m / z = 311.0 (M+H). +

[0770] Preparation Example 2: 1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-ol A suspension of 2,4-dichloro-5-iodopyridine (400 mg, 1.46 mmol), 4-hydroxypiperidine (221 mg, 2.191 mmol), and DIPEA (0.51 mL, 2.921 mmol) in DMA (7 mL) was stirred at 100 °C overnight. After cooling, the reaction mixture was diluted with EA, washed with water, dried over MgSO4, and concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-15%) to give 1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-ol (468 mg) as a yellow solid. MS (ESI) m / z = 339.0 (M+H) +

[0771] Preparation 3: (1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)methanol The title compound (458 mg) was prepared as a solid in the same manner as in Preparation 2, except that 4-piperidinemethanol (252 mg, 2.191 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 353.0 (M+H) +

[0772] Production Example 4: (R)-1-(2-chloro-5-iodopyridin-4-yl)pyrrolidin-3-ol The title compound (245.1 mg) was prepared as a solid in the same manner as in Preparation 2, except that (R)-pyrrolidin-3-ol HCl (270 mg, 2.191 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 325.0 (M+H) +

[0773] Preparation 5: (1-(2-chloro-5-iodopyridin-4-yl)pyrrolidin-3-yl)methanol The title compound (413 mg) was prepared as a solid in the same manner as in Preparation 2, except that pyrrolidin-3-ylmethanol (221 mg, 2.191 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 339.0 (M+H) +

[0774] Preparation 6: 2-(1-(2-chloro-5-iodopyridin-4-yl)azetidin-3-yl)propan-2-ol The title compound (261 mg) was prepared as a solid in the same manner as in Preparation 2, except that 2-(azetidin-3-yl)propan-2-ol HCl (215 mg, 1.424 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 353.0 (M+H) +

[0775] Preparation Example 7: 2-((2-chloro-5-iodopyridin-4-yl)(methyl)amino)ethan-1-ol The title compound (569 mg) was prepared as a solid in the same manner as in Preparation 2, except that 2-(methylamino)ethanol (205 mg, 2.738 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 313.0 (M+H) +

[0776] Preparation 8: 3-((2-chloro-5-iodopyridin-4-yl)amino)-2,2-dimethylpropan-1-ol The title compound (319 mg) was prepared as a solid in the same manner as in Preparation 2, except that 3-amino-2,2-dimethyl-1-propanol (225 mg, 2.191 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 341.0 (M+H) +

[0777] Production Example 9: (1s,4s)-4-((2-chloro-5-iodopyridin-4-yl)amino)cyclohexan-1-ol The title compound (836 mg) was prepared as a solid in the same manner as in Preparation 2, except that (1s,4s)-4-aminocyclohexan-1-ol HCl (1.06 g, 6.992 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 353.0 (M+H) +

[0778] Preparation 10: (1S,3S)-3-((2-chloro-5-iodopyridin-4-yl)amino)cyclohexan-1-ol The title compound (790 mg) was prepared as a solid in the same manner as in Preparation 2, except that (1S,3S)-3-aminocyclohexan-1-ol HCl (1.06 g, 6.992 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 353.0 (M+H) +

[0779] Production Example 11: (1S,3R)-3-((2-chloro-5-iodopyridin-4-yl)amino)cyclohexan-1-ol The title compound (953 mg) was prepared as a solid in the same manner as in Preparation 2, except that (1S,3R)-3-aminocyclohexan-1-ol (805 mg, 6.992 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 353.0 (M+H) +

[0780] Preparation 12: (1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperidin-4-yl)methanol The title compound (2.3 g) was prepared as a solid in the same manner as in Preparation 2, except that (4-methylpiperidin-4-yl)methanol (1.30 g, 10.100 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 366.9 (M+H) +

[0781] Preparation Example 13: 2-chloro-N-(4-((dimethylamino)methyl)benzyl)-5-iodopyridin-4-amine The title compound (756 mg) was prepared as a solid in the same manner as in Preparation 2, except that 1-(4-(aminomethyl)phenyl)-N,N-dimethylmethanamine (539 mg, 3.286 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 402.0 (M+H) +

[0782] Preparation 14: 2-chloro-5-iodo-4-isopropoxypyridine To a suspension of 2,4-dichloro-5-iodo-pyridine (500 mg, 1.826 mmol) and NaH (109 mg, 2.738 mmol) in THF (10 mL) was added 2-propanol (131 mg, 2.191 mmol). The reaction mixture was stirred at room temperature for 2 hours, quenched with water, extracted with EA, dried over MgSO4, and concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-20%) to give 2-chloro-5-iodo-4-isopropoxypyridine (270 mg) as an off-white solid. MS (ESI) m / z = 298.0 (M+H). +

[0783] Preparation Example 15: 4-(sec-butoxy)-2-chloro-5-iodopyridine The title compound (250 mg) was prepared as a solid in the same manner as in Preparation 14, except that 2-butanol (162 mg, 2.191 mmol) was used instead of 2-propanol. MS (ESI) m / z = 312.0 (M+H) +

[0784] Preparation 16: 1-((1r,4r)-4-(((2-chloro-5-iodopyridin-4-yl)oxy)methyl)cyclohexyl)-N,N-dimethylmethanamine Step 1: tert-butyl (((1r,4r)-4-(((2-chloro-5-iodopyridin-4-yl)oxy)methyl)cyclohexyl)methyl)carbamate The title compound (1.46 g) was prepared as a solid in the same manner as in Preparation 14, except that tert-butyl (trans-4-hydroxymethylcyclohexylmethyl)carbamate (3.20 g, 13.144 mmol) was used instead of 2-propanol. MS (ESI) m / z = 481.0 (M+H) + Step 2: 1-((1r,4r)-4-(((2-chloro-5-iodopyridin-4-yl)oxy)methyl)cyclohexyl)-N,N-dimethylmethanamine A solution of tert-butyl (((1r,4r)-4-(((2-chloro-5-iodopyridin-4-yl)oxy)methyl)cyclohexyl)methyl)carbamate (1.00 g, 2.080 mmol) prepared in Step 1 in 20% TFA in DCM (10 mL) was stirred at room temperature overnight. The reaction mixture was quenched with saturated NaHCO3 solution, extracted with DCM, dried over MgSO4, and concentrated. The residue was dissolved in MeOH (10 mL), and then formaldehyde (4.65 mL, 62.400 mmol) and NaBH(OAc)3 (1.32 g, 6.240 mmol) were added. The reaction mixture was stirred at 60 °C overnight, quenched with saturated NaHCO3 solution, extracted with DCM, dried over MgSO4, and concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-10%) to give 1-((1r,4r)-4-(((2-chloro-5-iodopyridin-4-yl)oxy)methyl)cyclohexyl)-N,N-dimethylmethanamine (549 mg) as an off-white solid. MS (ESI) m / z = 409.0 (M+H) +

[0785] Preparation Example 17: tert-butyl (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)carbamate Step 1: tert-Butyl (1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)carbamate The title compound (1.65 g) was prepared as a solid in the same manner as in Preparation 2, except that 4-(tert-butoxycarbonylamino)piperidine (1.42 g, 7.120 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 438.0 (M+H) + Step 2: tert-butyl (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)carbamate A mixture of tert-butyl (1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)carbamate (1.5 g, 3.427 mmol), 4-ethynyl-1-methylpyrazole (436 mg, 4.112 mmol), PdCl(PPh) (120 mg, 0.171 mmol), and CuI (130.6 mg, 0.685 mmol) was purged with nitrogen gas for 10 min. DMF (30 mL) and TEA (0.96 mL, 6.854 mmol) were added, and the reaction mixture was stirred at 50 °C for 1 h. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO, and concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-10%) to give tert-butyl (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)carbamate (1.05 g) as a yellow solid. MS (ESI) m / z = 416.2 (M+H) + Step 3: tert-butyl (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)carbamate A suspension of 2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-amine (428 mg, 1.615 mmol), tert-butyl (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)carbamate (590 mg, 1.468 mmol) prepared in Step 2, CsCO (956 mg, 2.936 mmol), XPhos (139 mg, 0.294 mmol), and tris(dibenzylideneacetone)dipalladium(0) (134 mg, 0.147 mmol) in 1,4-dioxane (9 mL) was stirred at 90 °C for 4 h. The reaction mixture was cooled, filtered through Celite, and concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-100%) to give tert-butyl (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)carbamate (372 mg) as a yellow solid. MS (ESI) m / z = 645.3 (M+H) +

[0786] Preparation 18: 2-chloro-4-fluoro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine A mixture of 2-chloro-4-fluoro-5-iodopyridine (3.50 g, 13.600 mmol), 4-ethynyl-1-methylpyrazole (1.59 g, 14.956 mmol), PdCl(PPh) (477 mg, 0.680 mmol), and CuI (518 mg, 2.719 mmol) was purged with nitrogen gas for 10 min. DMF (40 mL) and TEA (3.79 mL, 27.192 mmol) were added, and the reaction mixture was stirred at 50 °C for 1 h. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO, and concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-40%) to give 2-chloro-4-fluoro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine (2.00 g) as an off-white solid. 1 H-NMR (CDCl3, 600 MHz) δ 8.49 (d, 1H), 7.68 (s, 1H), 7.62 (s, 1H), 7.13 (d, 1H), 3.93 (s, 3H); MS (ESI) m / z = 236.0 (M+H) +

[0787] Preparation 19: 2-chloro-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)-4-fluoropyridine The title compound (669.6 mg) was prepared as a solid in the same manner as in Preparation 18, except that 1-(2,2-difluorocyclopropyl)-4-ethynylpyrazole (517 mg, 3.077 mmol) was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 298.0 (M+H) +

[0788] Preparation 20: 2-chloro-5-((5-cyclopropyl-1-methyl-1H-pyrazol-4-yl)ethynyl)-4-fluoropyridine The title compound (545 mg) was prepared as a solid in the same manner as in Preparation 18, except that 5-cyclopropyl-4-ethynyl-1-methylpyrazole (449 mg, 3.077 mmol) was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 276.0 (M+H) +

[0789] Preparation 21: 2-chloro-4-fluoro-5-(2-(1-methyl-3-(trifluoromethyl)pyrazol-4-yl)ethynyl)pyridine The title compound (651 mg) was prepared as a solid in the same manner as in Preparation 18, except that 4-ethynyl-1-methyl-3-(trifluoromethyl)pyrazole (535 mg, 3.077 mmol) was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 304.0 (M+H) +

[0790] Preparation 22: 2-chloro-4-fluoro-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridine The title compound (838 mg) was prepared as a solid in the same manner as in Preparation 18, except that 4-ethynyl-1-tetrahydropyran-4-ylpyrazole (1.13 g, 6.410 mmol) was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 306.1 (M+H) +

[0791] Preparation 23: 2-chloro-4-fluoro-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridine The title compound (460 mg) was prepared as a solid in the same manner as in Preparation 18, except that 4-ethynyl-1-(trifluoromethyl)pyrazole (1.03 g, 6.410 mmol) was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 290.0 (M+H) +

[0792] Preparation 24: 2-chloro-4-fluoro-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridine The title compound (950 mg) was prepared as a solid in the same manner as in Preparation 18, except that 3-ethynyl-1-methylpyrazole (680 mg, 6.410 mmol) was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 236.0 (M+H) +

[0793] Preparation 25: 1-(4-(4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one Step 1: tert-butyl 4-(4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate The title compound (3.20 g) was prepared as a solid in the same manner as in Preparation 18, except that tert-butyl 4-(4-ethynylpyrazol-1-yl)piperidine-1-carboxylate (3.53 g, 12.819 mmol) was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 349.0 (M+H) + Step 2: 1-(4-(4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one tert-Butyl 4-(4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (1.00 g, 2.470 mmol) prepared in Step 1 was dissolved in 4.0 M HCl in 1,4-dioxane (10 mL) and stirred at 60 °C overnight. The reaction mixture was concentrated, and the residue was dissolved in DCM (10 mL). Acetyl chloride (1.1 mL, 7.410 mmol) and TEA (2.07 mL, 14.820 mmol) were added, and the reaction mixture was stirred at room temperature for 3 hours. The mixture was washed with water, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-100%) to give 1-(4-(4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one (820 mg) as a yellow solid. MS (ESI) m / z = 347.0 (M+H) +

[0794] Preparation 26: 2-(4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)-N,N-dimethylethan-1-amine Step 1: 2-(4-ethynyl-1H-pyrazol-1-yl)-N,N-dimethylethan-1-amine A suspension of 4-ethynyl-1H-pyrazole (400 mg, 4.343 mmol), 2-iodo-N,N-dimethylethan-1-amine HCl (1.33 g, 5.646 mmol), and CsCO (4.25 g, 13.030 mmol) in DMA (40 mL) was stirred at 80 °C overnight. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO, and concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-15%) to give 2-(4-ethynyl-1H-pyrazol-1-yl)-N,N-dimethylethan-1-amine (545 mg) as a yellow oil. MS (ESI) m / z = 164.1 (M+H). + Step 2: 2-(4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)-N,N-dimethylethan-1-amine The title compound (544 mg) was prepared as an oil in the same manner as in Preparation 18, except that 2-(4-ethynyl-1H-pyrazol-1-yl)-N,N-dimethylethan-1-amine (532 mg, 3.263 mmol) prepared in Step 1 was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 293.0 (M+H) +

[0795] Preparation 27: 3-(4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)-N,N-dimethylpropan-1-amine Step 1: 3-(4-ethynyl-1H-pyrazol-1-yl)-N,N-dimethylpropan-1-amine The title compound (583 mg) was prepared as an oil in the same manner as in Step 1 of Preparation 26, except that 3-chloro-N,N-dimethylpropan-1-amine HCl (892 mg, 5.646 mmol) was used instead of 2-iodo-N,N-dimethylethan-1-amine HCl. MS (ESI) m / z = 178.2 (M+H) + Step 2: 3-(4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)-N,N-dimethylpropan-1-amine The title compound (577 mg) was prepared as a solid in the same manner as in Preparation 18, except that 3-(4-ethynyl-1H-pyrazol-1-yl)-N,N-dimethylpropan-1-amine (578 mg, 3.263 mmol) prepared in Step 1 was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 307.0 (M+H) +

[0796] Preparation 28: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)piperidin-4-one Step 1: 1-(2-chloro-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)piperidin-4-one A suspension of 2-chloro-4-fluoro-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridine (300 mg, 1.273 mmol) prepared in Preparation 24, piperidin-4-one HCl hydrate (293 mg, 1.91 mmol), and DIPEA (0.67 mL, 3.819 mmol) in DMA (7 mL) was stirred at 50° C. for 3 hours. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO4, and concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-5%) to give 1-(2-chloro-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)piperidin-4-one (340 mg) as a yellow solid. MS (ESI) m / z = 315.0 (M+H) + Step 2: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)piperidin-4-one The title compound (129 mg) was prepared as a solid in the same manner as in Step 3 of Preparation 17, except that 1-(2-chloro-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)piperidin-4-one (330 mg, 1.048 mmol) prepared in Step 1 was used instead of tert-butyl (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)carbamate. MS (ESI) m / z = 544.0 (M+H) +

[0797] Preparation 29: (1-(2-chloro-5-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol Step 1: tert-Butyl 3-((6-chloro-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate The title compound (550 mg) was prepared as a solid in the same manner as in Preparation 18, except that tert-butyl 3-ethynyl-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate (323 mg, 1.309 mmol) and (1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperidin-4-yl)methanol (400 mg, 1.091 mmol) prepared in Preparation 12 were used instead of 4-ethynyl-1-methylpyrazole and 2-chloro-4-fluoro-5-iodopyridine. MS (ESI) m / z = 486.0 (M+H) + Step 2: (1-(2-chloro-5-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol A 20% TFA solution (5 mL) of tert-butyl 3-((6-chloro-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate (800 mg, 1.646 mmol) prepared in Step 1 in DCM was stirred at room temperature. The reaction mixture was concentrated, and the residue was quenched with saturated NaHCO3 solution, extracted with DCM, dried over MgSO4, and concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-20%) to give (1-(2-chloro-5-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol (480 mg) as an off-white solid. MS (ESI) m / z = 400.2 (M+H) +

[0798] Preparation 30: 4-(4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)benzyl)morpholine The title compound (2.16 g) was prepared as an off-white solid in the same manner as in Preparation 18, except that 4-(4-ethynylbenzyl)morpholine (1.50 g, 7.453 mmol) was used instead of 4-ethynyl-1-methylpyrazole. 1 H-NMR (CDCl3, 400MHz) δ MS (ESI) m / z = 331.1 (M+H) +

[0799] Preparation 31: 1-(4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)benzyl)-4-methylpiperazine The title compound (1.49 g) was prepared as a solid in the same manner as in Preparation 18, except that 1-(4-ethynylbenzyl)-4-methylpiperazine (1.14 g, 5.34 mmol) was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 344.1 (M+H) +

[0800] Preparation 32: 4-(3-(6-chloro-4-fluoropyridin-3-yl)prop-2-yn-1-yl)morpholine The title compound (1169 mg) was prepared as a solid in the same manner as in Preparation 18, except that 4-(2-propyn-1-yl)morpholine (668 mg, 5.341 mmol) was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 255.0 (M+H) +

[0801] Preparation 33: 1-((6-chloro-4-fluoropyridin-3-yl)ethynyl)cyclohexan-1-ol The title compound (505 mg) was prepared as an off-white solid in the same manner as in Preparation 18, except that 1-ethynylcyclohexan-1-ol (300 mg, 2.416 mmol) was used instead of 4-ethynyl-1-methylpyrazole. 1 H-NMR (CDCl3, 400MHz) δ 8.42-8.40 (d, 1H), 7.10-7.08 (d, 1H), 3.24 (s, 1H), 2.01 (s, 1H), 1.74-1.62 (m, 5H), 1.59-1.47 (m, 4H); MS (ESI) m / z = 254.1 (M+H) +

[0802] Preparation 34: 1-((6-chloro-4-fluoropyridin-3-yl)ethynyl)cyclopentan-1-ol The title compound (447 mg) was prepared as an off-white solid in the same manner as in Preparation 18, except that 1-ethynylcyclopentan-1-ol (266 mg, 2.416 mmol) was used instead of 4-ethynyl-1-methylpyrazole.1 H-NMR (CDCl3, 400MHz) δ 8.40-8.37 (d, 1H), 7.07-7.05 (d, 1H), 3.56 (s, 1H), 2.04-1.95 (m, 2H), 1.89-1.88 (d, 2H), 1.86-1.72 (m, 4H); MS (ESI) m / z = 240.1 (M+H) +

[0803] Preparation 35: 2-chloro-4-fluoro-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridine The title compound (296 mg) was prepared as an off-white solid in the same manner as in Preparation 18, except that 4-ethynyltetrahydro-2H-pyran (200 mg, 1.816 mmol) was used instead of 4-ethynyl-1-methylpyrazole. 1 H-NMR (CDCl3, 400MHz) δ 8.42-8.40 (d, 1H), 7.12-7.09 (d, 1H), 3.97-3.93 (m, 2H), 3.60-3.57 (m, 2H), 2.92-2.90 (t, 1H), 1.96-1.90 (m, 2H), 1.82-1.76 (m, 2H); MS (ESI) m / z = 240.1 (M+H) +

[0804] Preparation 36: 2-chloro-4-fluoro-5-((1-methylpyrrolidin-3-yl)ethynyl)pyridine The title compound (131 mg) was prepared as an off-white solid in the same manner as in Preparation 18, except that 3-ethynyl-1-methylpyrrolidine HCl (228 mg, 1.566 mmol) was used instead of 4-ethynyl-1-methylpyrazole. 1H-NMR (CDCl3, 400MHz) δ 8.41-8.38 (q, 1H), 7.10-7.07 (q, 1H), 3.24 (d, 1H), 3.00-2.96 (q, 1H), 2.73-2.68 (q, 1H), 2.60-2.50 (m, 2H), 2.41-2.40 (d, 3H), 2.36-2.29 (q, 1H), 2.04-2.00 (q, 1H); MS (ESI) m / z = 239.1 (M+H) +

[0805] Preparation 37: 4-((5-((6-chloro-4-fluoropyridin-3-yl)ethynyl)thiophen-2-yl)methyl)morpholine The title compound (261 mg) was prepared as an off-white solid in the same manner as in Preparation 18, except that 4-((5-ethynylthiophen-2-yl)methyl)morpholine (300 mg, 1.447 mmol) was used instead of 4-ethynyl-1-methylpyrazole. 1 H-NMR (CDCl3, 400MHz) δ 8.49-8.46 (d, 1H), 7.19-7.18 (d, 1H), 7.14-7.12 (d, 1H), 6.83-6.82 (d, 1H), 3.71-3.70 (d, 4H), 3.69-3.67 (d, 2H), 2.49-2.48 (d, 4H); MS (ESI) m / z = 337.0 (M+H) +

[0806] Preparation 38: 4-((6-((6-chloro-4-fluoropyridin-3-yl)ethynyl)pyridin-3-yl)methyl)morpholine Step 1: 4-((6-ethynylpyridin-3-yl)methyl)morpholine A reaction mixture of 6-ethynylpyridine-3-carbaldehyde (1.0 g, 7.626 mmol) and morpholine (664 mg, 7.626 mmol) in DCE (30 mL) / AcOH (0.1 mL) was stirred at room temperature for 30 min. NaBH(OAc) (2.42 g, 11.439 mmol) was added to the reaction mixture and stirred at room temperature overnight. Saturated NaHCO solution was added to the reaction mixture, which was extracted with DCM, washed with water, dried over MgSO, and concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-80%) to give 4-((6-ethynyl-3-pyridyl)methyl)morpholine (1085 mg) as an off-white solid. 1 H-NMR (CDCl3, 400MHz) δ 8.50 (d, 1H), 7.65-7.63 (q, 1H), 7.43-7.41 (d, 1H), 3.69-3.66 (t, 4H), 3.48 (s, 2H), 2.42-2.40 (t, 4H); MS (ESI) m / z = 203.1 (M+H) + Step 2: 4-((6-((6-chloro-4-fluoropyridin-3-yl)ethynyl)pyridin-3-yl)methyl)morpholine The title compound (466 mg) was prepared as an off-white solid in the same manner as in Preparation 18, except that 4-((6-ethynylpyridin-3-yl)methyl)morpholine (485 mg, 2.398 mmol) prepared in Step 1 was used instead of 4-ethynyl-1-methylpyrazole. 1 H-NMR (CDCl3, 400MHz) δ 8.57 (d, 1H), 7.73-7.70 (q, 1H), 7.67-7.62 (m, 1H), 7.54-7.51 (m, 1H), 7.47-7.44 (q, 1H), 7.17-7.15 (d, 1H), 3.71-3.68 (t, 4H), 3.53 (s, 2H), 2.45-2.43 (t, 4H); MS (ESI) m / z = 332.0 (M+H) +

[0807] Preparation 39: 4-((5-((6-chloro-4-fluoropyridin-3-yl)ethynyl)pyridin-2-yl)methyl)morpholine Step 1: 4-((5-ethynylpyridin-2-yl)methyl)morpholine The title compound (1.22 g) was prepared as an off-white solid in a similar manner to Step 1 of Preparation 38, except that 5-ethynylpicolinaldehyde (1.00 g, 7.626 mmol) was used instead of 6-ethynylpyridine-3-carbaldehyde. 1 H-NMR (CDCl3, 400MHz) δ 8.68-8.67 (d, 1H), 7.76-7.73 (q, 1H), 7.41-7.39 (d, 1H), 3.75-3.73 (t, 4H), 3.66 (s, 2H), 3.20 (s, 1H), 2.52-2.49 (t, 4H); MS (ESI) m / z = 203.1 (M+H) + Step 2: 4-((5-((6-chloro-4-fluoropyridin-3-yl)ethynyl)pyridin-2-yl)methyl)morpholine The title compound (658 mg) was prepared as an off-white solid in the same manner as in Preparation 18, except that 4-((5-ethynylpyridin-2-yl)methyl)morpholine (572 mg, 2.828 mmol) prepared in Step 1 was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 332.0 (M+H) +

[0808] Preparation 40: 4-((4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)thiazol-2-yl)methyl)morpholine Step 1: 4-((4-ethynylthiazol-2-yl)methyl)morpholine The title compound (1.42 g) was prepared as an off-white solid in the same manner as in Step 1 of Preparation 38, except that 4-ethynylthiazole-2-carbaldehyde (1.00 g, 7.291 mmol) was used instead of 6-ethynylpyridine-3-carbaldehyde. 1H-NMR (CDCl3, 400MHz) δ 7.49 (s, 1H), 3.83 (s, 2H), 3.75-3.73 (t, 4H), 3.11 (s, 1H), 2.61-2.59 (t, 4H); MS (ESI) m / z = 209.0 (M+H) + Step 2: 4-((4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)thiazol-2-yl)methyl)morpholine The title compound (491 mg) was prepared as an off-white solid in the same manner as in Preparation 18, except that 4-((4-ethynylthiazol-2-yl)methyl)morpholine (417 mg, 2.002 mmol) prepared in Step 1 was used instead of 4-ethynyl-1-methylpyrazole. 1 H-NMR (CDCl3, 400MHz) δ 8.54-8.52 (d, 1H), 7.59 (s, 1H), 7.14-7.12 (d, 1H), 3.85 (s, 2H), 3.74-3.71 (t, 4H), 2.60-2.58 (t, 4H); MS (ESI) m / z = 338.0 (M+H) +

[0809] Preparation 41: 4-((2-((6-chloro-4-fluoropyridin-3-yl)ethynyl)pyrimidin-5-yl)methyl)morpholine Step 1: 4-((2-ethynylpyrimidin-5-yl)methyl)morpholine The title compound (896 mg) was prepared as an off-white solid in the same manner as in Step 1 of Preparation 38, except that 2-ethynylpyrimidine-5-carbaldehyde (1.00 g, 7.569 mmol) was used instead of 6-ethynylpyridine-3-carbaldehyde. 1 H-NMR (CDCl3, 400MHz) δ 8.69 (s, 1H), 3.78-3.77 (d, 4H), 3.73-3.71 (t, 2H), 3.13 (s, 1H), 2.47-2.45 (t, 4H) Step 2: 4-((2-((6-chloro-4-fluoropyridin-3-yl)ethynyl)pyrimidin-5-yl)methyl)morpholine The title compound (558 mg) was prepared as an off-white solid in the same manner as in Preparation 18, except that 4-((2-ethynylpyrimidin-5-yl)methyl)morpholine (365 mg, 1.752 mmol) prepared in Step 1 was used instead of 4-ethynyl-1-methylpyrazole. 1 H-NMR (CDCl3, 400MHz) δ 8.74-8.73 (d, 2H), 8.65-8.62 (q, 1H), 7.20-7.17 (q, 1H), 3.71-3.70 (d, 4H), 3.54 (s, 2H), 2.46 (s, 4H)

[0810] Preparation 42: 4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)tetrahydro-2H-pyran-4-ol The title compound (687 mg) was prepared as an off-white solid in the same manner as in Preparation 18, except that 4-ethynyltetrahydro-2H-pyran-4-ol (508 mg, 4.029 mmol) was used instead of 4-ethynyl-1-methylpyrazole. 1 H-NMR (CDCl3, 400MHz) δ 8.46-8.44 (d, 1H), 7.15-7.13 (d, 1H), 3.99-3.94 (m, 2H), 3.73-3.67 (m, 2H), 2.09-2.05 (q, 2H), 1.95-1.88 (m, 2H)

[0811] Preparation 43: 2-chloro-4-fluoro-5-((tetrahydrofuran-3-yl)ethynyl)pyridine The title compound (723 mg) was prepared as an off-white solid in the same manner as in Preparation 18, except that 3-ethynyltetrahydrofuran (503 mg, 5.238 mmol) was used instead of 4-ethynyl-1-methylpyrazole. 1 H-NMR (CDCl3, 400MHz) δ 8.37-8.34 (d, 1H), 7.08-7.06 (d, 1H), 4.10-4.03 (m, 1H), 3.96-3.82 (m, 2H), 3.74-3.71 (q, 1H), 3.25-3.18 (m, 1H), 2.32-2.29 (q, 1H), 2.10-2.05 (m, 1H)

[0812] Preparation 44: 5-Bromo-2-chloro-N-isopropylpyridin-4-amine A reaction mixture of 5-bromo-2-chloro-4-iodopyridine (1.00 g, 3.141 mmol), isopropylamine HCl (330 mg, 3.455 mmol), and CsCO (2.05 g, 6.283 mmol) in DMF (5 mL) was stirred at 100 °C for 5 h. The reaction mixture was cooled to room temperature, diluted with DCM, washed with water, dried over MgSO, and concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-50%) to give 5-bromo-2-chloro-N-isopropylpyridin-4-amine (305 mg) as a pale yellow liquid. MS (ESI) m / z = 250.9 (M+H). +

[0813] Preparation 45: (1s,4s)-4-((2-chloro-5-iodopyridin-4-yl)amino)-1-methylcyclohexan-1-ol The title compound (1.33 g) was prepared as a pale yellow liquid in the same manner as in Preparation 2, except that cis-4-amino-1-methylcyclohexanol (1.13 g, 8.74 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 367.0 (M+H) +

[0814] Preparation 46: 2-chloro-4-fluoro-5-(thiophen-3-ylethynyl)pyridine The title compound (715 mg) was prepared as a pale yellow solid in the same manner as in Preparation 18, except that 3-ethynylthiophene (462 mg, 4.273 mmol) was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 237.9 (M+H) +

[0815] Preparation 47: 5-Bromo-2-chloro-4-(1-cyclopropylpyrazol-4-yl)pyridine A reaction mixture of 5-bromo-2-chloro-4-iodo-pyridine (2.00 g, 6.283 mmol), 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (1.76 g, 7.539 mmol), Pd(dppf)Cl (256 mg, 0.314 mmol), and 2M KCO solution (9.42 mL) in 1,4-dioxane (20 mL) was stirred at 90 °C for 3 h. The reaction mixture was cooled, diluted with DCM, washed with water, dried over MgSO, and concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-20%) to give 5-bromo-2-chloro-4-(1-methylpyrazol-4-yl)pyridine (1.30 g) as a white solid. 1 H-NMR (CDCl3, 400MHz) δ 8.52 (s, 1H), 8.10 (s, 1H), 7.90 (s, 1H), 7.38 (s, 1H), 3.69 (s, 1H), 1.21-1.11 (m, 4H); MS (ESI) m / z = 299.0 (M+H) +

[0816] Preparation 48: 5-Bromo-2-chloro-4-(1-methylpyrazol-4-yl)pyridine The title compound (1.3 g) was prepared as an off-white solid in the same manner as in Preparation 47, except that 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.57 g, 7.539 mmol) was used instead of 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1 H-NMR (CDCl3, 400MHz) δ 8.53 (s, 1H), 8.03 (s, 1H), 7.92 (s, 1H), 7.39 (s, 1H), 4.00 (s, 3H); MS (ESI) m / z = 272.9 (M+H) +

[0817] Preparation 49: 4-(4-aminopyrimidin-2-yl)-N,N-dimethyl-1H-pyrazole-1-sulfonamide To a solution of 4-amino-2-chloropyrimidine (250 mg, 1.93 mmol) in 1,4-dioxane (7 mL) was added [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex in dichloromethane (158 mg, 0.1900 mmol), 3M K2CO3 (1.93 mL, 5.79 mmol), and N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-sulfonamide (697 mg, 2.32 mmol). The reaction mixture was stirred at 90 °C for 3 h. The reaction mixture was cooled to room temperature, quenched with water, and extracted with DCM. The organic layer was dried over MgSO4, filtered, and concentrated. The crude residue was purified by silica gel column chromatography (EA / n-Hex = 0-60%) to give 4-(4-aminopyrimidin-2-yl)-N,N-dimethyl-1H-pyrazole-1-sulfonamide (344 mg) as a yellow solid. 1 H-NMR (CDCl3, 400 MHz) δ 8.59 (s, 1H), 8.33 (s, 1H), 8.25 (d, 1H), 6.31 (d, 1H), 4.95 (s, 2H), 2.98 (s, 6H)

[0818] Preparation 50: 4-(4-aminopyrimidin-2-yl)-N,N,3-trimethyl-1H-pyrazole-1-sulfonamide The same procedure as in Preparation 49 was repeated, except that (1-(N,N-dimethylsulfamoyl)-3-methyl-1H-pyrazol-4-yl)boronic acid (647.61 mg, 2.779 mmol) was used instead of N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-sulfonamide, to prepare the title compound (325 mg) as a white solid. MS (ESI) m / z = 283.2 (M+H) +

[0819] Preparation 51: 2-chloro-5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-fluoropyridine The title compound (400 mg) was prepared as a liquid in the same manner as in Preparation 18, except that 1-cyclopropyl-4-ethynyl-1H-pyrazole (257 mg, 1.942 mmol) was used instead of 4-ethynyl-1-methylpyrazole. 1 H-NMR (CDCl3, 400MHz) δ 8.47 (d, 1H), 7.71 (s, 1H), 7.66 (s, 1H), 7.13 (d, 1H), 3.65-3.60 (m, 1H), 1.18-1.04 (m, 4H); MS (ESI) m / z = 272.9 (M+H) +

[0820] Preparation 52: 2-chloro-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-fluoropyridine The title compound (400 mg) was prepared as a liquid in the same manner as in Preparation 18, except that 1-(2,2-difluoroethyl)-4-ethynyl-1H-pyrazole (303 mg, 1.942 mmol) was used instead of 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 285.9 (M+H) +

[0821] Preparation 53: (1-(2-chloro-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol The title compound (154.2 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperidin-4-yl)methanol (150 mg, 0.409 mmol) prepared in Preparation Example 12 and 4-ethynyl-1-(trifluoromethyl)-1H-pyrazole (72.05 mg, 0.45 mmol) were used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine and 4-ethynyl-1-methyl-1H-pyrazole. MS (ESI) m / z = 399.0 (M+H) +

[0822] Preparation 54: 2-chloro-4-fluoro-5-((3-methyloxetan-3-yl)ethynyl)pyridine A mixture of 2-chloro-4-fluoro-5-iodopyridine (1.41 g, 5.461 mmol), 3-ethynyl-3-methyloxetane (0.50 g, 5.201 mmol), PdCl(PPh) (182 mg, 0.260 mmol), and CuI (198 mg, 1.040 mmol) was purged with nitrogen gas for 10 min. DMF (30 mL) and TEA (1.45 mL, 10.403 mmol) were added, and the reaction mixture was stirred at 50 °C overnight. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO, and concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-40%) to give 2-chloro-4-fluoro-5-((3-methyloxetan-3-yl)ethynyl)pyridine (0.52 g) as an off-white solid. 1 H-NMR (CDCl3, 400 MHz) δ 8.43-8.41 (d, 1H), 7.13-7.11 (d, 1H), 4.93-4.92 (d, 2H), 4.50-4.49 (d, 2H), 1.73 (s, 3H)

[0823] Preparation 55: 1-((6-chloro-4-fluoropyridin-3-yl)ethynyl)cyclobutan-1-ol The title compound (476 mg) was prepared as a solid in the same manner as in Preparation 54, except that 1-ethynylcyclobutan-1-ol (500 mg, 5.201 mmol) was used instead of 3-ethynyl-3-methyloxetane. 1 H-NMR (CDCl3, 400 MHz) δ 8.43-8.41 (d, 1H), 7.11-7.09 (d, 1H), 2.55-2.52 (m, 2H), 2.39-2.31 (m, 2H), 1.90-1.82 (m, 2H)

[0824] Preparation 56: 2-chloro-4-fluoro-5-(oxetan-3-ylethynyl)pyridine The title compound (712 mg) was prepared as a solid in the same manner as in Preparation 54, except that 3-ethynyloxetane (555 mg, 6.762 mmol) was used instead of 3-ethynyl-3-methyloxetane. 1 H-NMR (CDCl3, 400 MHz) δ 8.40-8.37 (d, 1H), 7.10-7.07 (d, 1H), 4.87-4.84 (q, 2H), 4.79-4.76 (q, 2H), 4.12-4.04 (m, 1H)

[0825] Preparation 57: 3-((6-chloro-4-fluoropyridin-3-yl)ethynyl)oxetan-3-ol The title compound (674 mg) was prepared as a solid in the same manner as in Preparation 54, except that 3-ethynyl-3-oxetanol (490 mg, 4.996 mmol) was used instead of 3-ethynyl-3-methyloxetane. 1 H-NMR (CDCl3, 400 MHz) δ 8.49-8.47 (d, 1H), 7.17-7.15 (d, 1H), 4.95-4.94 (d, 2H), 4.82-4.81 (d, 2H), 3.48 (s, 1H)

[0826] Preparation 58: 3-((6-chloro-4-fluoropyridin-3-yl)ethynyl)tetrahydrofuran-3-ol The title compound (712 mg) was prepared as a solid in the same manner as in Preparation 54, except that 3-ethynyltetrahydrofuran-3-ol (560 mg, 4.996 mmol) was used instead of 3-ethynyl-3-methyloxetane. 1 H-NMR (CDCl3, 400 MHz) δ 8.47-8.44 (d, 1H), 7.15-7.13 (d, 1H), 4.15-4.07 (m, 2H), 4.05-3.96 (m, 2H), 2.80-2.72 (t, 1H), 2.47-2.32 (m, 2H)

[0827] Preparation 59: 3-((6-chloro-4-fluoropyridin-3-yl)ethynyl)tetrahydro-2H-pyran-3-ol The title compound (310 mg) was prepared as a solid in the same manner as in Preparation 54, except that 3-ethynyltetrahydro-2H-pyran-3-ol (500 mg, 3.964 mmol) was used instead of 3-ethynyl-3-methyloxetane. 1 H-NMR (CDCl3, 400 MHz) δ 8.46-8.43 (d, 1H), 7.13-7.11 (d, 1H), 3.79-3.63 (m, 4H), 3.01 (s, 1H), 2.08-2.00 (m, 2H), 1.93-1.86 (m, 1H), 1.78-1.72 (q, 1H)

[0828] Preparation 60: 2-chloro-4-fluoro-5-((1-methylcyclopropyl)ethynyl)pyridine The title compound (1105 mg) was prepared as a solid in the same manner as in Preparation 54, except that 1-ethynyl-1-methylcyclopropane (500 mg, 6.240 mmol) was used instead of 3-ethynyl-3-methyloxetane. 1 H-NMR (CDCl3, 400 MHz) δ 8.38-8.35 (d, 1H), 7.08-7.06 (d, 1H), 1.37 (s, 3H), 1.07-1.04 (q, 2H), 0.94-0.91 (q, 2H)

[0829] Preparation 61: 2-chloro-4-fluoro-5-((tetrahydrofuran-2-yl)ethynyl)pyridine The title compound (789 mg) was prepared as a solid in the same manner as in Preparation 54, except that 2-ethynyloxolane (500 mg, 5.202 mmol) was used instead of 3-ethynyl-3-methyloxetane. 1 H-NMR (CDCl3, 400 MHz) δ 8.44-8.42 (d, 1H), 7.12-7.10 (d, 1H), 4.86-4.83 (m, 1H), 4.01-3.98 (t, 1H), 3.92-3.82 (m, 1H), 2.28-2.23 (m, 1H), 2.14-2.07 (m, 2H), 2.02-1.95 (m, 1H)

[0830] Preparation 62: 2-chloro-4-fluoro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridine The title compound (437 mg) was prepared as a solid in the same manner as in Preparation 54, except that 4-ethynyl-1-(2-fluoroethyl)pyrazole (282 mg, 2.039 mmol) was used instead of 3-ethynyl-3-methyloxetane. MS (ESI) m / z = 268.1 (M+H) +

[0831] Preparation 63: (S)-1-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)-N,N-dimethylmethanamine The title compound (1059 mg) was prepared as a solid in the same manner as in Preparation 2, except that (R)-N,N-dimethyl-1-(piperidin-3-yl)methanamine dihydrochloride (580 mg, 4.079 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 380.0 (M+H) +

[0832] Preparation 64: 2-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)-N,N-dimethylethan-1-amine The title compound (1318 mg) was prepared as a solid in the same manner as in Preparation 2, except that N,N-dimethyl-2-(piperidin-3-yl)ethan-1-amine dihydrochloride (934 mg, 4.079 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 394.0 (M+H) +

[0833] Preparation 65: 2-chloro-4-fluoro-5-((1-(methylsulfonyl)piperidin-4-yl)ethynyl)pyridine Step 1: tert-Butyl 4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)piperidine-1-carboxylate The title compound (9500 mg) was prepared as a solid in the same manner as in Preparation 54, except that 1-boc-4-ethynylpiperidine (6429 mg, 30.720 mmol) was used instead of 3-ethynyl-3-methyloxetane. 1 H-NMR (CDCl3, 400 MHz) δ 8.28-8.25 (d, 1H), 7.00-6.98 (d, 1H), 3.63-3.59 (m, 2H), 3.18-3.12 (m, 2H), 2.76-2.74 (t, 1H), 1.78-1.73 (m, 2H), 1.59-1.55 (m, 2H), 1.34 (s, 9H) Step 2: 2-Chloro-4-fluoro-5-(piperidin-4-ylethynyl)pyridine hydrochloride tert-Butyl 4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)piperidine-1-carboxylate (9.50 g, 28.04 mmol) prepared in Step 1 was dissolved in 4.0 M HCl in 1,4-dioxane (26.8 mL) and stirred at room temperature for 2 hours. After the reaction mixture was concentrated, the residue was dissolved in EtOAc (20 mL). The reaction mixture was concentrated. The crude product was triturated with diethyl ether to give 2-chloro-4-fluoro-5-(piperidin-4-ylethynyl)pyridine hydrochloride (6160 mg) as a white solid. 1 H-NMR (CDCl3, 400 MHz) δ 10.10-9.99 (d, 2H), 8.48-8.45 (d, 1H), 7.12-7.10 (d, 1H), 3.70 (s, 1H), 3.56 (s, 1H), 3.49-3.46 (t, 3H), 3.37 (s, 1H), 2.45-2.42 (t, 2H), 2.24-2.20 (q, 2H) Step 3: 2-chloro-4-fluoro-5-((1-(methylsulfonyl)piperidin-4-yl)ethynyl)pyridine To a solution of 2-chloro-4-fluoro-5-(piperidin-4-ylethynyl)pyridine hydrochloride (750 mg, 3.140 mmol) prepared in Step 2 in DCM (10 mL) was added methanesulfonyl chloride (0.27 mL, 3.46 mmol) and TEA (1.31 mL, 9.43 mmol). The reaction mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with DCM. The combined organic layers were washed with brine, dried over MgSO4, and concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-100%) to give 2-chloro-4-fluoro-5-((1-(methylsulfonyl)piperidin-4-yl)ethynyl)pyridine (606 mg) as a yellow solid. MS (ESI) m / z = 317.0 (M+H) +

[0834] Preparation 66: 2-chloro-5-((1-(cyclopropylsulfonyl)piperidin-4-yl)ethynyl)-4-fluoropyridine The title compound (853 mg) was prepared as a solid in a manner similar to Step 3 of Preparation 65, except that cyclopropanesulfonyl chloride (0.35 mL, 3.46 mmol) was used instead of methanesulfonyl chloride. MS (ESI) m / z = 343.0 (M+H) +

[0835] Preparation 67: 2-chloro-5-((1-(cyclopropylsulfonyl)pyrrolidin-3-yl)ethynyl)-4-fluoropyridine Step 1: tert-Butyl 3-((6-chloro-4-fluoropyridin-3-yl)ethynyl)pyrrolidine-1-carboxylate The title compound (8730 mg) was prepared as a solid in the same manner as in Preparation 54, except that tert-butyl-3-ethynylpyrrolidine-1-carboxylate (6000 mg, 30.72 mmol) was used instead of 3-ethynyl-3-methyloxetane. 1H-NMR (CDCl3, 400 MHz) δ 8.38-8.35 (d, 1H), 7.09-7.07 (d, 1H), 3.70-3.65 (t, 1H), 3.56 (s, 1H), 3.40-3.36 (d, 2H), 3.23-3.20 (d, 1H), 2.24-2.18 (q, 1H), 2.04-1.95 (t, 1H), 1.44 (s, 9H) Step 2: 2-Chloro-4-fluoro-5-(pyrrolidin-3-ylethynyl)pyridine hydrochloride The title compound (6450 mg) was prepared as a white solid in the same manner as in Step 2 of Preparation 65, except that tert-butyl 3-((6-chloro-4-fluoropyridin-3-yl)ethynyl)pyrrolidine-1-carboxylate (8.73 g, 26.88 mmol) prepared in Step 1 was used instead of tert-butyl 4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)piperidine-1-carboxylate. 1 H-NMR (CDCl3, 400 MHz) δ 9.66 (s, 2H), 8.42-8.39 (q, 1H), 7.14-7.11 (q, 1H), 3.39 (s, 2H), 3.27 (s, 2H), 3.11 (s, 1H), 2.34-2.29 (m, 2H), 2.11-2.07 (q, 2H) Step 3: 2-chloro-5-((1-(cyclopropylsulfonyl)pyrrolidin-3-yl)ethynyl)-4-fluoropyridine The title compound (826 mg) was prepared as a yellow solid in the same manner as in Step 3 of Preparation 65, except that 2-chloro-4-fluoro-5-(pyrrolidin-3-ylethynyl)pyridine hydrochloride (760 mg, 3.38 mmol) prepared in Step 2 and cyclopropanesulfonyl chloride (0.38 mL, 3.72 mmol) were used instead of 2-chloro-4-fluoro-5-(piperidin-4-ylethynyl)pyridine hydrochloride and methanesulfonyl chloride. MS (ESI) m / z = 329.0 (M+H) +

[0836] Preparation 68: 2-chloro-4-fluoro-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridine The title compound (1920 mg) was prepared as a solid in a similar manner to Step 3 of Preparation 67, except using methanesulfonyl chloride (0.65 mL, 8.31 mmol) instead of cyclopropanesulfonyl chloride. 1 H-NMR (CDCl3, 400 MHz) δ 8.39-8.37 (d, 1H), 7.11-7.09 (d, 1H), 3.72-3.68 (q, 1H), 3.52-3.41 (m, 4H), 3.34-3.31 (t, 1H), 3.09-3.08 (d, 1H), 2.87 (d, 3H), 2.33-2.30 (t, 1H), 2.19-2.15 (t, 1H), 1.47-1.37 (q, 2H)

[0837] Preparation 69: 1-(3-((6-chloro-4-fluoropyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one The title compound (1248 mg) was prepared as a solid in the same manner as in Preparation 54, except that 1-(3-ethynylpyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one (1000 mg, 5.23 mmol) was used instead of 3-ethynyl-3-methyloxetane. MS (ESI) m / z = 321.0 (M+H) +

[0838] Preparation 70: 2-chloro-4-fluoro-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine The title compound (1540 mg) was prepared as a solid in the same manner as in Preparation 54, except that (2R)-3-ethynyl-2-(trifluoromethyl)tetrahydrofuran (1000 mg, 6.09 mmol) was used instead of 3-ethynyl-3-methyloxetane. MS (ESI) m / z = 293.0 (M+H) +

[0839] Preparation 71: 5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-chloro-4-fluoropyridine The title compound (1490 mg) was prepared as a solid in the same manner as in Preparation 54, except that 2-ethynyl-7-oxabicyclo[2.2.1]heptane (744 mg, 6.09 mmol) was used instead of 3-ethynyl-3-methyloxetane. MS (ESI) m / z = 252.0 (M+H) +

[0840] Preparation 72: 3-((6-chloro-4-fluoropyridin-3-yl)ethynyl)tetrahydrothiophene 1,1-dioxide The title compound (1107 mg) was prepared as a solid in the same manner as in Preparation 54, except that 3-ethynyl-1-lambda-6-thiolane-1,1-dione (1000 mg, 6.94 mmol) was used instead of 3-ethynyl-3-methyloxetane. MS (ESI) m / z = 274.0 (M+H) +

[0841] Preparation 73: 2-chloro-4-fluoro-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine The title compound (983 mg) was prepared as a solid in the same manner as in Preparation 54, except that 3-ethynyl-2-methyloxolane (763 mg, 6.94 mmol) was used instead of 3-ethynyl-3-methyloxetane. MS (ESI) m / z = 240.0 (M+H) +

[0842] Preparation 74: 2-chloro-4-fluoro-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridine The title compound (1359 mg) was prepared as a solid in the same manner as in Preparation 54, except that 3-ethynyl-3-fluorooxolane (792 mg, 6.94 mmol) was used instead of 3-ethynyl-3-methyloxetane. MS (ESI) m / z = 244.0 (M+H) +

[0843] Preparation 75: (4-((6-chloro-4-fluoropyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone The title compound (1121 mg) was prepared as a solid in the same manner as in Preparation 54, except that (4-ethynylphenyl)-(4-hydroxy-1-piperidinyl)methanone (1000 mg, 4.36 mmol) was used instead of 3-ethynyl-3-methyloxetane. MS (ESI) m / z = 359.1 (M+H) +

[0844] Example 1: 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-methylpiperazin-1-yl)pyridin-2-yl)pyrimidin-4-amine Step 1: 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine A suspension of 2,4-dichloro-5-iodopyridine (400 mg, 1.460 mmol), 1-methylpiperazine (0.24 mL, 2.191 mmol), and DIPEA (0.51 mL, 2.921 mmol) in DMA (7 mL) was stirred at 100 °C overnight. After cooling, the reaction mixture was diluted with EA, washed with water, dried over MgSO4, and concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-15%) to give 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine (364 mg) as a yellow solid. MS (ESI) m / z = 338.0 (M+H). + Step 2: 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine A mixture of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine (290 mg, 0.859 mmol), 4-ethynyl-1-methylpyrazole (109.4 mg, 1.031 mmol), PdCl(PPh) (30.15 mg, 0.043 mmol), and CuI (32 mg, 0.172 mmol) was purged with nitrogen for 10 min. DMF (6 mL) and TEA (0.24 mL, 1.718 mmol) were added, and the reaction mixture was stirred at 50 °C for 1 h. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO, and concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-10%) to give 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine (114 mg) as a yellow solid. MS (ESI) m / z = 316.1 (M+H) + Step 3: 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-methylpiperazin-1-yl)pyridin-2-yl)pyrimidin-4-amine A suspension of 2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-amine (111 mg, 0.418 mmol), 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine (110 mg, 0.348 mmol) prepared in Step 2, CsCO (227 mg, 0.697 mmol), XPhos (33 mg, 0.070 mmol), and Pd(dba) (32 mg, 0.035 mmol) in 1,4-dioxane (4 mL) was stirred overnight at 80 °C. The reaction mixture was cooled, filtered through Celite, and concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-20%) to give 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-methylpiperazin-1-yl)pyridin-2-yl)pyrimidin-4-amine (28.5 mg) as a yellow solid. 1 H-NMR (CDCl3, 600 MHz) δ 8.65 (s, 1H), 8.44 (s, 1H), 8.41 (d, 1H), 8.26 (s, 1H), 7.63 (s, 1H), 7.62 (s, 1H), 7.56 (s, 1H), 7.49 (s, 1H), 7.08 MS (ESI) m / z = 545.2 (M+H) +

[0845] Example 2: N 4 -Cyclohexyl-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine Step 1: 2-Chloro-N-cyclohexyl-5-iodopyridin-4-amine The title compound (176 mg) was prepared as a solid in a manner similar to Step 1 of Example 1, except that cyclohexylamine (217 mg, 2.191 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 337.0 (M+H) + Step 2: 2-chloro-N-cyclohexyl-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine The title compound (88.7 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 2-chloro-N-cyclohexyl-5-iodopyridin-4-amine (176 mg, 0.523 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 315.0 (M+H) + Step 3:N 4 -Cyclohexyl-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine The title compound (17.5 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-chloro-N-cyclohexyl-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine (88 mg, 0.280 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (CDCl3, 600 MHz) δ 8.65 (s, 1H), 8.44 (s, 1H), 8.41 (d, 1H), 8.26 (s, 1H), 7.63 (s, 1H), 7.62 (s, 1H), 7.56 (s, 1H), 7.49 (s, 1H), 7.08 MS (ESI) m / z = 544.2 (M+H) +

[0846] Example 3: 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(ethylsulfonyl)piperazin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine Step 1: 1-(2-chloro-5-iodopyridin-4-yl)-4-(ethylsulfonyl)piperazine The title compound (115 mg) was prepared as a solid in a manner similar to Step 1 of Example 1, except that 1-ethanesulfonyl piperazine (390 mg, 2.191 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 416.1 (M+H) + Step 2: 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-(ethylsulfonyl)piperazine The title compound (100 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 1-(2-chloro-5-iodopyridin-4-yl)-4-(ethylsulfonyl)piperazine (115 mg, 0.277 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 394.0 (M+H) + Step 3: 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(ethylsulfonyl)piperazin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine The title compound (10.4 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-(ethylsulfonyl)piperazine (100 mg, 0.254 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.64 (s, 1H), 8.43 (s, 1H), 8.42 (s, 1H), 8.28 (s, 1H), 8.03 (s, 1H), 7.62 (s, 1H), 7.60 (s, 1H), 7.56 (s, 1H), 7.04 MS (ESI) m / z = 623.2 (M+H) +

[0847] Example 4: (R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)butan-1-ol Step 1: (R)-3-((2-chloro-5-iodopyridin-4-yl)amino)butan-1-ol The title compound (451 mg) was prepared as a solid in the same manner as in Step 1 of Example 1, except that (3R)-3-aminobutan-1-ol (866 mg, 9.711 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 327.0 (M+H)+ Step 2: (R)-3-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)butan-1-ol The title compound (86.52 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (R)-3-((2-chloro-5-iodopyridin-4-yl)amino)butan-1-ol (228 mg, 0.698 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 305.1 (M+H) + Step 3: (R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)butan-1-ol The title compound (81 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (R)-3-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)butan-1-ol (184 mg, 0.604 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.69 (s, 1H), 8.47 (s, 1H), 8.39 (d, 1H), 8.09 (d, 1H), 7.58 (s, 1H), 7.54 (s, 1H), 7.44 (s, 1H), 7.35 (s, 1H), 7.01 (s, 1H), 5.40 (d, 1H), 4.02-4.00 (m, 1H), 3.93 (s, 3H), 3.90-3.83 (m, 2H), 2.96-2.82 (m, 1H), 2.05-1.99 (m, 1H), 1.98-1.84 (m, 1H), 1.55 (s, 3H), 1.38 (d, 4H), 1.27-1.20 (m, 2H); MS (ESI) m / z = 534.2 (M+H) +

[0848] Example 5: (S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-2-methylbutan-2-ol Step 1: (S)-3-((2-chloro-5-iodopyridin-4-yl)amino)-2-methylbutan-2-ol The title compound (429 mg) was prepared as a solid in a similar manner to Step 1 of Example 1, except that (S)-3-amino-2-methylbutan-2-ol HCl (1.36 g, 9.711 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 341.0 (M+H) + Step 2: (S)-3-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-2-methylbutan-2-ol The title compound (291 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (S)-3-((2-chloro-5-iodopyridin-4-yl)amino)-2-methylbutan-2-ol (350 mg, 1.028 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 319.0 (M+H) + Step 3: (S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-2-methylbutan-2-ol The title compound (75 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (S)-3-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-2-methylbutan-2-ol (290 mg, 0.910 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.63 (s, 1H), 8.46 (s, 1H), 8.37 (s, 1H), 8.10 (s, 1H), 7.64 (s, 1H), 7.57 (s, 1H), 7.21 (s, 1H), 7.06 (s, 1H), 5.47 MS (ESI) m / z = 534.2 (M+H) +

[0849] Example 6: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol Step 1: 1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-ol The title compound (320 mg) was prepared as a solid in a manner similar to Step 1 of Example 1, except that 3-hydroxypiperidine (255 mg, 2.525 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 339.0 (M+H) + Step 2: 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol The title compound (170 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-ol (208 mg, 0.614 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 317.1 (M+H) + Step 3: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol The title compound (77 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol (170 mg, 0.537 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (DMSO-d6, 600 MHz) δ 10.23 (s, 1H), 8.67 (s, 1H), 8.45 (s, 1H), 8.44 (d, 1H), 8.15 (s, 1H), 8.00 (s, 1H), 7.66 (s, 1H), 7.54 (s, 1H), 7.41 (s, 1H), 4.97 (d, 1H), 4.00 (d, 1H), 3.85 (s, 3H), 3.67 (d, 2H), 3.27-3.24 (m, 1H), 2.96 (t, 1H), 2.69 (t, 1H), 1.97-1.95 (m, 1H), 1.86-1.84 (m, 1H), 1.60-1.58 (m, 1H), 1.37-1.33 (m, 2H), 1.26-1.24 (m, 2H); MS (ESI) m / z = 546.2 (M+H) +

[0850] Example 7: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-one Step 1: 1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-one The title compound (1.54 g) was prepared as a solid in a manner similar to Step 1 of Example 1, except that piperidin-4-one HCl hydrate (1.43 g, 9.323 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 337.0 (M+H) + Step 2: 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-one The title compound (720 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-one (1.00 g, 2.971 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 315.0 (M+H) + Step 3: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-one The title compound (230 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-one (700 mg, 2.224 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (DMSO-d6, 600 MHz) δ 10.30 (s,1H), 8.67 (s, 1H), 8.45 (s, 1H), 8.44 (s, 1H), 8.22 (s, 1H), 8.05 (s, 1H), 7.77 (s,1H), 7.67 (s, 1H), 7.35 (s, 1H), 3.87 (s, 3H), 3.80 (t, 4H), 3.27-3.23 (m, 1H), 2.59 (t, 4H), 1.34-1.30 (m, 2H), 1.26-1.21 (m, 2H); MS (ESI) m / z = 544.1 (M+H) +

[0851] Example 8: 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoropiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine Step 1: 2-chloro-4-(4-fluoropiperidin-1-yl)-5-iodopyridine The title compound (686 mg) was prepared as a solid in a manner similar to Step 1 of Example 1, except that 4-fluoropiperidine HCl (423 mg, 3.030 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 322.3 (M+H). + Step 2: 2-chloro-4-(4-fluoropiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine The title compound (163 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 2-chloro-4-(4-fluoropiperidin-1-yl)-5-iodopyridine (220 mg, 0.646 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 319.0 (M+H) + Step 3: 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoropiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine The title compound (84.9 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-chloro-4-(4-fluoropiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine (163 mg, 0.511 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.65 (s, 1H), 8.44 (s, 1H), 8.42 (d, 1H), 8.26 (s, 1H), 8.24 (s, 1H), 7.63 (s, 1H), 7.56 (s, 2H), 7.05 (s, 1H), 4.92 MS (ESI) m / z = 548.2 (M+H) +

[0852] Example 9: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol Step 1: (1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)methanol The title compound (732 mg) was prepared as a solid in the same manner as in Step 1 of Example 1, except that 3-piperidinemethanol (349 mg, 3.030 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 353.0 (M+H) + Step 2: (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol The title compound (153 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)methanol (240 mg, 0.681 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 3: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol The title compound (34.4 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol (153 mg, 0.463 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.66 (s, 1H), 8.49 (s, 1H), 8.40 (d, 1H), 8.22 (s, 1H), 8.03 (s, 1H), 7.65 (s, 1H), 7.60 (s, 2H), 6.98 (s, 1H), 4.13 (d, 1H), 3.97 (d, 1H), 3.92 (s, 3H), 3.76-3.67 (m, 1H), 3.62-3.58 (m, 1H), 2.97-2.93 (m, 1H), 2.85-2.82 (m, 1H), 2.81-2.77 (m, 1H), 2.04 (s, 1H), 1.93-1.77 (m, 4H), 1.54 (s, 2H), 1.32-1.21 (m, 2H), 1.20 (s, 2H); MS (ESI) m / z = 560.2 (M+H)+

[0853] Example 10: 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol Step 1: 1-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)ethan-1-ol The title compound (521 mg) was prepared as a solid in the same manner as in Step 1 of Example 1, except that 1-(4-piperidyl)ethanol (391 mg, 3.03 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 367.0 (M+H) + Step 2: 1-(1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol The title compound (224 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 1-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)ethan-1-ol (300 mg, 0.818 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 345.1 (M+H) + Step 3: 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol The title compound (57.6 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 1-(1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol (220 mg, 0.638 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.67 (s, 1H), 8.45 (s 1H), 8.41 (d, 1H), 8.23 ​​(d, 1H), 7.99 (s, 1H), 7.63 (s, 1H), 7.55 (s, 2H), 7.03 (s, 1H), 4.22-4.16 (m, 2H), 3.93 (s, 3H), 3.68 (t, 1H), 2.91-2.82 (m, 3H), 2.07 (d, 1H), 1.85 (d, 1H), 1.73 (s, 3H), 1.55-1.51 (m, 5H), 1.26-1.25 (m, 3H), 1.23-1.21 (m, 2H); MS (ESI) m / z = 574.2 (M+H) +

[0854] Example 11: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)propan-2-ol Step 1: 2-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)propan-2-ol The title compound (748 mg) was prepared as a solid in a manner similar to Step 1 of Example 1, except that 2-(piperidin-4-yl)propan-2-ol (434 mg, 3.030 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 381.0 (M+H) + Step 2: 2-(1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)propan-2-ol The title compound (236 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 2-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)propan-2-ol (300 mg, 0.788 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 359.1 (M+H) + Step 3: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)propan-2-ol The title compound (94.4 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-(1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)propan-2-ol (236 mg, 0.657 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.67 (s, 1H), 8.45 (s, 1H), 8.40 (d, 1H), 8.24 (s, 1H), 8.17 (s, 1H), 7.63 (s, 1H), 7.58 (s, 1H), 7.55 (s, 1H), 7.01 (s, 1H), 4.23 (d, 2H), 3.94 (s, 3H), 2.87-2.83 (m, 3H), 1.98 (d, 2H), 1.81 (s, 2H), 1.59-1.53 ​​(m, 3H), 1.52-1.51 (m, 2H), 1.25 (s, 6H), 1.23-1.20 (m, 2H); MS (ESI) m / z = 588.3 (M+H) +

[0855] Example 12: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol Step 1: (1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperidin-4-yl)methanol The title compound (667 mg) was prepared as a solid in the same manner as in Step 1 of Example 1, except that (4-methylpiperidin-4-yl)methanol (391 mg, 3.03 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 367.0 (M+H) + Step 2: (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol The title compound (221 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperidin-4-yl)methanol (300 mg, 0.818 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 345.1 (M+H) + Step 3: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol The title compound (46.7 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol (220 mg, 0.638 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.66 (s, 1H), 8.45 (s, 1H), 8.41 (d, 1H), 8.23 ​​(s, 1H), 7.92 (s, 1H), 7.63 (s, 2H), 7.55 (s, 1H), 6.97 (s, 1H), 3.93 (s, 3H), 3.70-3.67 (m, 2H), 3.51 (s, 2H), 3.40 (t, 2H), 2.85-2.82 (m, 1H), 1.80-1.76 (m, 2H), 1.59-1.57 (m, 2H), 1.54-1.52 (m, 2H), 1.27-1.22 (m, 2H), 1.09 (s, 3H); MS (ESI) m / z = 574.2 (M+H) +

[0856] Example 13: 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol Step 1: 7-(2-chloro-5-iodopyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol The title compound (581 mg) was prepared as a solid in the same manner as in Step 1 of Example 1, except that 2-methyl-7-azaspiro[3.5]nonan-2-ol (470 mg, 3.030 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 393.0 (M+H) + Step 2: 7-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol The title compound (184 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 7-(2-chloro-5-iodopyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol (300 mg, 0.764 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 371.2 (M+H) + Step 3: 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol The title compound (82.6 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 7-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol (183 mg, 0.493 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (CDCl3, 600 MHz) δ 8.65 (s, 1H), 8.45 (s, 1H), 8.40 (d, 1H), 8.23 ​​(s, 1H), 8.18 (s, 1H), 7.63 (s, 1H), 7.59 (s, 1H), 7.55 (s, 1H), 6.98 (s, 1H), 3.94 (s, 3H), 3.46-3.41 (m, 4H), 2.86-2.83 (m, 1H), 2.07 (d, 2H), 2.03 (d, 2H), 1.91 (t, 2H), 1.81 (s, 1H), 1.80 (t, 3H), 1.54-1.51 (m, 2H), 1.44 (s, 3H), 1.27-1.21 (m, 2H); MS (ESI) m / z = 600.3 (M+H) +

[0857] Example 14: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol Step 1: 2-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol The title compound (775 mg) was prepared as a solid in the same manner as in Step 1 of Example 1, except that 2-methyl-2-(4-piperidyl)propan-1-ol (476 mg, 3.030 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 395.0 (M+H) + Step 2: 2-(1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol The title compound (204 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 2-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol (300 mg, 0.760 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 373.1 (M+H) + Step 3: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol The title compound (45 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-(1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol (203 mg, 0.544 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.68 (s, 1H), 8.46 (s, 1H), 8.41 (d, 1H), 8.23 ​​(s, 1H), 8.02 (s, 1H), 7.64 (s, 2H), 7.55 (s, 1H), 6.98 (s, 1H), 4.21 MS (ESI) m / z = 602.2 (M+H) +

[0858] Example 15: 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-methoxypiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine Step 1: 2-chloro-5-iodo-4-(4-methoxypiperidin-1-yl)pyridine The title compound (763 mg) was prepared as a solid in a manner similar to Step 1 of Example 1, except that 4-methoxypiperidine (349 mg, 3.030 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 353.0 (M+H) + Step 2: 2-chloro-4-(4-methoxypiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine The title compound (331 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 2-chloro-5-iodo-4-(4-methoxypiperidin-1-yl)pyridine (500 mg, 1.418 mmol) was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H). + Step 3: 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-methoxypiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine The title compound (230 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-chloro-4-(4-methoxypiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine (330 mg, 0.998 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (CDCl3, 600 MHz) δ 8.66 (s, 1H), 8.45 (s, 1H), 8.41 (d, 1H), 8.24 (s, 1H), 8.16 (s, 1H), 7.65 (s, 1H), 7.57 (s, 2H), 7.03 (s, 1H), 3.93 (s, 3H), 3.89-3.84 (m, 2H), 3.48-3.47 (m, 1H), 3.46-3.45 (m, 3H), 3.23-3.20 (m, 2H), 2.85-2.82 (m, 2H), 2.13-2.07 (m, 2H), 1.84-1.77 (m, 4H), 1.55-1.52 (m, 2H), 1.26-1.21 (m, 2H); MS (ESI) m / z = 560.2 (M+H) +

[0859] Example 16: 2-(4-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperazin-1-yl)ethan-1-ol Step 1: 2-(4-(2-chloro-5-iodopyridin-4-yl)piperazin-1-yl)ethan-1-ol The title compound (443 mg) was prepared as a solid in a similar manner to Step 1 of Example 1, except that 2-(piperazin-1-yl)ethan-1-ol (285 mg, 2.191 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 368.1 (M+H) + Step 2: 2-(4-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperazin-1-yl)ethan-1-ol The title compound (201 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 2-(4-(2-chloro-5-iodopyridin-4-yl)piperazin-1-yl)ethan-1-ol (430 mg, 1.170 mmol) and 4-ethynyl-1-(2-fluoroethyl)pyrazole (178 mg, 1.287 mmol) prepared in Step 1 were used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine and 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 378.2 (M+H) + Step 3: 2-(4-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperazin-1-yl)ethan-1-ol The title compound (4.4 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-(4-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperazin-1-yl)ethan-1-ol (200 mg, 0.529 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.67 (s, 1H), 8.45 (s, 1H), 8.43 (d, 1H), 8.25 (s, 1H), 7.77 (s, 1H), 7.67 (s, 2H), 7.55 (s, 1H), 7.05 (d, 1H), 4.83 (t, 1H), 4.75 (t, 1H), 4.46 (t, 1H), 4.42 (t, 1H), 3.69 (t, 2H), 3.61 (s, 4H), 2.87-2.82 (m, 1H), 2.77 (t, 4H), 2.66-2.18 (m, 2H), 1.56-1.53 (m, 2H), 1.31-1.22 (m, 2H); MS (ESI) m / z = 607.3 (M+H) +

[0860] Example 17: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol Step 1: 2-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)ethan-1-ol The title compound (325 mg) was prepared as a solid in the same manner as in Step 1 of Example 1, except that 4-piperidineethanol (283 mg, 2.191 mmol) was used instead of 1-methylpiperazine. MS (ESI) m / z = 367.0 (M+H) + Step 2: 2-(1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol The title compound (86 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 2-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)ethan-1-ol (140 mg, 0.382 mmol) and 4-ethynyl-1-(2-fluoroethyl)pyrazole (53 mg, 0.382 mmol) prepared in Step 1 were used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine and 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 345.2 (M+H) + Step 3: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol The title compound (4.5 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-(1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol (86 mg, 0.227 mmol) prepared in Step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.67 (s, 1H), 8.45 (s, 1H), 8.41 (s, 1H), 8.21 (s, 1H), 7.90 (s, 1H), 7.68 (d, 2H), 7.58 (s, 1H), 7.07 (d, 1H), 4.83 (t, 1H), 4.75 (t, 1H), 4.46 (t, 1H), 4.42 (t, 1H), 4.12 (d, 2H), 3.78-3.76 (m, 2H), 2.96-2.91 (m, 2H), 2.89-2.84 (m, 1H), 1.93-1.87 (m, 2H), 1.76-1.73 (m, 2H), 1.63-1.57 (m, 2H), 1.56-1.53 ​​(m, 2H), 1.36-1.34 (m, 2H), 1.28-1.21 (m, 2H); MS (ESI) m / z = 606.2 (M+H) +

[0861] Example 18: N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -Isopropyl-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine Step 1: 2-chloro-N-isopropyl-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine The title compound (237 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 2-chloro-5-iodo-N-isopropylpyridin-4-amine (285 mg, 0.961 mmol) was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 275.1 (M+H). + Step 2:N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -Isopropyl-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine The title compound (89 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-chloro-N-isopropyl-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine (107 mg, 0.39 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.64 (s, 1H), 8.45 (s, 1H), 8.39 (d, 1H), 8.34 (s, 1H), 8.13 (s, 1H), 7.66 (s, 1H), 7.60 (s, 1H), 7.32 (s, 1H) 7.01 MS (ESI) m / z = 504.0 (M+H) +

[0862] Example 19: N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -Isopropyl-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine Step 1: 2-chloro-N-isopropyl-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine The title compound (85 mg) was prepared as a solid in a similar manner to Step 2 of Example 1, except that 4-ethynyl-1-isopropylpyrazole (95 mg, 0.708 mmol) and 2-chloro-5-iodo-N-isopropylpyridin-4-amine (140 mg, 0.472 mmol) were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 303.1 (M+H). + Step 2:N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -Isopropyl-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine The title compound (17 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-chloro-N-isopropyl-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine (110 mg, 0.362 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.61 (s, 1H), 8.44-8.42 (s, 2H), 7.98 (s, 1H), 7.87 (s, 1H), 7.69 (s, 1H), 7.67 (s, 1H), 7.01 (S, 1H), 5.41 (d, 1H), 4.56-4.51 (m, 1H), 3.96-3.93 (m, 1H), 2.84 (t, 1H), 1.61-1.60 (m, 8H), 1.55 (d, 6H), 1.25-1.24 (m, 3H); MS (ESI) m / z = 532.2 (M+H) +

[0863] Example 20:N2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine Step 1: 2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N-isopropylpyridin-4-amine The title compound (115 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 4-ethynyl-1-methylpyrazole (98 mg, 0.708 mmol) and 2-chloro-5-iodo-N-isopropylpyridin-4-amine (140 mg, 0.472 mmol) were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 307.1 (M+H). + Step 2:N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine The title compound (45 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N-isopropylpyridin-4-amine (111 mg, 0.362 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (CDCl3, 600 MHz) δ 8.64 (s, 1H), 8.45 (s, 1H), 8.39 (d, 1H), 8.20 (s, 1H), 8.13 (s, 1H), 7.31 (d, 2H), 7.30 (s, 1H), 7.02 (d, 1H), 4.96 (d, 1H), 4.83 (t, 1H), 4.75 (t, 1H), 4.47 (t, 1H), 4.24 (t, 1H), 3.87-3.84 (m, 1H), 2.85-2.81 (m, 1H), 1.53-1.51 (m, 2H), 1.38 (d, 6H), 1.23-1.20 (m, 2H); MS (ESI) m / z = 536.2 (M+H) +

[0864] Example 21:N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -Isopropyl-5-(pyridin-3-ylethynyl)pyridine-2,4-diamine Step 1: 2-chloro-N-isopropyl-5-(pyridin-3-ylethynyl)pyridin-4-amine The title compound (45 mg) was prepared as a solid in a similar manner to Step 2 of Example 1, except that 3-ethynylpyridine (73 mg, 0.708 mmol) and 2-chloro-5-iodo-N-isopropylpyridin-4-amine (140 mg, 0.472 mmol) were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 272.1 (M+H). + Step 2:N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -Isopropyl-5-(pyridin-3-ylethynyl)pyridine-2,4-diamine The title compound (34 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-chloro-N-isopropyl-5-(pyridin-3-ylethynyl)pyridin-4-amine (98 mg, 0.362 mmol) was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.77 (s, 1H), 8.70 (s, 1H), 8.64 (s, 1H), 8.58 (d, 1H), 8.45 (s, 1H), 8.41 (d, 1H), 8.17 (s, 1H), 7.81 (d, 1H), 7.45 (s, 1H), 7.34-7.32 (m, 1H), 7.00 (d, 1H), 5.00 (d, 1H), 3.92-3.87 (m, 1H), 2.86-2.82 (m, 2H), 1.54-1.52 (m, 2H), 1.39 (d, 6H), 1.22-1.18 (d, 2H); MS (ESI) m / z = 501.2 (M+H) +

[0865] Example 22:N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -Isopropyl-5-(4-methoxybut-1-yn-1-yl)pyridine-2,4-diamine Step 1: 2-chloro-N-isopropyl-5-(4-methoxybut-1-yn-1-yl)pyridin-4-amine The title compound (109 mg) was prepared as a solid in a similar manner to Step 2 of Example 1, except that 4-methoxybut-1-yne (102 mg, 1.214 mmol) and 2-chloro-5-iodo-N-isopropylpyridin-4-amine (240 mg, 0.809 mmol) were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 253.1 (M+H). + Step 2:N 2-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -Isopropyl-5-(4-methoxybut-1-yn-1-yl)pyridine-2,4-diamine The title compound (3 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-chloro-N-isopropyl-5-(4-methoxybut-1-ynyl)pyridin-4-amine (91 mg, 0.362 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.63 (s, 1H), 8.44 (s, 1H), 8.40 (s, 1H), 8.01 (s, 1H), 7.43 (s, 1H), 7.08 (s, 1H), 3.62 (t, 2H), 3.44 (s, 3H), 2.77 (t, 2H), 1.36 (d, 6H), 1.22 (d, 2H), 0.87 (d, 2H); MS (ESI) m / z = 482.2 (M+H) +

[0866] Example 23:N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine Step 1: 2-chloro-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N-isopropylpyridin-4-amine The title compound (165.4 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 1-(2,2-difluoroethyl)-4-ethynyl-pyrazole (139 mg, 0.890 mmol) and 2-chloro-5-iodo-N-isopropylpyridin-4-amine (220 mg, 0.742 mmol) were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 325.1 (M+H) + Step 2:N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine The title compound (39 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-chloro-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N-isopropylpyridin-4-amine (160 mg, 0.493 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (MeOD, 600 MHz) δ 8.75 (s, 1H), 8.46 (s, 1H), 8.40 (d, 1H), 8.06 (s, 1H), 8.00 (s, 1H), 7.76 (s, 1H), 7.24 (s, 1H), 6.21 (t, 1H), 4.63-4.57 (m, 2H), 3.90-3.88 (m, 1H), 3.05-3.03 (m, 1H), 1.46-1.43 (m, 2H), 1.36 (d, 6H), 1.27-1.25 (m, 2H); MS (ESI) m / z = 554.2 (M+H) +

[0867] Example 24: N 4 -(sec-butyl)-N 2-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine Step 1: N-(sec-butyl)-2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine The title compound (132 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that N-(sec-butyl)-2-chloro-5-iodopyridin-4-amine (140 mg, 0.451 mmol) prepared in Preparation 1 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 289.0 (M+H) + Step 2:N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine The title compound (14 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that N-(sec-butyl)-2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine (104 mg, 0.362 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (CDCl3, 600 MHz) δ 8.64 (s, 1H), 8.45 (s, 1H), 8.40 (s, 1H), 8.39 (s, 1H), 8.10 (s, 1H), 7.65 (s, 1H), 7.59 (s, 1H), 7.22 (s, 1H), 7.09 (d, 1H), 4.97 (d, 1H), 3.94 (s, 3H), 3.67-3.62 (m, 1H), 2.85-2.80 (m, 1H), 1.74-1.64 (m, 2H), 1.54-1.51 (m,2H), 1.33 (d, 2H), 1.29-1.23 (m, 2H), 1.22-1.18 (m, 2H), 1.13 (d, 2H), 1.00 (t, 3H); MS (ESI) m / z = 518.2 (M+H) +

[0868] Example 25:N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine Step 1: N-(sec-butyl)-2-chloro-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine The title compound (155 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that N-(sec-butyl)-2-chloro-5-iodopyridin-4-amine (190 mg, 0.612 mmol) prepared in Preparation 1 and 4-ethynyl-1-isopropylpyrazole (123 mg, 0.918 mmol) were used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine and 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 316.1 (M+H) + Step 2:N 4 -(sec-butyl)-N 2-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine The title compound (14 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that N-(sec-butyl)-2-chloro-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine (115 mg, 0.362 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.64 (s, 1H), 8.45 (s, 1H), 8.40 (d, 1H), 8.08 (s, 1H), 7.67 (s, 1H), 7.65 (s, 1H), 7.48-7.45 (m, 1H), 7.24 (s, 1H), 7.11 (s, 1H), 5.00 (d, 1H), 4.55-4.50 (m, 1H), 3.67-3.63 (m, 1H), 2.85-2.80 (m, 1H), 1.75-1.64 (m, 2H), 1.54 (d, 6H), 1.52-1.51 (m, 1H), 1.34 (d, 3H), 1.22-1.18 (m, 2H), 1.01 (t, 3H); MS (ESI) m / z = 546.2 (M+H) +

[0869] Example 26:N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine Step 1: N-(sec-butyl)-2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine The title compound (190 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that N-(sec-butyl)-2-chloro-5-iodopyridin-4-amine (190 mg, 0.612 mmol) prepared in Preparation 1 and 4-ethynyl-1-(2-fluoroethyl)pyrazole (127 mg, 0.918 mmol) were used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine and 4-ethynyl-1-methylpyrazole. MS (ESI) m / z = 320.1 (M+H) + Step 2:N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine The title compound (16 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that N-(sec-butyl)-2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine (116 mg, 0.362 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.64 (s, 1H), 8.55 (s, 1H), 8.45 (s, 1H), 8.40 (d, 1H), 8.10 (s, 1H), 7.71 (s, 2H), 7.08 (s, 1H), 4.98 (d, 1H), 4.83 (t, 1H), 4.75 (t, 1H), 4.47 (t, 1H), 4.42 (t, 1H), 3.68-3.63 (m, 1H), 2.85-2.81 (m, 1H), 1.75-1.65 (m, 2H), 1.54-1.51 (m, 2H), 1.34 (d, 3H), 1.24-1.20 (m, 2H), 1.01 (t, 3H); MS (ESI) m / z = 550.2 (M+H) +

[0870] Example 27: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol Step 1: 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol The title compound (385.4 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-ol (460 mg, 1.359 mmol) prepared in Preparation Example 2 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 317.0 (M+H) + Step 2: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol The title compound (51 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol (200 mg, 0.631 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (CDCl3, 600 MHz) δ 8.68 (s, 1H), 8.45 (s, 1H), 8.41 (d, 1H), 8.24 (s, 1H), 7.65 (s, 1H), 7.63 (s, 1H),7.56 (s, 1H), 6.98 (d, 1H), 4.02-4.00 (m, 1H), 3.93 (s, 3H), 3.88-3.84 (m, 2H), 3.28-3.24 (m, 2H), 2.85-2.82 (m, 1H), 2.18-2.10 (m, 2H), 1.85-1.79 (m, 2H), 1.56-1.53 (m, 2H), 1.25-1.21 (m, 2H); MS (ESI) m / z = 546.2 (M+H) +

[0871] Example 28: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol Step 1: 1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol The title compound (80 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine were replaced with 4-ethynyl-1-(2-fluoroethyl)pyrazole (67 mg, 0.487 mmol) and 1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-ol (150 mg, 0.443 mmol) prepared in Preparation 2. MS (ESI) m / z = 349.2 (M+H) + Step 2: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol The title compound (7 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol (80 mg, 0.229 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.68 (s, 1H), 8.45 (s, 1H), 8.41 (d, 1H), 8.24 (s, 1H), 7.83 (s, 1H), 7.69 (s, 2H), 7.64 (s, 1H), 6.99 (d, 1H), 4.82 (t, 1H), 4.75 (t, 1H), 4.46 (t, 1H), 4.41 (t, 1H), 4.02-4.00 (m, 1H), 3.88-3.84 (m, 2H), 3.28-3.25 (m, 2H), 2.85-2.82 (m, 1H), 2.12-2.10 (m, 2H), 1.85-1.79 (m, 2H), 1.55-1.53 ​​(m, 2H), 1.26-1.21 (m, 2H); MS (ESI) m / z = 560.2 (M+H) +

[0872] Example 29: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol Step 1: (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol The title compound (78 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)methanol (150 mg, 0.425 mmol) prepared in Preparation Example 3 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 2: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol The title compound (5 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol (78 mg, 0.235 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.66 (s, 1H), 8.45 (s, 1H), 8.41 (d, 1H), 8.22 (s, 1H), 7.82 (s, 1H), 7.63 (s, 1H), 7.54 (s, 2H), 7.04 (s, 1H), 4.15 MS (ESI) m / z = 578.2 (M+H) +

[0873] Example 30: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol Step 1: (1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol The title compound (225 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 4-ethynyl-1-(2-fluoroethyl)pyrazole (194 mg, 1.404 mmol) and (1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)methanol (450 mg, 1.276 mmol) prepared in Preparation Example 3 were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 363.1 (M+H) + Step 2: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol The title compound (17 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol (220 mg, 0.606 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (CDCl3, 600 MHz) δ 8.67 (s, 1H), 8.45 (s, 1H), 8.40 (d, 1H), 8.27 (s, 1H), 8.24 (s, 1H), 7.68 (s, 2H), 7.56 (s, 1H), 7.02 (s, 1H), 4.82 (t, 1H), 4.75 (t, 1H), 4.46 (t, 1H), 4.41 (t, 1H), 4.16-4.12 (m, 2H), 2.94 (t, 2H), 2.84-2.82 (m, 1H), 1.87-1.77 (m, 2H), 1.54-1.47 (m, 4H), 1.27-1.20 (m, 2H); MS (ESI) m / z = 592.2 (M+H) +

[0874] Example 31: (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol Step 1: (R)-1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol The title compound (56.6 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (R)-1-(2-chloro-5-iodopyridin-4-yl)pyrrolidin-3-ol (200 mg, 0.616 mmol) prepared in Preparation Example 4 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 317.1 (M+H) + Step 2: (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol The title compound (39 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (R)-1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol (118 mg, 0.390 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (DMSO-d6, 600 MHz) δ 10.08 (s, 1H), 8.66 (s, 1H), 8.44 (s, 1H), 8.41 (d, 1H), 8.03 (s. 1H), 7.99 (s, 1H), 7.63 (s, 1H), 7.35 (s, 2H), 5.06 (s, 1H), 4.40 (s, 1H), 3.88-3.84 (m, 1H), 3.74-3.69 (m, 1H), 3.64-3.62 (m, 1H), 3.52-3.50 (m, 1H), 3.26-3.24 (m, 1H), 2.01 (s, 1H), 2.00 (s, 1H), 1.34-1.32 (m, 2H), 1.27-1.25 (m, 2H); MS (ESI) m / z = 600.2 (M+H) +

[0875] Example 32: (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol Step 1: (R)-1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol The title compound (52 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine were replaced with 4-ethynyl-1-(2-fluoroethyl)pyrazole (112 mg, 0.813 mmol) and (R)-1-(2-chloro-5-iodopyridin-4-yl)pyrrolidin-3-ol (240 mg, 0.739 mmol) prepared in Preparation Example 4. MS (ESI) m / z = 335.1 (M+H) + Step 2: (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol The title compound (10 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (R)-1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol (200 mg, 0.597 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (MeOD, 600 MHz) δ 8.75 (s, 1H), 8.46 (s, 1H), 8.35 (s, 1H), 8.05 (s, 1H), 7.89 (s, 1H), 7.67 (s, 1H), 7.28 (s, 2H), 4.79 (t, 1H), 4.71 (t, 1H), 4.55 (t, 1H), 4.43 (t, 1H), 4.01 (t, 1H), 3.91 (d, 1H), 3.85-3.82 (m, 2H), 3.05-3.03 (m, 1H), 2.19 (s, 1H), 1.59 (s, 2H), 1.45-1.22 (m, 2H), 0.91-0.89 (m, 1H); MS (ESI) m / z = 564.3 (M+H) +

[0876] Example 33: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol Step 1: (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol The title compound (57 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (1-(2-chloro-5-iodopyridin-4-yl)pyrrolidin-3-yl)methanol (200 mg, 0.591 mmol) prepared in Preparation Example 5 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 303.1 (M+H) + Step 2: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol The title compound (23 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol (108 mg, 0.342 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (CDCl3, 600 MHz) δ 8.64 (s, 1H), 8.46 (s, 1H), 8.38 (s, 1H), 8.13 (s, 1H), 7.75 (s, 1H), 7.60 (s, 1H), 7.53 (s, 1H), 6.92 (s, 1H), 3.94 (s, 3H), 3.92-3.85 (m, 1H), 3.84-3.77 (m, 1H), 3.75-3.63 (m, 2H), 2.84-2.82 (m, 1H), 2.59-2.57 (m, 1H), 2.15-2.14 (m, 1H), 1.87-1.84 (m, 2H), 1.55-1.52 (m, 2H), 1.33-1.26 (m, 4H), 1.24-1.22 (m, 2H); MS (ESI) m / z = 546.2 (M+H) +

[0877] Example 34: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol Step 1: (1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol The title compound (144 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine were replaced with 4-ethynyl-1-(2-fluoroethyl)pyrazole (90 mg, 0.650 mmol) and (1-(2-chloro-5-iodopyridin-4-yl)pyrrolidin-3-yl)methanol (200 mg, 0.591 mmol) prepared in Preparation Example 5. MS (ESI) m / z = 349.1 (M+H) + Step 2: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol The title compound (15 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol (143 mg, 0.410 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.64 (s, 1H), 8.46 (s, 1H), 8.37 (d, 1H), 8.13 (s, 1H), 7.87 (s, 1H), 7.66 (s, 1H), 7.31 (s, 1H), 6.90 (s, 1H), 4.81 (t, 1H), 4.74 (t, 1H), 4.44 (t, 1H), 4.40 (t, 1H), 3.95-3.91 (m, 2H), 3.86-3.80 (m, 1H), 3.79-3.75 (m, 1H), 3.69-3.64 (m,2H), 2.84-2.82 (m, 1H), 2.60-2.58 (m, 1H), 2.16-2.13 (m, 1H), 1.87-1.84 (m, 1H), 1.54-1.51 (m, 2H), 1.24-1.20 (m, 2H); MS (ESI) m / z = 578.2 (M+H) +

[0878] Example 35: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol Step 1: 2-(1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol The title compound (184 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 2-(1-(2-chloro-5-iodopyridin-4-yl)azetidin-3-yl)propan-2-ol (261 mg, 0.740 mmol) prepared in Preparation Example 6 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 2: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol The title compound (59 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-(1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol (184 mg, 0.555 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.59 (s, 1H), 8.40 (s, 1H), 8.26 (d, 1H), 7.95 (s, 1H), 7.58 (s, 1H), 7.50 (s, 1H), 7.10 (d, 1H), 6.69 (s, 1H), 4.28 (d, 4H), 3.92 (s, 3H), 2.84-2.80 (m, 2H), 1.54-1.50 (m, 2H), 1.27 (s, 6H), 1.23-1.20 (m, 2H); MS (ESI) m / z = 560.2 (M+H) +

[0879] Example 36: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol Step 1: 2-(1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol The title compound (300 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 4-ethynyl-1-(2-fluoroethyl)pyrazole (129 mg, 0.936 mmol) and 2-(1-(2-chloro-5-iodopyridin-4-yl)azetidin-3-yl)propan-2-ol (261 mg, 0.740 mmol) prepared in Preparation Example 6 were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 363.1 (M+H) + Step 2: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol The title compound (13 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-(1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol (300 mg, 0.827 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (CDCl3, 600 MHz) δ 8.58 (s, 1H), 8.40 (s, 1H), 8.24 (d, 1H), 7.92 (s, 1H), 7.63 (d, 2H), 7.10 (d, 2H), 6.68 (s, 1H), 4.82 (t, 1H), 4.74 MS (ESI) m / z = 592.2 (M+H) +

[0880] Example 37: 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol Step 1: 2-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol The title compound (94 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 2-((2-chloro-5-iodopyridin-4-yl)(methyl)amino)ethan-1-ol (280 mg, 0.896 mmol) prepared in Preparation Example 7 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 291.1 (M+H) + Step 2: 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol The title compound (8 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol (94 mg, 0.322 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.66 (s, 1H), 8.43 (s, 1H), 8.38 (d, 1H), 8.18 (s, 1H), 8.03 (s, 1H), 7.63 (s, 1H), 7.58 (s, 1H), 7.53 (s, 1H), 7.02 MS (ESI) m / z = 520.1 (M+H) +

[0881] Example 38: 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol Step 1: 2-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol The title compound (322 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 4-ethynyl-1-methylpyrazole (136 mg, 0.985 mmol) and 2-((2-chloro-5-iodopyridin-4-yl)(methyl)amino)ethan-1-ol (280 mg, 0.896 mmol) prepared in Preparation Example 7 were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 323.1 (M+H) + Step 2: 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol The title compound (20 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 2-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol (322 mg, 0.998 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 600 MHz) δ 8.67 (s, 1H), 8.44 (s, 1H), 8.40 (d, 1H), 8.20 (s, 1H), 7.71-7.69 (m, 3H), 7.40 (s, 1H), 7.06 (d, 1H), 4.82 (t, 1H), 4.74 MS (ESI) m / z = 552.2 (M+H) +

[0882] Example 39: 3-((2-((2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl)amino)-5-(2-(1-methylpyrazol-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propan-1-ol Step 1: 3-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-2,2-dimethylpropan-1-ol The title compound (109 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 3-((2-chloro-5-iodopyridin-4-yl)amino)-2,2-dimethylpropan-1-ol (150 mg, 0.440 mmol) prepared in Preparation Example 8 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 319.1 (M+H) + Step 2: 3-((2-((2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl)amino)-5-(2-(1-methylpyrazol-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propan-1-ol The title compound (24 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 3-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-2,2-dimethylpropan-1-ol (100 mg, 0.314 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (CDCl3, 400 MHz) δ 8.63 (s, 1H), 8.44 (s, 1H), 8.33 (d, 1H), 7.59 (s, 1H), 7.54 (s, 1H), 7.18 (s, 1H), 7.03 (d, 1H), 3.87 (s, 3H), 3.53 (s, 2H), 3.21 (d, 2H), 2.82-2.78 (m, 1H), 1.51-1.47 (m, 2H), 1.22-1.15 (m, 2H), 1.04 (s, 6H); MS (ESI) m / z = 548.2 (M+H) +

[0883] Example 40: 3-((2-((2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl)amino)-5-(2-(1-(2-fluoroethyl)pyrazol-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propan-1-ol Step 1: 3-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-2,2-dimethylpropan-1-ol The title compound (139 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 4-ethynyl-1-(2-fluoroethyl)pyrazole (67 mg, 0.484 mmol) and 3-((2-chloro-5-iodopyridin-4-yl)amino)-2,2-dimethylpropan-1-ol (150 mg, 0.440 mmol) prepared in Preparation Example 8 were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 351.1 (M+H) + Step 2: 3-((2-((2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl)amino)-5-(2-(1-(2-fluoroethyl)pyrazol-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propan-1-ol The title compound (6 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that 3-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-2,2-dimethylpropan-1-ol (130 mg, 0.371 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 400 MHz) δ 8.66 (s, 1H), 8.48 (s, 1H), 8.39 (d, 1H), 8.09 (s, 1H), 7.84 (s, 1H), 7.70 (s, 2H), 7.16-7.12 (m, 2H), 5.92-5.90 (m, 2H), 4.83 (t, 1H), 4.72 (t, 1H), 4.46 (t, 1H), 4.40 (t, 1H), 3.56 (s, 2H), 3.26 (d, 2H), 2.85-2.81 (m, 2H), 1.55-1.51 (m, 2H),1.34-1.31 (m, 2H), 1.18 (s, 6H); MS (ESI) m / z = 580.2 (M+H) +

[0884] Example 41: (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol Step 1: (1s,4s)-4-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (206 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (1s,4s)-4-((2-chloro-5-iodopyridin-4-yl)amino)cyclohexan-1-ol (250 mg, 0.709 mmol) prepared in Preparation Example 9 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 2: (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (72 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1s,4s)-4-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol (200 mg, 0.605 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (DMSO-d6, 600 MHz) δ 10.06 (s, 1H), 8.64 (s, 1H), 8.44 (s, 1H), 8.42 (d, 1H), 8.07 (s, 1H), 8.04 (s, 1H), 7.70 (s, 1H), 7.49 (s, 1H), 7.23 (s, 1H), 5.40 (d, 1H), 4.60 (d, 1H), 3.85 (s, 3H), 3.69 (s, 1H), 3.26-3.22 (m, 1H), 1.81-1.69 (m, 4H), 1.61-1.53 ​​(m, 4H), 1.35-1.32 (m, 2H), 1.30-1.21 (m, 2H); MS (ESI) m / z = 560.2 (M+H) +

[0885] Example 42: (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol Step 1: (1s,4s)-4-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (208 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 4-ethynyl-1-(2-fluoroethyl)pyrazole (108 mg, 0.780 mmol) and (1s,4s)-4-((2-chloro-5-iodopyridin-4-yl)amino)cyclohexan-1-ol (250 mg, 0.709 mmol) prepared in Preparation Example 9 were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 363.0 (M+H) + Step 2: (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (86 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1s,4s)-4-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol (200 mg, 0.551 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (DMSO-d6, 600 MHz) δ 10.06 (s, 1H), 8.64 (s, 1H), 8.44 (s, 1H), 8.43 (d, 1H), 8.15 (s, 1H), 8.05 (s, 1H), 7.77 (s, 1H), 7.50 (s, 1H), 7.23 (s, 1H), 5.44 (d, 1H), 4.81 (t, 1H), 4.73 (t, 1H), 4.59 (d, 1H), 4.48 (t, 1H), 4.43 (t, 1H), 3.70 (s, 1H), 3.26-3.22 (m, 1H), 1.82-1.70 (m, 4H), 1.60-1.54 (m, 4H), 1.35-1.32 (m, 2H), 1.26-1.20 (m, 2H); MS (ESI) m / z = 592.2 (M+H) +

[0886] Example 43: (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol Step 1: (1S,3S)-3-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (155 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (1S,3S)-3-((2-chloro-5-iodopyridin-4-yl)amino)cyclohexan-1-ol (200 mg, 0.567 mmol) prepared in Preparation 10 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 2: (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (75 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1S,3S)-3-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol (190 mg, 0.574 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (DMSO-d6, 600 MHz) δ 10.02 (s, 1H), 8.63 (s, 1H), 8.44 (s, 1H), 8.41 (d, 1H), 8.04 (s, 1H), 7.99 (s, 1H), 7.66 (s, 1H), 7.44 (s, 1H), 7.21 (s, 1H), 6.51 (s, 1H), 5.02 (d, 1H), 3.85 (s, 3H), 3.81 (s, 1H), 3.68 (s, 1H), 3.27-3.22 (m, 1H), 2.00 (d, 1H), 1.76-1.60 (m, 5H), 1.45 (s, 1H), 1.35-1.30 (m, 2H), 1.26-1.21 (m, 2H); MS (ESI) m / z = 560.2 (M+H) +

[0887] Example 44: (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol Step 1: (1S,3S)-3-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (173 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine were replaced with 4-ethynyl-1-(2-fluoroethyl)pyrazole (86 mg, 0.624 mmol) and (1S,3S)-3-((2-chloro-5-iodopyridin-4-yl)amino)cyclohexan-1-ol (200 mg, 0.567 mmol) prepared in Preparation 10. MS (ESI) m / z = 363.2 (M+H) + Step 2: (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (26 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1S,3S)-3-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol (220 mg, 0.606 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (DMSO-d6, 600 MHz) δ 10.04 (s, 1H), 8.63 (s, 1H), 8.44 (s, 1H), 8.42 (d, 1H), 8.09 (s, 1H), 8.02 (s, 1H), 7.75 (s, 1H), 7.47 (s, 1H), 7.20 (s, 1H), 6.50 (s, 1H), 5.03 (s, 1H), 4.81 (t, 1H), 4.73 (t, 1H), 4.47 (s, 1H), 4.43 (s, 1H), 3.80 (s, 1H), 3.67 (s, 1H), 3.26-3.22 (m, 1H), 2.01 (d, 1H), 1.75-1.59 (d, 5H), 1.43 (s, 1H), 1.35-1.30 (m, 2H), 1.27-1.21 (m, 2H); MS (ESI) m / z = 592.2 (M+H) +

[0888] Example 45: (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol Step 1: (1S,3R)-3-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (193 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (1S,3R)-3-((2-chloro-5-iodopyridin-4-yl)amino)cyclohexan-1-ol (270 mg, 0.766 mmol) prepared in Preparation Example 11 was used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 2: (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (38 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1S,3R)-3-((2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol (150 mg, 0.453 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (DMSO-d6, 600 MHz) δ 10.04 (s, 1H), 8.63 (s, 1H), 8.44 (s, 1H), 8.43 (d, 1H), 8.05 (s, 1H), 8.04 (s, 1H), 7.69 (s, 1H), 7.63 (s, 1H) 7.06 (s, 1H), 5.36 (d, 1H), 4.61 (d, 1H), 3.89 (s, 1H), 3.85 (s, 3H), 3.27-3.23 (m, 1H), 1.87-1.70 (m, 4H), 1.49-1.43 (m, 4H), 1.36-1.30 (m, 2H), 1.25-1.20 (m, 2H); MS (ESI) m / z = 560.2 (M+H) +

[0889] Example 46: (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol Step 1: (1S,3R)-3-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (221 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine were replaced with 4-ethynyl-1-(2-fluoroethyl)pyrazole (116 mg, 0.842 mmol) and (1S,3R)-3-((2-chloro-5-iodopyridin-4-yl)amino)cyclohexan-1-ol (270 mg, 0.766 mmol) prepared in Preparation 11. MS (ESI) m / z = 363.1 (M+H) + Step 2: (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol The title compound (20 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1S,3R)-3-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol (170 mg, 0.469 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1H-NMR (DMSO-d6, 600 MHz) δ 10.06 (s, 1H), 8.64 (s, 1H), 8.44 (s, 1H), 8.43 (s, 1H), 8.15 (s, 1H), 8.05 (s, 1H), 7.77 (s, 1H), 7.63 (s, 1H), 7.04 (s, 1H), 5.42 (s, 1H), 4.81 (t, 1H), 4.73 (t, 1H), 4.60 (s, 1H), 4.48 (t, 1H), 4.43 (s, 1H), 3.91 (s, 1H), 3.85 (s, 1H), 3.27-3.23 (m, 2H), 1.88-1.70 (m, 5H), 1.49-1.43 (m, 3H), 1.35-1.33 (m, 2H), 1.26-1.21 (m, 2H); MS (ESI) m / z = 592.2 (M+H) +

[0890] Example 47: (1-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol Step 1: (1-(2-chloro-5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol The title compound (103 mg) was prepared as a solid in the same manner as in Step 2 of Example 1, except that (1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperidin-4-yl)methanol (110 mg, 0.300 mmol) and 1-cyclopropyl-4-ethynylpyrazole (48 mg, 0.360 mmol) prepared in Preparation 12 were used instead of 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine and 4-ethynyl-1-methylpyrazole, respectively. MS (ESI) m / z = 371.0 (M+H) + Step 2: (1-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol The title compound (10 mg) was prepared as a solid in the same manner as in Step 3 of Example 1, except that (1-(2-chloro-5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol (98 mg, 0.264 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperazine. 1 H-NMR (CDCl3, 400 MHz) δ 8.65 (s, 1H), 8.44 (s, 1H), 8.40 (s, 1H), 8.38 (s, 1H), 8.20 (s, 1H), 7.62-7.69 (m, 3H), 6.97 (d, 1H), 3.67-3.65 (m, 2H), 3.64-3.59 (m, 1H), 3.50 (s, 2H), 3.42-3.36 (m, 2H), 2.85-2.81 (m, 1H), 2.04-2.00 (m, 2H), 1.80-1.74 (m, 3H), 1.58-1.50 (m, 4H), 1.35-1.20 (m, 5H), 1.17-1.11 (m, 3H), 1.10-1.06 (m, 5H); MS (ESI) m / z = 600.2 (M+H) +

[0891] Example 48: (1-(5-((1-(cyclopropylmethyl)-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyr...

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof: 【Chemical 1】 Wherein, R １ is -H; -Si(C １－６ alkyl) 3 ; OH, halogen, C １－3 alkoxy, C ３－６ cycloalkyl, -NHC １－６ alkyl, -NHC １－6 haloalkyl, -N(C １－６ alkyl) ２ , -N(C １－６ haloalkyl) ２ , -NHCOC １－６ alkyl, -NHCOC １－６ haloalkyl, -NHCOC ３－６ cycloalkyl, -NHCO-4- to 7-membered heterocyclyl, -CO-4- to 7-membered heterocyclyl, and C １－６ alkyl, halogen, OH, and oxo, optionally or independently substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of C １－６ alkyl; C ２－５ Alkenyl; -C(O)NHC １－６ alkyl; -C(O)N(C １－６ alkyl) 2 ; -C(O)-4- to 7-membered heterocyclyl; -NHC optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen １－６ alkyl; -N(C １－６ alkyl) optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen ２ ; and -A-(R １Ａ ) ｍ selected from the group consisting of, A is C ３－６ Cycloalkyl; C ６－１０ Selected from the group consisting of aryl; 4- to 8-membered heterocyclyl; and 5- to 10-membered heteroaryl, R １Ａ is H; OH; NH ２ ; Halogen; OH, halogen, C ３－６ cycloalkyl, -NHC １－６ alkyl, -NHC ３－６ cycloalkyl, -N(C １－６ alkyl) 2 , -C(O)N(C １－６ alkyl) ２ , -C(O)N-4- to 7-membered heterocyclyl, -NHOC(O)C １－６ alkyl, and optionally substituted with one or more substituents selected from the group consisting of halogen, C １－６ alkyl, C １－６ haloalkyl, C １－６ hydroxyalkyl, and -C(O)C １－６ alkyl, and optionally substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of １－６ alkyl; OH, halogen, and -N(C １－６ alkyl) 2 optionally substituted with one or more substituents selected from the group consisting of C ３－６ cycloalkyl; -C(O)C optionally substituted with one or more substituents selected from the group consisting of OH and halogen １－６ alkyl; -C(O)N(C １－６ alkyl) ２ ; -C(O)-4- to 7-membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of OH and halogen; -NHC optionally substituted with a 4- to 7-membered heterocycle １－６ alkyl; -N(C １－６ alkyl) 2 ; -S(O) ２ C １－6 Alkyl; -S(O) ２ C ３－６ Cycloalkyl; Oxo; and Halogen, -N(C １－６ alkyl) ２ optionally substituted with C １－６ alkyl, C ３－６ cycloalkyl, C １－６ haloalkyl, -C(O)C １－６ alkyl, and a 4- to 11-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of a 4- to 7-membered heterocyclyl Independently selected from the group consisting of, m is an integer from 0 to 2, R ２ is optionally substituted with one or more OHs -N(C １－６ alkyl) ２ ; OH, halogen, C ３－６ cycloalkyl, C １－３ alkoxy, -NHC １－６ alkyl, or -N(C １－６ alkyl) ２ optionally substituted -XC １－６ alkyl; and -X(CH ２ ) ｎ -B-(R ２Ａ ) ｏ selected from the group consisting of, X is a bond, -NH-, or -O-, n is an integer from 0 to 1, o is an integer from 0 to 3, B is C ３－７ Cycloalkyl; C ６－１０ Selected from the group consisting of aryl; 4- to 12-membered heterocyclyl; and 5- to 6-membered heteroaryl, R ２Ａ is H; OH; Halogen; OH, halogen, -NHC １－６ alkyl, -NHC １－６ haloalkyl, -N(C １－６ alkyl) ２ , a 4- to 7-membered heterocyclyl, and C １－３ alkyl optionally or independently substituted with one or more substituents selected from the group consisting of alkoxy, C １－６ alkyl; C optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen ３－６ cycloalkyl; C optionally or independently substituted with one or more halogens １－３ alkoxy; -C(O)NHC １－６ alkyl; -C(O)N(C １－６ alkyl) ２ ; -C(O)NHC ３－６ cycloalkyl; OH, halogen, C ３－６ Cycloalkyl, C １－３ Alkoxy, -NHC １－６ Alkyl, -N(C １－６ Alkyl) ２ , and -NHC optionally or independently substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclyl １－６ Alkyl; -NHC optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen ３－６ cycloalkyl; Optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen -N(C １－６ alkyl) ２ ; -NHC(O)C １－６ alkyl; -NHC(O)C ３－６ cycloalkyl; -NHS(O) ２ C １－６ alkyl; -S(O) ２ C １－６ alkyl; Halogen and C １－６ A 4- to 7-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl; =O; and C(O)C １－６ Alkyl Independently selected from the group consisting of, R ３ is Y - Q - (R ３Ａ ) ｐ and Y is -NH- or a bond, p is an integer from 0 to 2, Q is selected from the group consisting of 4- to 7-membered heterocyclyl; C ６－１０ aryl; and 5- to 6-membered heteroaryl, R ３Ａ is C optionally substituted with one or more substituents selected from the group consisting of H; halogen; halogen and C ３－６ alkyl; C １－６ cycloalkyl; 4- to 7-membered heterocyclyl; -S(O) optionally substituted with 1 to 3 halogens ３－６ C ２ alkyl; -S(O) optionally substituted with one or more halogens １－６ C ２ cycloalkyl; and -S(O) ３－６ N(C ２ alkyl)2, independently selected from the group consisting of １－６ ​ R ４ is selected from the group consisting of H, halogen, and C １－６ alkyl.

2. R １ is -H; -Si(C １－６ alkyl) ３ ; OH, halogen, C １－３ alkoxy, -NHC(O)C １－６ haloalkyl, -NHC(O)-4- to 7-membered heterocyclyl, -C(O)-4- to 7-membered heterocyclyl, and 4- to 7-membered heterocyclyl optionally or independently substituted with oxo, optionally or independently substituted with one or more substituents selected from the group consisting of １－６ alkyl; C ２－５ alkenyl; and -A-(R １Ａ ) ｍ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of

3. The compound or a pharmaceutically acceptable salt thereof according to claim 2, wherein the 4- to 7-membered heterocyclyl is selected from the group consisting of morpholinyl, pyrrolidinyl, 1,1-dioxo-1,4-thiazinaninyl, and oxetanyl.

4. A is C ３－６ Cycloalkyl, phenyl, pyrazolyl, pyridinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, triazolyl, thiazolyl, pyrazinyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, thienyl, pyrimidinyl, tetrahydrofuranyl, imidazolyl, pyrrolyl, pyrrolo[3,2-c]pyridinyl, oxetanyl, 7-oxabicyclo The compound or a pharmaceutically acceptable salt thereof according to claim 1, selected from the group consisting of [2.

2. .1]heptanyl and 1,1-dioxo-thiolanyl.

5. R １Ａ is H; OH; NH ２ ; Halogen; OH, halogen, C ３－６ cycloalkyl, -N(C １－６ alkyl) ２ , -C(O)N(C １－６ alkyl) ２ , and C optionally substituted with one or more substituents selected from the group consisting of halogen and C １－６ alkyl; optionally substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of １－６ alkyl; C optionally substituted with one or more halogens ３－６ cycloalkyl; -C(O)C optionally substituted with one or more halogens １－６ alkyl; -C(O)N(C １－６ alkyl) ２ ; -C(O)-4- to 7-membered heterocyclyl optionally substituted with one or more OH; -NHC optionally substituted with a 4- to 7-membered heterocycle １－６ alkyl; -S(O) ２ C １－６ alkyl; -S(O) ２ C ３－６ Cycloalkyl; and C １－６ alkyl and -C(O)C １－６ a 4- to 11-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl The compound or a pharmaceutically acceptable salt thereof according to claim 1, selected from the group consisting of.

6. The compound or a pharmaceutically acceptable salt thereof according to claim 5, wherein the 4- to 7-membered heterocyclyl or 4- to 11-membered heterocyclyl is selected from the group consisting of tetrahydropyranyl, piperidinyl, azetidinyl, morpholinyl, piperazinyl, dioxanyl, tetrahydrofuranyl, and oxetanyl.

7. R ２ which is optionally substituted with one or more OHs -N(C １－６ alkyl) ２ ; -XC １－６ alkyl optionally substituted with OH; and -X(CH ２ ) ｎ -B-(R ２Ａ ) ｏ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of

8. B is C ３－６ The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein B is selected from the group consisting of cycloalkyl; phenyl; piperazinyl, piperidinyl, 4-oxopiperidinyl, azaspiro[3.5]nonanyl, pyrrolidinyl, azetidinyl, azepanyl, 2,8-diazaspiro[4.5]decanonyl, 2,8-diazaspiro[4.5]decanyl, 2,7-diazaspiro[3.5]nonanyl, pyrazolyl, 1-oxa-8-azaspiro[4.5]decanonyl, 1-oxa-7-azaspiro[3.5]nonanyl, 3,9-diazaspiro[5.5]undecanyl, 3-azabicyclo[3.1.0]hexanyl, 8-azabicyclo[3.2.1]octanyl, and 1-azaspiro[4.5]decanonyl.

9. R ２Ａ is H; OH; Halogen; OH, halogen, -NHC １－６ alkyl, -NHC １－６ haloalkyl, and -N(C １－６ alkyl) ２ optionally or independently substituted with one or more substituents selected from the group consisting of C １－６ alkyl; C optionally or independently substituted by one or more OHs ３－６ cycloalkyl; C optionally or independently substituted with one or more halogens １－３ alkoxy; OH, halogen, C ３－６ cycloalkyl, C １－３ alkoxy, and -N(C １－６ alkyl) ２ optionally or independently substituted with one or more substituents selected from the group consisting of -NHC １－６ alkyl; -NHS(O) ２ C １－６ alkyl; -S(O) ２ C １－６ alkyl; Halogen and C １－６ A 4- to 7-membered heterocyclyl optionally or independently substituted with one or more substituents selected from the group consisting of alkyl; =O; and C(O)C １－６ Alkyl Independently selected from the group consisting of, the compound or a pharmaceutically acceptable salt thereof according to claim 1.

10. The compound or a pharmaceutically acceptable salt thereof according to claim 9, wherein the 4- to 7-membered heterocyclyl is piperazinyl or azetidinyl.

11. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein Q is selected from the group consisting of pyrazolyl, pyridinyl, phenyl, and piperazinyl.

12. R3A is halogen; C optionally substituted with one or more halogens １－６ alkyl; -S(O) ２ C １－６ alkyl; -S(O) ２ C ３－６ cycloalkyl; and -S(O) ２ N(C １－６ alkyl)2, the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

13. R ４ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R is H.

14. (1) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-methylpiperazin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (2) N 4 -Cyclohexyl-N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (3) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(ethylsulfonyl)piperazin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (4) (R)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)butan-1-ol; (5) (S)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-2-methylbutan-2-ol; (6) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol; (7) 1-(2-((2-(1-(Cyclopropylsulfonyl)-yrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-one; (8) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoropiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (9) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol; (10) 1-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol; (11) 2-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)propan-2-ol; (12) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (13) 7-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol; (14) 2-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol; (15) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-methoxypiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (16) 2-(4-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperazin-1-yl)ethan-1-ol; (17) 2-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethanol; (18) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (19) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (20) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -isopropylpyridine-2,4-diamine; (21) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-(pyridin-3-ylethynyl)pyridine-2,4-diamine; (22) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-(4-methoxybut-1-yn-1-yl)pyridine-2,4-diamine; (23) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -isopropylpyridine-2,4-diamine; (24) N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (25) N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (26) N 4 -(sec-Butyl)-N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (27) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol; (28) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol; (29) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol; (30) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol; (31) (R)-1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol; (32) (R)-1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-ol; (33) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol; (34) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)pyrrolidin-3-yl)methanol; (35) 2-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol; (36) 2-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azetidin-3-yl)propan-2-ol; (37) 2-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol; (38) 2-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)(methyl)amino)ethan-1-ol; (39) 3-((2-((2-(1-Cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl)amino)-5-(2-(1-methylpyrazol-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propan-1-ol; (40) 3-((2-((2-(1-Cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl)amino)-5-(2-(1-(2-fluoroethyl)pyrazol-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propan-1-ol; (41) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (42) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (43) (1S,3S)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (44) (1S,3S)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (45) (1S,3R)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (46) (1S,3R)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (47) (1-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (48) (1-(5-((1-(Cyclopropylmethyl)-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (49) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (50) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -(4-((Dimethylamino)methyl)benzyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (51) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -(4-((Dimethylamino)methyl)benzyl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (52) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -(4-((Dimethylamino)methyl)benzyl)pyridine-2,4-diamine; (53) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -(((1r,4r)-4-((Dimethylamino)methyl)cyclohexyl)methyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (54) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-isopropoxy-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (55) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-isopropoxypyridin-2-yl)pyrimidin-4-amine; (56) N-(4-(sec-butoxy)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (57) N-(4-(sec-butoxy)-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (58) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (59) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((1-isopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (60) N-(5-((1-Cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (61) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (62) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-(pyridin-3-ylethynyl)pyridin-2-yl)pyrimidin-4-amine; (63) N-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanesulfonamide; (64) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(isopropylamino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (65) 2-(z1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-(trifluoromethyl)piperidin-zy1)pyridin-2-yl)pyrimidin-4-amine; (66) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoro-4-(trifluoromethyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (67) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-(trifluoromethoxy)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (68) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3,3-difluoropiperidin-4-ol; (69) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3,3-dimethylpiperidin-4-ol; (70) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-fluoropiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (71) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(3-(trifluoromethyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (72) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-(fluoromethyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (73) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol; (74) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -(3-Fluorocyclohexyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (75) (1R,3S)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (76) (1R,3R)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (77) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azepan-4-ol; (78) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)azepan-4-yl)methanol; (79) 8-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decan-1-one; (80) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((2-Fluoroethyl)amino)cyclohexyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (81) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol; (82) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol; (83) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol; (84) 2-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol; (85) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (86) 1-(5-((5-Cyclopropyl-1-methyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-ol; (87) 2-(1-(5-((5-Cyclopropyl-1-methyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-yl)ethan-1-ol; (88) (1s,4s)-4-((5-((5-Cyclopropyl-1-methyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexan-1-ol; (89) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol; (90) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol; (91) 2-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol; (92) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)- \ 5-((1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (93) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-one; (94) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (95) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (96) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol; (97) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoropiperidin-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (98) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-methoxypiperidin-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (99) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol; (100) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol; (101) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (102) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (103) (1S,3S)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (104) 7-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol; (105) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol; (106) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (107) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (108) 1-(5-((1-(1-acetylpiperidin-4-yl)-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-one; (109) 1-(4-(4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1S,4S)-4-hydroxycyclohexyl)amino)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; (110) 1-(4-(4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; (111) 1-(4-(4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-fluoro-4-(hydroxymethyl)piperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; (112) 1-(4-(4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-fluoropiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; (113) 1-(4-(4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-methoxypiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; (114) 1-(4-(4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; (115) 1-(4-(4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(3-(hydroxymethyl)piperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; (116) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol- ​ ​ (119) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (120) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (121) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol; (122) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)methanol; (123) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (124) N-(4-(4-((Cyclopropylmethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (125) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(isopentylamino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (126) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2,2-difluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (127) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-((3,3,3-trifluoropropyl)amino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (128) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(3,3-difluoroazetidin-1-yl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (129) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (130) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-(methylamino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (131) 2-((1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)amino)ethan-1-ol; (132) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-methoxyethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (133) N 1 -(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-N 2 ,N 2 -dimethyl ethane-1,2-diamine; (134) N 1 -(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-N 2 ,N 2 , 2,2-dimethylpropane-1,2-diamine; (135) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-((2,2,2-trifluoroethyl)amino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (136) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidin-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (137) 2-((1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)amino)ethan-1-ol; (138) N 1 -(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-N 2 ,N 2 -dimethyl ethane-1,2-diamine; (139) 1-(4-(4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-((2-(dimethylamino)ethyl)amino)piperidin-1-yl)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethan-1-one; (140) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-3-yl)ethynyl)-4-(4-(methylamino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (141) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (142) N 1 -(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-3-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-N 2 ,N 2 -dimethyl ethane-1,2-diamine; (143) N 1 -(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)-N 2 ,N 2 -dimethyl ethane-1,2-diamine; (144) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)ethynyl)-4-(4-((2-fluoroethyl)amino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (145) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)-4-(4-((2-fluoroethyl)amino)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (146) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-methyl-4-((methylamino)methyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (147) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (148) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (149) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (150) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (151) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(2,2-difluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (152) 7-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol; (153) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(4-(2-(methylamino)ethyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (154) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(2,8-diazaspiro[4.5]dec-2-yl)pyridin-2-yl)pyrimidin-4-amine; (155) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(2,7-diazaspiro[3.5]non-2-yl)pyridin-2-yl)pyrimidin-4-amine; (156) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(2,8-diazaspiro[4.5]dec-8-yl)pyridin-2-yl)pyrimidin-4-amine; (157) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (158) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol; (159) (1R,3S)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (160) (1S,3R)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (161) (1S,3S)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (162) 2-((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexyl)propan-2-ol; (163) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (164) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (165) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(3-morpholinoprop-1-yn-1-yl)pyridin-4-yl)amino)cyclohexan-1-ol; (166) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(3-morpholinoprop-1-yn-1-yl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol; (167) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1,2,4-triazol-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (168) (1S,3R)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-ethylthiazol-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (169) (1S,3R)-3-((5-((3-aminophenyl)ethynyl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexan-1-ol; (170) (1S,3R)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-methylpyrazin-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (171) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(3-(pyrrolidin-1-yl)prop-1-yn-1-yl)pyridin-4-yl)amino)cyclohexan-1-ol; (172) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((2-morpholinoethyl)amino)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (173) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-((2-morpholinoethyl)amino)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (174) 1-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridin-3-yl)ethynyl)cyclohexan-1-ol; (175) 1-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)cyclohexan-1-ol; (176) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-hydroxycyclopentyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (177) 1-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)cyclopentan-1-ol; (178) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (179) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (180) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylpyrrolidin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (181) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylpyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (182) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylpiperidin-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (183) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-methyltetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (184) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyridin-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (185) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyridin-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (186) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-(morpholinomethyl)pyridin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (187) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-(Morpholinomethyl)pyridin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (188) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(Morpholinomethyl)thiazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (189) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(Morpholinomethyl)thiazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (190) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(Morpholinomethyl)thiophen-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (191) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(Morpholinomethyl)thiophen-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (192) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(Morpholinomethyl)thiazol-5-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (193) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(Morpholinomethyl)pyrimidin-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (194) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(Morpholinomethyl)pyrimidin-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (195) 4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(Hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)tetrahydro-2H-pyran-4-ol; (196) 4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-Hydroxycyclohexyl)amino)pyridin-3-yl)ethynyl)tetrahydro-2H-pyran-4-ol; (197) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((Tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (198) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((Tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (199) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((2-methylthiazol-4-yl)ethynyl)pyridine-2,4-diamine; (200) N 2- (2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((2-(fluoromethyl)thiazol-4-yl)ethynyl)-N 4 -isopropylpyridine-2,4-diamine; (201) 4-(3-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(Isopropylamino)pyridin-3-yl)prop-2-yn-1-yl)thiomorpholine 1,1-dioxide; (202) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-(3-morpholinoprop-1-in-1-yl)pyridine-2,4-diamine; (203) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-(3-(pyrrolidin-1-yl)prop-1-yn-1-yl)pyridine-2,4-diamine; (204) 4-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(Isopropylamino)pyridin-3-yl)-2-methylbut-3-yn-2-ol; (205) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((2-cyclopropylthiazol-4-yl)ethynyl)-N 4 -isopropylpyridine-2,4-diamine; (206) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -isopropyl-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridine-2,4-diamine; (207) N-(5-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(Isopropylamino)pyridin-3-yl)penta-4-yn-1-yl)morpholine-4-carboxamide; (208) 6-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(isopropylamino)pyridin-3-yl)-1-morpholinohex-5-yn-1-one; (209) N-(6-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(isopropylamino)pyridin-3-yl)hex-5-yn-1-yl)morpholine-4-carboxamide; (210) 7-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(isopropylamino)pyridin-3-yl)-1-morpholinohept-6-yn-1-one; (211) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methylthiazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol; (212) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(fluoromethyl)thiazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol; (213) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-imidazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-ol; (214) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-1,2,4-triazol-3-yl)ethynyl)pyridin-4-yl)piperidin-4-ol; (215) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-morpholinopyridin-3-yl)ethynyl)pyridin-4-yl)piperidin-4-ol; (216) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-imidazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (217) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(thiophen-3-ylethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (218) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (219) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-morpholinoethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (220) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol; (221) 2-(4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1S,4S)-4-hydroxy-4-methylcyclohexyl)amino)pyridin-3-yl)ethynyl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide; (222) (1S,3S)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methylthiazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclopentan-1-ol; (223) (1S,3R)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-imidazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclopentan-1-ol; (224) 3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-imidazol-4-yl)ethynyl)pyridin-4-yl)amino)-2,2-dimethylpropan-1-ol; (225) (1S,3S)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(thiophen-3-ylethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (226) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-5-(thiophen-3-ylethynyl)pyridin-2-yl)pyrimidin-4-amine; (227) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-morpholinopyridin-3-yl)ethynyl)pyridin-4-yl)piperidin-3-ol; (228) (S)-1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(thiophen-3-ylethynyl)pyridin-4-yl)piperidin-3-ol; (229) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(thiophen-3-ylethynyl)pyridin-4-yl)-3,3-dimethylpiperidin-4-ol; (230) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(3-methyl-3-morpholinobut-1-yn-1-yl)pyridin-4-yl)amino)cyclohexan-1-ol; (231) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((Tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (232) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-Morpholinoethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (233) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(1-Methyl-1H-pyrazol-4-yl)-5-((1-Methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (234) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2-Fluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-(1-Methyl-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine; (235) N-(4-(1-Cyclopropyl-1H-pyrazol-4-yl)-5-((1-Methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (236) N-(4-(1-Cyclopropyl-1H-pyrazol-4-yl)-5-((1-Isopropyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (237) N-(4-(1-Cyclopropyl-1H-pyrazol-4-yl)-5-((1-(2-Fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (238) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((Dimethylamino)methyl)cyclohexyl)methoxy)-5-((2-methylthiazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (239) 4-(3-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1r,4r)-4-((Dimethylamino)methyl)cyclohexyl)methoxy)pyridin-3-yl)prop-2-yn-1-yl)thiomorpholine 1,1-dioxide; (240) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(((1r,4r)-4-((Dimethylamino)methyl)cyclohexyl)methoxy)-5-(3-(pyrrolidin-1-yl)prop-1-yn-1-yl)pyridin-2-yl)pyrimidin-4-amine; (241) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-3-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (242) (1-(5-((1-((1,4-dioxan-2-yl)methyl)-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (243) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-((tetrahydrofuran-3-yl)methyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (244) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (245) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(oxetan-3-yl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (246) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((trimethylsilyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (247) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-ethynylpyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (248) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-((3,3-difluoroazetidin-1-yl)methyl)-1-(2,2-difluoroethyl)-1H-pyrrol-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (249) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (250) (1-(5-(Cyclopropylethynyl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (251) (1-(5-(Cyclopentylethynyl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (252) (1-(5-(Cyclohexylethynyl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (253) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (254) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((dimethylamino)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (255) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-((dimethylamino)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (256) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(phenylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (257) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-fluorophenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (258) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-4-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (259) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-2-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (260) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-3-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (261) (3 - ((6 - ((2 - (1 - (cyclopropylsulfonyl)-1H - pyrazol - 4 - yl)pyrimidin - 4 - yl)amino)-4-(4 - (hydroxymethyl)-4 - methylpiperidin - 1 - yl)pyridin - 3 - yl)ethynyl)phenyl)(morpholino)methanone; (262) 4 - ((6 - ((2 - (1 - (cyclopropylsulfonyl)-1H - pyrazol - 4 - yl)pyrimidin - 4 - yl)amino)-4-(4 - (hydroxymethyl)-4 - methylpiperidin - 1 - yl)pyridin - 3 - yl)ethynyl)-N,N - dimethylbenzamide; (263) (4 - ((6 - ((2 - (1 - (cyclopropylsulfonyl)-1H - pyrazol - 4 - yl)pyrimidin - 4 - yl)amino)-4-(4 - (hydroxymethyl)-4 - methylpiperidin - 1 - yl)pyridin - 3 - yl)ethynyl)phenyl)(morpholino)methanone; (264) 6 - ((6 - ((2 - (1 - (cyclopropylsulfonyl)-1H - pyrazol - 4 - yl)pyrimidin - 4 - yl)amino)-4-(4 - (hydroxymethyl)-4 - methylpiperidin - 1 - yl)pyridin - 3 - yl)ethynyl)-N,N - dimethylpicolinamide; (265) (6 - ((6 - ((2 - (1 - (cyclopropylsulfonyl)-1H - pyrazol - 4 - yl)pyrimidin - 4 - yl)amino)-4-(4 - (hydroxymethyl)-4 - methylpiperidin - 1 - yl)pyridin - 3 - yl)ethynyl)pyridin - 2 - yl)(morpholino)methanone; (266) 2 - (3 - ((6 - ((2 - (1 - (cyclopropylsulfonyl)-1H - pyrazol - 4 - yl)pyrimidin - 4 - yl)amino)-4-(4 - (hydroxymethyl)-4 - methylpiperidin - 1 - yl)pyridin - 3 - yl)ethynyl)cyclobutyl)propan - 2 - ol; (267) (1 - (2 - ((2 - (1 - (2,2 - difluoroethyl)-1H - pyrazol - 4 - yl)pyrimidin - 4 - yl)amino)-5 - ((1 - (trifluoromethyl)-1H - pyrazol - 4 - yl)ethynyl)pyridin - 4 - yl)-4 - methylpiperidin - 4 - yl)methanol; (268) (4-Methyl-1-(2-((2-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)methanol; (269) (1-(2-((2-(6-fluoropyridin-3-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (270) (4-Methyl-1-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-2-((2-((2-(methylsulfonyl)phenyl)amino)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-yl)methanol; (271) (1-(5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)-2-((2-((2-(methylsulfonyl)phenyl)amino)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (272) 4-(4-((4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)amino)pyrimidin-2-yl)-N,N,3-trimethyl-1H-pyrazole-1-sulfonamide; (273) 4-(4-((4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)amino)pyrimidin-2-yl)-N,N-dimethyl-1H-pyrazole-1-sulfonamide; (274) 4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)but-3-yn-1-ol; (275) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(4,4,4-trifluorobut-1-yn-1-yl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (276) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(4-fluorobut-1-yn-1-yl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (277) (1-(5-(But-3-en-1-yn-1-yl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (278) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-((dimethylamino)methyl)pyridin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (279) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((6-((4-methylpiperazin-1-yl)methyl)pyridin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (280) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(pyridin-3-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol; (281) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-methoxy-4-methylpiperidin-1-yl)-5-(pyridin-3-ylethynyl)pyridin-2-yl)pyrimidin-4-amine; (282) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-(pyridin-3-ylethynyl)-4-(1-oxa-8-azaspiro[4.5]dec-8-yl)pyridin-2-yl)pyrimidin-4-amine; (283) 2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-(pyridin-3-ylethynyl)-4-(1-oxa-7-azaspiro[3.5]nonan-7-yl)pyridin-2-yl)pyrimidin-4-amine; (284) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)-2-methylpent-4-yn-2-ol; (285) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(4-morpholinobut-1-yn-1-yl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (286) 3-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)prop-2-yn-1-yl)oxetan-3-ol; (287) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)pent-4-yn-2-ol; (288) N-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)prop-2-yn-1-yl)-2,2,2-trifluoroacetamide; (289) 4-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)prop-2-yn-1-yl)thiomorpholine 1,1-dioxide; (290) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-(trifluoromethyl)-1H-pyrazol-5-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (291) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-(trifluoromethyl)thiazol-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (292) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-(trifluoromethyl)thiazol-5-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (293) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-fluoropiperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine formate; (294) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine formate; (295) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((dimethylamino)methyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin- ​ (297) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)pyridin-2-yl)pyrimidin-4-amine formate; (298) N-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)piperidin-1-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (299) N-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-methylpiperidin-1-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (300) N-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-fluoropiperidin-1-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (301) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (302) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-methylpiperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (303) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine; (304) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-(hydroxymethyl)cyclohexan-1-ol; (305) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (306) (1R,3S)-3-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclopentan-1-ol; (307) (1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol; (308) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (309) 5-((1-(Cyclopropylmethyl)-1H-pyrazol-4-yl)ethynyl)-N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((Dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine; (310) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -((1s,4s)-4-((Dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine; (311) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-N 4 -((1s,4s)-4-((Dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine; (312) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((Dimethylamino)methyl)cyclohexyl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (313) 5-((1-Cyclopropyl-1H-pyrazol-4-yl)ethynyl)-N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((Dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine; (314) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((Dimethylamino)methyl)cyclohexyl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (315) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-((dimethylamino)methyl)piperidin-4-ol; (316) 1-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-((dimethylamino)methyl)piperidin-4-ol; (317) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-((dimethylamino)methyl)piperidin-4-ol; (318) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-methyl-1H-pyrazol-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-2-yl)pyrimidin-4-amine; (319) N-(5-((1-cyclopropyl-1H-pyrazol-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (320) N-(5-((1-(Cyclopropylmethyl)-1H-pyrazol-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (321) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-2-yl)pyrimidin-4-amine; (322) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-2-yl)pyrimidin-4-amine; (323) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol; (324) ((1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (325) 2-((1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)propan-2-ol; (326) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol; (327) ((1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (328) 1-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol; (329) 2-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)propan-2-ol; (330) 1-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)cyclopropan-1-ol; (331) ((1R,5S,6r)-3-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3-azabicyclo[3.1.0]hexan-6-yl)methanol; (332) ((1R,3s,5S)-8-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-8-azabicyclo[3.2.1]octan-3-yl)methanol; (333) ((1S,5S)-3-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)methanol; (334) 1-(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-4-yl)ethan-1-one; (335) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (336) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (337) 2-((1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)propan-2-ol; (338) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol; (339) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (340) ((1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (341) (1S,3S)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (342) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-fluoropiperidin-4-yl)methanol; (343) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol; (344) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)-1-methylcyclohexan-1-ol; (345) N 2 -(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N 4 -((1s,4s)-4-((2-Fluoroethyl)amino)cyclohexyl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridine-2,4-diamine; (346) 2-((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)propan-2-ol; (347) 7-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol; (348) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (349) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (350) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-methyloxetan-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (351) 1-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)cyclobutan-1-ol; (352) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(oxetan-3-ylethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (353) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(oxetan-3-ylethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (354) 3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)oxetan-3-ol; (355) 3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)tetrahydrofuran-3-ol; (356) 3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridin-3-yl)ethynyl)tetrahydrofuran-3-ol; (357) 3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)tetrahydro-2H-pyran-3-ol; (358) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (359) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (360) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (361) (1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol; (362) (5s,8s)-8-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)-1-azaspiro[4.5]decan-2-one; (363) (1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)amino)methyl)-1-methylcyclohexan-1-ol; (364) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidin-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol; (365) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidin-2-yl)ethynyl)pyridin-4-yl)-4-methoxypiperidin-4-ol; (366) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((5-(morpholinomethyl)pyrimidin-2-yl)ethynyl)-4-(1-oxa-8-azaspiro[4.5]decan-8-yl)pyridin-2-yl)pyrimidin-4-amine; (367) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((5-(Morpholinomethyl)pyrimidin-2-yl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonan-7-yl)pyridin-2-yl)pyrimidin-4-amine; (368) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-Methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol; (369) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((4-((4-Methylpiperazin-1-yl)methyl)phenyl)ethynyl)pyridin-4-yl)-4-methoxypiperidin-4-ol; (370) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((4-((4-Methylpiperazin-1-yl)methyl)phenyl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonan-7-yl)pyridin-2-yl)pyrimidin-4-amine; (371) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-Methylpyrrolidin-3-yl)ethynyl)pyridin-4-yl)-4-methoxypiperidin-4-ol; (372) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-Methylpyrrolidin-3-yl)ethynyl)-4-(1-oxa-8-azaspiro[4.5]decane-8-yl)pyridin-2-yl)pyrimidin-4-amine; (373) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(5-((1-Methylpyrrolidin-3-yl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonan-7-yl)pyridin-2-yl)pyrimidin-4-amine; (374) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (375) (1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol; (376) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (377) (1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)amino)methyl)-1-methylcyclohexan-1-ol; (378) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (379) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (380) (1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)methyl)-1-methylcyclohexan-1-ol; (381) ((1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexyl)methanol; (382) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoro-4-(((methylamino)methyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (383) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-fluoro-4-((((2-fluoroethyl)amino)methyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (384) (S)-2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-((dimethylamino)methyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (385) (S)-2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-((dimethylamino)methyl)piperidin-1-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (386) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (387) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (388) ((1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexyl)methanol; (389) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (390) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (391) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (392) ((1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidin-4-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexyl)methanol; (393) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (394) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (395) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (396) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(3-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (397) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (398) (1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol; (399) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (400) ((1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-�yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexyl)methanol; (401) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (402) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (403) (1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol; (404) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol; (405) ((1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexyl)methanol; (406) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-methylpiperidin-1-yl)-5-((1-methylcyclopropyl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (407) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-((1-methylcyclopropyl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (408) 1-(3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one; (409) 1-(3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-((((1r,4r)-4-hydroxycyclohexyl)methyl)amino)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one; (410) 1-(3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-hydroxymethylpiperidin-1-yl)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one; (411) 1-(3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-((((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)amino)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one; (412) 1-(3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-((dimethylamino)methyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one; (413) 1-(3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one; (414) 1-(3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one; (415) 1-(3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)pyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one; (416) ((1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (417) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol; (418) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-methylpiperidin-1-yl)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (419) 2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-2-yl)pyrimidin-4-amine; (420) (1S,4S)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (421) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (422) ((1s,4s)-4-((5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexyl)methanol; (423) (1r,4r)-4-(((5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)methyl)cyclohexan-1-ol; (424) 1-(5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)-4-methylpiperidin-4-ol; (425) ((1r,4r)-4-(((5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)methyl)cyclohexyl)methanol; (426) N-(5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-amine; (427) (1s,4s)-4-((5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)pyridin-4-yl)amino)cyclohexan-1-ol; (428) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridin-3-yl)ethynyl)tetrahydrothiophene 1,1-dioxide; (429) 3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-hydroxy-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)tetrahydrothiophene 1,1-dioxide; (430) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (431) (1r,4r)-4-(((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)methyl)cyclohexan-1-ol; (432) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol; (433) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (434) ((1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexyl)methanol; (435) 1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-ol; (436) (1s,4s)-4-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)amino)cyclohexan-1-ol; (437) 3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)tetrahydrothiophene 1,1-dioxide; (438) (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol; (439) (S)-1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol; (440) (R)-1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol; (441) (4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone; (442) (4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-hydroxy-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone; (443) (4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-((((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)amino)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone; (444) (R)-(4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone; (445) (S)-(4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone; (446) (4-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidin-1-yl)pyridin-3-yl)ethynyl)phenyl)(4-hydroxypiperidin-1-yl)methanone; (447) (S)-1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3-methylpiperidin-3-ol; (448) (S)-1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-�yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-3-methylpiperidin-3-ol; and (449) (1-(2-((2-(4-(Cyclopropylsulfonyl)piperazin-1-yl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)-4-methylpiperidin-4-yl)methanol The compound according to claim 1 selected from the group consisting of or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition for treating a protein kinase-mediated disease, comprising as an active ingredient the compound according to any one of claims 1 to 14 or a pharmaceutically acceptable salt thereof.

16. The pharmaceutical composition according to claim 15, wherein the protein kinase-mediated disease is cancer or an immune disease.

17. The pharmaceutical composition according to claim 16, wherein the cancer is bladder cancer, colorectal cancer, brain cancer, breast cancer, ovarian cancer, endometrial cancer, uterine cancer, heart cancer, kidney cancer, lung cancer, liver cancer, gastric cancer, lymphoma, pancreatic cancer, head and neck cancer, thyroid cancer, prostate cancer, skin cancer, or a hematological tumor.

18. The pharmaceutical composition according to claim 16, wherein the cancer is lung cancer.

19. The pharmaceutical composition according to claim 16, wherein the cancer is non-small cell lung cancer.

20. A pharmaceutical composition for selectively inhibiting at least one variant of EGFR as compared to wild-type EGFR, comprising as an active ingredient the compound according to any one of claims 1 to 14 or a pharmaceutically acceptable salt thereof.

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