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] This invention relates to a novel aminopyridine compound that exhibits inhibitory activity against specific mutants of EGFR, and to a pharmaceutically acceptable composition thereof. [Background technology]

[0002] Another subtype of lung cancer is non-small cell lung cancer (NSCLC) that is positive for epidermal growth factor receptor (EGFR) mutations. 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 control intercellular communication during development, including proliferation, migration, differentiation, and apoptosis (Wee et al., 2017; Huang et al., 2015; Yewale et al., 2013).

[0003] Approximately 10% to 50% of NSCLC patients have EGFR-activating mutations such as in-frame deletions of exon 19 (Del19) or missense mutations of 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 TMIt responds well to first and second-generation EGFR tyrosine kinase inhibitors (TKIs) such as ) and can be used as initial treatment for patients with progressive NSCLC who have common EGFR mutations (Kashima et al., 2020; Mok et al., 2009; Zhou et al., 2011; Sequist et al., 2013). However, ultimate acquired resistance to treatment with gefitinib or erlotinib is mainly due to mutations in the gatekeeper residue T790M, which is detected in about half of clinically resistant patients, resulting in double mutants, L858R / T790M and Del19 / T790M.

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

[0005] Osimertinib is a potent inhibitor that blocks EGFR mutations and T790M resistance mutations, but it causes ineffective binding and subsequent C797S resistance in NSCLC patients (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 in 10% to 30% of these patients after the use of third-generation EGFR TKIs (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 needed to overcome osimertinib-resistant EGFR triple mutations (Kashima et al., 2020).

[0006] In first-line treatment with third-generation TKIs, C797S develops in the absence of T790M (Chen et al., 2020). Osimertinib was approved in 2018 as a first-line therapy for locally advanced or metastatic EGFR-mutated NSCLC, regardless of the T790M mutation status (Leonetti et al., 2019). When osimertinib was administered as first-line treatment, the frequency of C797S mutations was 7%, making it the second most common mechanism of drug resistance 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 the 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. This is because inhibition of WT EGFR causes side effects such as rash and diarrhea, and these WT EGFR-derived toxicities lead to dose-limiting effects (Kashima et al., 2020; Fakih et al., 2010; Takeda et al., 2015).

[0008] Next-generation EGFR compounds need to inhibit Del19 / T790M / C797S, L858R / T790M / C797S, Del19 / C797S, and L858R / C797S, and be highly selective for WT EGFR, in order to avoid side effects. Recently, the mutation-selective inhibitors BI-4020 and BLU-945 have been reported as potential therapeutic strategies for overcoming 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 C797S triple and double variants. Depending on the secondary or primary use of third-generation EGFR TKIs, there is a need to develop novel selective (next-generation) inhibitors for NSCLC patients with progressive or metastatic disease who have Del19 / T790M / C797S, L858R / T790M / C797S, Del19 / C797S, and L858R / C797S mutations.

[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, randomised, phase 3 study. Lancet Oncol. 2011; 12:735-42. Zhou Z, Zhao Y, Shen S, Gu L,Niu X, Xu Y, et al. Durable clinical response of lung adenocarcinoma harboring EGFR 19Del / T790M / in trans-C797S to combination therapy of first- and third-generation EGFR tyrosine kinase inhibitors. J. Thorac. Oncol. 2019; 14:e157-e9.

Summary of the Invention

Means for Solving the Problems

[0012] The present invention relates to a novel aminopyridine compound of the following chemical formula (I) or a pharmaceutically acceptable salt thereof:

Chemical Formula

[0013] The present invention also relates to a method for treating a protein kinase-mediated disease, particularly a variant EGFR-mediated disease, in a subject requiring treatment, comprising administering to the subject a therapeutically effective amount of a compound of chemical formula (I) or a pharmaceutically acceptable salt thereof.

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

[0015] Detailed description of the invention The present invention will be described in more detail below.

[0016] Unless otherwise defined, all technical terms used herein have the same meaning as generally understood by those skilled in the art to which the invention pertains. Furthermore, while the invention has been described in relation to specific methods and samples, their analogues or equivalents should also be within the scope of the invention. In addition, numerical values ​​mentioned herein are to be considered "approximately" unless expressly stated otherwise. All publications and other references mentioned herein are incorporated herein by reference in their entirety.

[0017] The definitions of residues used herein are explained in detail. Unless otherwise specified, each residue has the following definition and is used in the sense generally 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 C 1-6 alkyl, preferably C 1-4 alkyl, more preferably C 1-3 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, the definition of an alkyl group as given 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 alkyl groups are defined as shown 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 are substituted with a hydroxyl group.

[0026] As used herein, "amino" refers to -NH2.

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

[0028] As used herein, the term “aryl” means a compound derived by removing one hydrogen atom from a single carbon atom of an aromatic ring system, for example, 6 to 20 carbon atoms (C 6-20 The term refers to a monovalent aromatic hydrocarbon having a C18 ring. Aryls may also 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, etc. Unless otherwise defined, aryl means C18 ring. 6-12 Aryl, preferably C 6-10 It refers to the arrow.

[0029] As used herein, “heterocyclyl” refers to a saturated or partially unsaturated monocyclic, dicyclic, or polycyclic system of an aromatic molecule containing a certain number of ring atoms, comprising one or more heteroatoms selected from N, O, and S, where the heterocyclyl ring is connected to the base molecule via a ring atom of C or N. Dicyclic systems may be connected via 1,1-fusion (spiro), 1,2-fusion (condensation), or 1,>2-fusion (bridgehead).

[0030] As used herein, “heteroaryl” refers to a monovalent or divalent substituent derived from a monoheterocyclic or polyheterocyclic aromatic hydrocarbon having 1 to 10 carbon ring members and containing one or more heteroatoms selected from N, O, and S, preferably 1 to 3 heteroatoms. Examples of heteroaryls include, but are not limited to, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridadinyl, 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, phlopyridinyl, and their analogues. Unless otherwise defined, a heteroaryl is a 4- to 12-membered heteroaryl, preferably a 4- to 10-membered heteroaryl, more preferably a 4- to 7-membered heteroaryl.

[0031] As used herein, "heterocycloalkyl" refers to a monocyclic, bicyclic, tricyclic, or more cyclic alkyl group having 3 to 10 carbon ring members and containing one or more heteroatoms selected from N, O, and S, for example, 1 to 4 heteroatoms. Furthermore, the heterocycloalkyl group according to the present invention may be a condensed or crosslinked heterocycloalkyl group. 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, piperadinyl, tetrahydropyranyl, dihydropyranyl, tetrahydropyridinyl, dihydropyranyl, dihydrothiopyranyl, tetrahydropyrimidinyl, tetrahydropyridadinyl, dihydropyranyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydropyrazolopyridinyl, morpholinyl, indolinyl, thiomorpholinyl, azepanyl, diazepanyl, azaadamantanyl, and diazamantanyl. The bonding of heterocycloalkyl substituents may occur via carbon atoms or heteroatoms. Heterocycloalkyl groups 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 group, preferably a 4- to 10-membered heterocycloalkyl group, more preferably a 4- to 7-membered heterocycloalkyl group.

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

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

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

[0035] In one embodiment, compounds of the following chemical formula (I), pharmaceutically acceptable salts thereof, diastereomers, enantiomers, racemates, tautomers, prodrugs, hydrates, or solvates are provided herein. [ka] During the ceremony, R1 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,-NHC(O)C 1-6 Alkyl, -NHC(O)C 1-6 Haloalkyl, -NHC(O)C 3-6 Cycloalkyl, -NHC(O)-4~7 member heterocyclyl, -C(O)-4~7 member heterocyclyl, and C 1-6 C11 is a 4- to 7-membered heterocycline that is 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 Alkenil; -C(O)NHC 1-6 alkyl; -C(O)N(C 1-6 Alkyl)2; -C(O)-4~7 member heterocyclyl; -NHCs are optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogens. 1-6 alkyl; -N(C) is optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogens. 1-6 Alkyl)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 aryls; 4-8 member heterocyclyls; and 5-10 member heteroaryls, R 1A teeth, H; OH; NH2; 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-4~7 member 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 A C12C 1-6 alkyl; OH, halogens, and -N(C) 1-6 C is optionally substituted with one or more substituents selected from the group consisting of alkyl)2. 3-6 Cycloalkyl; -C(O)C is optionally substituted with one or more substituents selected from the group consisting of OH and halogens. 1-6 alkyl; -C(O)N(C 1-6 Alkyl)2; -C(O)-4~7 member heterocyclines optionally substituted with one or more substituents selected from the group consisting of OH and halogens; -NHCs are arbitrarily substituted with 4- to 7-membered heterocyclines. 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 is optionally substituted with alkyl)2 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Haloalkyl, -C(O)C 1-6 4-11 member heterocyclines that are optionally or independently substituted with one or more substituents selected from the group consisting of alkyl groups and 4-7 member heterocyclines. Independently selected from the group consisting of, m is an integer between 0 and 2. R2 is optionally substituted with one or more OH groups -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 which is optionally substituted with alkyl)2 1-6 Alkyl; and -X(CH2) n -B-(R 2A ) o Selected from the group consisting of, X is a bond, -NH-, or -O-, n is an integer between 0 and 1. o is an integer between 0 and 3. B is C 3-7Cycloalkyl; C 6-10 Selected from the group consisting of aryls; 4-12 member heterocyclils; and 5-6 member heteroaryls, R 2A teeth, H; OH; halogen; OH, halogen, -NHC 1-6 Alkyl, -NHC 1-6 Haloalkyl, -N(C) 1-6 Alkyl) 2, 4-7 member heterocyclyl, and C 1-3 C is optionally or independently substituted with one or more substituents selected from the group consisting of alkoxys. 1-6 alkyl; C is optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogens. 3-6 Cycloalkyl; C is 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 -NHCs are optionally or independently substituted with one or more substituents selected from the group consisting of alkyl)2 and 4- to 7-membered heterocyclines. 1-6 alkyl; -NHCs are optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogens. 3-6 Cycloalkyl; -N(C) is optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogens. 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 heterocycline optionally or independently substituted with one or more substituents selected from the group consisting of alkyl groups; =O; and C(O)C 1-6 Alkyl Independently selected from the group consisting of, R3 is YQ-(R 3A ) p And, Y is -NH- or a bond, p is an integer between 0 and 2. Q is a 4-7 member heterocycline; C 6-10 Selected from the group consisting of aryls and 5-6 member heteroaryls, R 3A H; halogen; halogen and C 3-6 C is optionally substituted with one or more substituents selected from the group consisting of cycloalkyl groups. 1-6 Alkyl; C 3-6 Cycloalkyl; 4-7 member heterocycline; optionally substituted with 1-3 halogens -S(O)2C 1-6 Alkyl; optionally substituted with one or more halogens -S(O)2C 3-6 Cycloalkyl; and -S(O)2N(C 1-6 Independently selected from the group consisting of alkyls, R4 is H, halogen, and C 1-6 Selected from the group consisting of alkyl groups.

[0036] In a particular embodiment, R1 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)-4~6 member heterocyclil, -C(O)-4~6 member heterocyclil having 1~3 heteroatoms selected from the group consisting of N, O, and S, and C 1-4 C is optionally or independently substituted with 1 to 3 substituents selected from the group consisting of 4 to 6 member heterocyclyl molecules 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 -C(O)-4-6 member heterocyclyl having 1-3 heteroatoms selected from the group consisting of N, O, and S; -NHC which is optionally or independently substituted with 1-3 substituents selected from the group consisting of OH, F, and Cl. 1-4 Alkyl; -N(C) is 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 It is selected from the group consisting of the following.

[0037] Furthermore, in certain embodiments, R1 is -H;-Si(C 1-6 Alkyl)3;OH, halogen, C 1-3 Alkoxy, -NHC(O)C 1-6 C11 is a 4- to 7-membered heterocycline that is optionally or independently substituted with one or more substituents selected from the group consisting of haloalkyls, -NHC(O)-4 to 7-membered heterocyclines, -C(O)-4 to 7-membered heterocyclines, and 4 to 7-membered heterocyclines that are optionally or independently substituted with oxo substituents. 1-6 Alkyl; C 2-5 Alkenyl; and -A-(R 1A ) m It is selected from the group consisting of the following.

[0038] In the above embodiment of R1, the 4- to 7-membered heterocyclyl may be selected from the group consisting of morpholinil, pyrrolidinil, 1,1-dioxo-1,4-thiadinil, and oxetanil.

[0039] In a particular embodiment, A is C 3-6 The group is selected from cycloalkyl; phenyl; 4-7 member heterocycloalkyl; 5-6 member heteroaryl; and 9-10 member heteroaryl.

[0040] Furthermore, in a particular embodiment, A is C 3-6 Selected from the group consisting of cycloalkyl; phenyl; pyrazolyl; pyridinyl; 4,5,6,7-tetrahydropyrazolo[1,5-a]pyradinyl; 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 a particular embodiment, R 1A 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 -C(O)N-4 to 7-membered heterocyclyl having 1 to 3 heteroatoms selected from the group consisting of alkyl)2, 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 1-4A 4-7 member heterocyclyl having 1-3 heteroatoms selected from the group consisting of N, O, and S, which are optionally substituted with 1-3 substituents selected from the group consisting of alkyls, and a C 1-4 alkyl;OH, F, Cl, and -N(C) 1-4 C is 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)2; -C(O)-4-7 member heterocyclil having 1-3 heteroatoms selected from the group consisting of N, O, and S, optionally substituted with 1-3 OH groups; -NHC 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 is optionally substituted with alkyl)2 1-4 Alkyl, C 3-6 Cycloalkyl, C 1-4 Haloalkyl, -C(O)C 1-4 The group consists of 4- to 11-membered heterocyclines that are optionally or independently substituted with 1-3 substituents selected from the group consisting of alkyl and 4- to 7-membered heterocyclines having 1-3 heteroatoms selected from the group consisting of N, O, and S.

[0042] Furthermore, in a specific embodiment, 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)2, -C(O)N-4~7 member 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 A C12C 1-6 alkyl;OH, halogen, and -N(C) 1-6 C is 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 is optionally substituted with alkyl)2 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Haloalkyl, -C(O)C 1-6 The group consists of 4- to 7-membered heterocyclines that are optionally or independently substituted with one or more substituents selected from the group consisting of alkyls and 4- to 7-membered heterocyclines.

[0043] In yet another, more specific embodiment, R 1A teeth, H; OH; NH2; halogen; OH, halogen, C 3-6 Cycloalkyl, -N(C 1-6 Alkyl)2,-C(O)N(C 1-6 Alkyl)2, and halogens and C 1-6 A C12C 1-6 alkyl; C is optionally substituted with one or more halogens. 3-6 Cycloalkyl; -C(O)C that is optionally substituted with one or more halogens 1-6 alkyl; -C(O)N(C 1-6 Alkyl)2; -C(O)-4~7 member heterocyclyls arbitrarily substituted with one or more OH groups; -NHCs are arbitrarily substituted with 4- to 7-membered heterocyclines. 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 heterocyclines that are optionally or independently substituted with one or more substituents selected from the group consisting of alkyl groups. It is selected from the group consisting of the following.

[0044] R 1A In the above embodiments, the 4-7 member heterocyclil or 4-11 member heterocyclil may be selected from the group consisting of tetrahydropyranil, piperidinil, azetidinil, morpholinil, piperazinil, dioxanil, tetrahydrofuranil, and oxetanil.

[0045] In certain embodiments, R2 is optionally or independently substituted with 1 to 3 OH groups -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 which is optionally substituted with alkyl)2 1-4 Alkyl; and X(CH2) n -B-(R 2A ) o Selected from the group consisting of, where X is conjugate, -NH-, or -O-; n is an integer between 0 and 1; and o is an integer between 0 and 3.

[0046] In yet another, more specific embodiment, R2 is optionally substituted with one or more OH groups -N(C 1-6-XC which is optionally substituted with alkyl)2;OH 1-6 Alkyl; and -X(CH2) n -B-(R 2A ) o It is selected from the group consisting of the following.

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

[0048] In yet another, more specific embodiment, B is C 3-6 Selected from the group consisting of cycloalkyl;phenyl;piperazinyl, piperidinyl, 4-oxopiperidinyl, azaspiro[3.5]nonanyl, pyrrolidinyl, azetidinyl, azepanyl, 2,8-diazaspiro[4.5]decanoyl, 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]decanoyl.

[0049] In a particular embodiment, R 2A 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 is optionally or independently substituted with 1 to 3 substituents selected from the group consisting of alkoxys. 1-6 Alkyl; C is optionally substituted with 1 to 3 OH groups. 3-6 Cycloalkyl; C is 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 -NHCs are optionally or independently substituted with one or more substituents selected from the group consisting of alkyl)2 and 4-7 membered heterocyclines having 1-3 heteroatoms selected from the group consisting of N, O, and S. 1-4 Alkyl;NHC -NHC is optionally or independently substituted with 1 to 3 substituents selected from the group consisting of OH, F, and Cl. 3-6 Cycloalkyl; -N(C) is 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 A 4-7 member heterocyclyl having 1-3 heteroatoms selected from the group consisting of N, O, and S, which are optionally or independently substituted with 1-3 substituents selected from the group consisting of alkyls;-C(O)C 1-6 It is independently selected from the group consisting of alkyl and =O.

[0050] Furthermore, in a specific embodiment, 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 is optionally or independently substituted with one or more substituents selected from the group consisting of alkoxys. 1-6 Alkyl; C 3-6 Cycloalkyl;OH, halogen, C 3-6 Cycloalkyl, C 1-3 Alkoxy, -NHC 1-6Alkyl, -N(C 1-6 -NHCs are optionally or independently substituted with one or more substituents selected from the group consisting of alkyl)2 and 4- to 7-membered heterocyclines. 1-6 -NHCs are optionally or independently substituted with one or more substituents selected from the group consisting of alkyl, OH, and halogens. 3-6 -N(C) is optionally or independently substituted with one or more substituents selected from the group consisting of cycloalkyl, OH, and halogens. 1-6 It is independently selected from the group consisting of alkyl)2.

[0051] In yet another, more specific embodiment, R 2A teeth, H; OH; halogen; OH, halogen, -NHC 1-6 Alkyl, -NHC 1-6 Haloalkyl and -N(C 1-6 C is optionally or independently substituted with one or more substituents selected from the group consisting of alkyl)2. 1-6 alkyl; C is substituted arbitrarily or independently by one or more OH groups. 3-6 Cycloalkyl; C is 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 -NHC which is optionally or independently substituted with one or more substituents selected from the group consisting of alkyl)2. 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 heterocycline optionally or independently substituted with one or more substituents selected from the group consisting of alkyl groups; =O; and C(O)C 1-6 Alkyl It is independently selected from the group consisting of [the specified elements].

[0052] R 2A In the above embodiments, the 4- to 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 a particular embodiment, R 3A H; halogen; F, Cl, and C 3-6 C is optionally substituted with 1 to 3 substituents selected from the group consisting of cycloalkyl groups. 1-4 Alkyl; C 3-6 Cycloalkyl; 4-7 membered heterocyclyl having 1-3 heteroatoms selected from the group consisting of N, O, and S; -S(O)2C 1-4 Alkyl; -S(O)2C optionally substituted with 1-3 F and Cl atoms. 3-6 Cycloalkyl; and -S(O)2N(C 1-4 Selected from the group consisting of alkyl groups.

[0055] Furthermore, in certain embodiments, R3 is a halogen; C is 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)2N(C 1-6 Selected from the group consisting of alkyl groups.

[0056] In certain embodiments, R4 is H.

[0057] The following is a list of representative compounds with chemical formula (I).

[0058] (1) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-methylpiperazine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0059] (2) N 4 -Cyclohexyl-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-2,4-diamine;

[0060] (3) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(ethylsulfonyl)piperazine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0061] (4) (R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)butan-1-ol;

[0062] (5) (S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)-2-methylbutan-2-ol;

[0063] (6) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol;

[0064] (7) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-one;

[0065] (8) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoropiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0066] (9) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol;

[0067] (10) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0068] (11) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)propan-2-ol;

[0069] (12) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0070] (13) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0071] (14) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-2-methylpropan-1-ol;

[0072] (15) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-methoxypiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0073] (16) 2-(4-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperazine-1-yl)ethane-1-ol;

[0074] (17) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0075] (18) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine;

[0076] (19) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-Isopropyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine;

[0077] (20) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine;

[0078] (21) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(pyridine-3-ylethinyl)pyridine-2,4-diamine;

[0079] (22) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(4-methoxybuto-1-in-1-yl)pyridine-2,4-diamine;

[0080] (23) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine;

[0081] (24) N 4 -(sec-butyl)-N 2-(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-2,4-diamine;

[0082] (25) N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-isopropyl-1H-pyrazole-4-yl)ethinyl)pyridine-2,4-diamine;

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

[0084] (27) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol;

[0085] (28) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol;

[0086] (29) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol;

[0087] (30) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol;

[0088] (31) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-3-ol;

[0089] (32) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-3-ol;

[0090] (33) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-yl)methanol;

[0091] (34) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-yl)methanol;

[0092] (35) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-3-yl)propan-2-ol;

[0093] (36) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-3-yl)propan-2-ol;

[0094] (37) 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)(methyl)amino)ethane-1-ol;

[0095] (38) 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)(methyl)amino)ethane-1-ol;

[0096] (39) 3-((2-((2-(1-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-yl)amino)-5-(2-(1-methylpyrazole-4-yl)ethinyl)-4-pyridyl)amino)-2,2-dimethyl-propane-1-ol;

[0097] (40) 3-((2-((2-(1-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-yl)amino)-5-(2-(1-(2-fluoroethyl)pyrazole-4-yl)ethinyl)-4-pyridyl)amino)-2,2-dimethyl-propane-1-ol;

[0098] (41) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0099] (42) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0100] (43) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0101] (44) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0102] (45) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0103] (46) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0104] (47) (1-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0105] (48) (1-(5-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0106] (49) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

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

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

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

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

[0111] (54) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-isopropoxy-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0112] (55) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-isopropoxypyridine-2-yl)pyrimidine-4-amine;

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

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

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

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

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

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

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

[0120] (63) N-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanesulfonamide;

[0121] (64) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(isopropylamino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0122] (65) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-(trifluoromethyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0123] (66) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoro-4-(trifluoromethyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0124] (67) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-(trifluoromethoxy)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0125] (68) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-3,3-difluoropiperidine-4-ol;

[0126] (69) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-3,3-dimethylpiperidine-4-ol;

[0127] (70) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-fluoropiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0128] (71) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(3-(trifluoromethyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0129] (72) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-(fluoromethyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0130] (73) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

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

[0132] (75) (1R,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0133] (76) (1R,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0134] (77) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azepan-4-ol;

[0135] (78) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azepan-4-yl)methanol;

[0136] (79) 8-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-2,8-diazaspiro[4.5]decane-1-one;

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

[0138] (81) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol;

[0139] (82) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-ol;

[0140] (83) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol;

[0141] (84) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0142] (85) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0143] (86) 1-(5-((5-cyclopropyl-1-methyl-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)piperidine-4-ol;

[0144] (87) 2-(1-(5-((5-cyclopropyl-1-methyl-1H-pyrazole-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0145] (88) (1s,4s)-4-((5-((5-cyclopropyl-1-methyl-1H-pyrazole-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)cyclohexane-1-ol;

[0146] (89) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-ol;

[0147] (90) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol;

[0148] (91) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0149] (92) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0150] (93) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-one;

[0151] (94) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0152] (95) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0153] (96) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

[0154] (97) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoropiperidine-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0155] (98) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-methoxypiperidine-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0156] (99) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol;

[0157] (100) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-yl)methanol;

[0158] (101) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0159] (102) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0160] (103) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0161] (104) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0162] (105) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol;

[0163] (106) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0164] (107) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0165] (108) 1-(5-((1-(1-acetylpiperidine-4-yl)-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)piperidine-4-one;

[0166] (109) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0167] (110) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0168] (111) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-fluoro-4-(hydroxymethyl)piperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0169] (112) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-fluoropiperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0170] (113) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-methoxypiperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0171] (114) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(3-hydroxypiperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0172] (115) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(3-(hydroxymethyl)piperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0173] (116) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0174] (117) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

[0175] (118) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol;

[0176] (119) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0177] (120) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0178] (121) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

[0179] (122) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol;

[0180] (123) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0181] (124) N-(4-(4-((cyclopropylmethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine;

[0182] (125) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(isopentylamino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0183] (126) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2,2-difluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0184] (127) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-((3,3,3-trifluoropropyl)amino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0185] (128) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(3,3-difluoroazetidine-1-yl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0186] (129) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0187] (130) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-(methylamino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0188] (131) 2-((1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)amino)ethane-1-ol;

[0189] (132) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-methoxyethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0190] (133) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-N 2 ,N 2 -Dimethylethane-1,2-diamine;

[0191] (134) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-N 2 ,N 2 ,2-trimethylpropane-1,2-diamine;

[0192] (135) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-((2,2,2-trifluoroethyl)amino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0193] (136) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidine-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0194] (137) 2-((1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)amino)ethane-1-ol;

[0195] (138) N 1 -(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-N 2 ,N 2 -Dimethylethane-1,2-diamine;

[0196] (139) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-((2-(dimethylamino)ethyl)amino)piperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0197] (140) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-3-yl)ethynyl)-4-(4-(methylamino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0198] (141) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0199] (142) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-3-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-N 2 ,N 2 -Dimethylethane-1,2-diamine;

[0200] (143) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-N 2 ,N 2 -Dimethylethane-1,2-diamine;

[0201] (144) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)-4-(4-((2-fluoroethyl)amino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0202] (145) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)-4-(4-((2-fluoroethyl)amino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0203] (146) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-methyl-4-((methylamino)methyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0204] (147) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(1-methylpiperidine-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0205] (148) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(1-methylazetidine-3-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0206] (149) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0207] (150) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0208] (151) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(2,2-difluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

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

[0210] (153) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-(2-(methylamino)ethyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0211] (154) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(2,8-diazaspiro[4.5]decane-2-yl)pyridine-2-yl)pyrimidine-4-amine;

[0212] (155) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethinyl)-4-(2,7-diazaspiro[3.5]nonanane-2-yl)pyridine-2-yl)pyrimidine-4-amine;

[0213] (156) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(2,8-diazaspiro[4.5]decane-8-yl)pyridine-2-yl)pyrimidine-4-amine;

[0214] (157) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0215] (158) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol;

[0216] (159) (1R,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0217] (160) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0218] (161) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

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

[0220] (163) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0221] (164) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0222] (165) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(3-morpholinoprop-1-in-1-yl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0223] (166) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(3-morpholinoprop-1-in-1-yl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol;

[0224] (167) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1,2,4-triazole-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0225] (168) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-ethylthiazole-2-yl)ethinyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0226] (169) (1S,3R)-3-((5-((3-aminophenyl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)cyclohexane-1-ol;

[0227] (170) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-methylpyrazine-2-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0228] (171) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(3-(pyrrolidine-1-yl)prop-1-in-1-yl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0229] (172) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((2-morpholinoethyl)amino)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0230] (173) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-((2-morpholinoethyl)amino)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0231] (174) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridine-3-yl)ethynyl)cyclohexane-1-ol;

[0232] (175) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)cyclohexane-1-ol;

[0233] (176) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-hydroxycyclopentyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0234] (177) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)cyclopentan-1-ol;

[0235] (178) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0236] (179) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0237] (180) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylpyrrolidine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0238] (181) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylpyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0239] (182) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylpiperidine-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0240] (183) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-methyltetrahydro-2H-pyran-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0241] (184) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyridine-2-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0242] (185) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyridine-2-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0243] (186) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-(morpholinomethyl)pyridine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0244] (187) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-(morpholinomethyl)pyridine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0245] (188) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(morpholinomethyl)thiazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0246] (189) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(morpholinomethyl)thiazole-4-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0247] (190) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)thiophen-2-yl)ethinyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0248] (191) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)thiophen-2-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0249] (192) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(morpholinomethyl)thiazole-5-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0250] (193) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidine-2-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0251] (194) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidine-2-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0252] (195) 4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)tetrahydro-2H-pyran-4-ol;

[0253] (196) 4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridine-3-yl)ethinyl)tetrahydro-2H-pyran-4-ol;

[0254] (197) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0255] (198) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0256] (199) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((2-methylthiazole-4-yl)ethinyl)pyridine-2,4-diamine;

[0257] (200) N 2- (2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((2-(fluoromethyl)thiazole-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine;

[0258] (201) 4-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)prop-2-in-1-yl)thiomorpholine 1,1-dioxide;

[0259] (202) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(3-morpholinoprop-1-in-1-yl)pyridine-2,4-diamine;

[0260] (203) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(3-(pyrrolidine-1-yl)prop-1-in-1-yl)pyridine-2,4-diamine;

[0261] (204) 4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)-2-methylbuto-3-in-2-ol;

[0262] (205) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((2-cyclopropylthiazole-4-yl)ethinyl)-N 4 -Isopropylpyridine-2,4-diamine;

[0263] (206) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)pento-4-in-1-yl)morpholine-4-carboxamide;

[0265] (208) 6-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)-1-morpholinohex-5-in-1-one;

[0266] (209) N-(6-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)hex-5-in-1-yl)morpholine-4-carboxamide;

[0267] (210) 7-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)-1-morpholinohepto-6-in-1-one;

[0268] (211) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methylthiazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol;

[0269] (212) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(fluoromethyl)thiazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol;

[0270] (213) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-imidazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol;

[0271] (214) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-1,2,4-triazole-3-yl)ethinyl)pyridine-4-yl)piperidine-4-ol;

[0272] (215) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-morpholinopyridine-3-yl)ethinyl)pyridine-4-yl)piperidine-4-ol;

[0273] (216) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-imidazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0274] (217) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(thiophene-3-ylethinyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0275] (218) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0276] (219) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-morpholinoethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0277] (220) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol;

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

[0279] (222) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methylthiazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclopentan-1-ol;

[0280] (223) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-imidazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclopentan-1-ol;

[0281] (224) 3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-imidazole-4-yl)ethinyl)pyridine-4-yl)amino)-2,2-dimethylpropane-1-ol;

[0282] (225) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(thiophene-3-ylethinyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0283] (226) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)-5-(thiophene-3-ylethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0284] (227) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-morpholinopyridine-3-yl)ethinyl)pyridine-4-yl)piperidine-3-ol;

[0285] (228) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(thiophene-3-ylethinyl)pyridine-4-yl)piperidine-3-ol;

[0286] (229) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(thiophene-3-ylethinyl)pyridine-4-yl)-3,3-dimethylpiperidine-4-ol;

[0287] (230) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(3-methyl-3-morpholinbut-1-in-1-yl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0288] (231) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0289] (232) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-morpholinoethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0290] (233) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(1-methyl-1H-pyrazole-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0291] (234) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-(1-methyl-1H-pyrazole-4-yl)pyridine-2-yl)pyrimidine-4-amine;

[0292] (235) N-(4-(1-cyclopropyl-1H-pyrazole-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine;

[0293] (236) N-(4-(1-cyclopropyl-1H-pyrazole-4-yl)-5-((1-isopropyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine;

[0294] (237) N-(4-(1-cyclopropyl-1H-pyrazole-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine;

[0295] (238) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((2-methylthiazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0296] (239) 4-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)pyridine-3-yl)prop-2-in-1-yl)thiomorpholine 1,1-dioxide;

[0297] (240) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-(3-(pyrrolidine-1-yl)prop-1-in-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0298] (241) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-3-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0299] (242) (1-(5-((1-((1,4-dioxan-2-yl)methyl)-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0300] (243) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydrofuran-3-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0301] (244) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0302] (245) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(oxetan-3-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0303] (246) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((trimethylsilyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0304] (247) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-ethynylpyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0305] (248) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-((3,3-difluoroazetidine-1-yl)methyl)-1-(2,2-difluoroethyl)-1H-pyrrole-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0306] (249) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrrolo[3,2-c]pyridine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0307] (250) (1-(5-(cyclopropylethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0308] (251) (1-(5-(cyclopentylethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0309] (252) (1-(5-(cyclohexylethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0310] (253) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0311] (254) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((dimethylaminomethyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0312] (255) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-((dimethylamino)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0313] (256) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(phenylethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0314] (257) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-fluorophenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0315] (258) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-4-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0316] (259) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-2-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0317] (260) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-3-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0318] (261) (3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(morpholino)methanone;

[0319] (262) 4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)-N,N-dimethylbenzamide;

[0320] (263) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(morpholino)methanone;

[0321] (264) 6-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)-N,N-dimethylpicolinamide;

[0322] (265) (6-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)pyridine-2-yl)(morpholino)methanone;

[0323] (266) 2-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)cyclobutyl)propan-2-ol;

[0324] (267) (1-(2-((2-(1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0325] (268) (4-methyl-1-(2-((2-(1-(methylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol;

[0326] (269) (1-(2-((2-(6-fluoropyridine-3-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0327] (270) (4-methyl-1-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-2-((2-((2-(methylsulfonyl)phenyl)amino)pyrimidine-4-yl)amino)pyridine-4-yl)piperidine-4-yl)methanol;

[0328] (271) (1-(5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)-2-((2-((2-(methylsulfonyl)phenyl)amino)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0329] (272) 4-(4-((4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)amino)pyrimidine-2-yl)-N,N,3-trimethyl-1H-pyrazole-1-sulfonamide;

[0330] (273) 4-(4-((4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)amino)pyrimidine-2-yl)-N,N-dimethyl-1H-pyrazole-1-sulfonamide;

[0331] (274) 4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)buto-3-in-1-ol;

[0332] (275) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(4,4,4-trifluorobuto-1-in-1-yl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0333] (276) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(4-fluorobuto-1-in-1-yl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0334] (277) (1-(5-(buto-3-en-1-in-1-yl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0335] (278) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-((dimethylamino)methyl)pyridine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0336] (279) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-((4-methylpiperazine-1-yl)methyl)pyridine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0337] (280) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-3-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol;

[0338] (281) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-methoxy-4-methylpiperidine-1-yl)-5-(pyridine-3-ylethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0339] (282) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-(pyridine-3-ylethynyl)-4-(1-oxa-8-azaspiro[4.5]decane-8-yl)pyridine-2-yl)pyrimidine-4-amine;

[0340] (283) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-(pyridine-3-ylethynyl)-4-(1-oxa-7-azaspiro[3.5]nonane-7-yl)pyridine-2-yl)pyrimidine-4-amine;

[0341] (284) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)-2-methylpent-4-in-2-ol;

[0342] (285) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(4-morpholinbut-1-in-1-yl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0343] (286) 3-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)prop-2-in-1-yl)oxetan-3-ol;

[0344] (287) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)pento-4-in-2-ol;

[0345] (288) N-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)prop-2-in-1-yl)-2,2,2-trifluoroacetamide;

[0346] (289) 4-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)prop-2-in-1-yl)thiomorpholine 1,1-dioxide;

[0347] (290) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-(trifluoromethyl)-1H-pyrazole-5-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0348] (291) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(trifluoromethyl)thiazole-2-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0349] (292) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(trifluoromethyl)thiazole-5-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0350] (293) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-fluoropiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine formate;

[0351] (294) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine formate;

[0352] (295) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((dimethylamino)methyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0353] (296) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0354] (297) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethinyl)-4-(2-methyl-2,8-diazaspiro[4.5]decane-8-yl)pyridine-2-yl)pyrimidine-4-amine formate;

[0355] (298) N-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)piperidine-1-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine;

[0356] (299) N-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine;

[0357] (300) N-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-fluoropiperidine-1-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine;

[0358] (301) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0359] (302) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0360] (303) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0361] (304) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-(hydroxymethyl)cyclohexane-1-ol;

[0362] (305) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0363] (306) (1R,3S)-3-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)methyl)cyclopentan-1-ol;

[0364] (307) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol;

[0365] (308) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

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

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

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

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

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

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

[0372] (315) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-((dimethylamino)methyl)piperidine-4-ol;

[0373] (316) 1-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-((dimethylamino)methyl)piperidine-4-ol;

[0374] (317) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-((dimethylamino)methyl)piperidine-4-ol;

[0375] (318) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecane-3-yl)pyridine-2-yl)pyrimidine-4-amine;

[0376] (319) N-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethinyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecane-3-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine;

[0377] (320) N-(5-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)ethinyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecane-3-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine;

[0378] (321) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecane-3-yl)pyridine-2-yl)pyrimidine-4-amine;

[0379] (322) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecane-3-yl)pyridine-2-yl)pyrimidine-4-amine;

[0380] (323) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol;

[0381] (324) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0382] (325) 2-((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclohexyl)propan-2-ol;

[0383] (326) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol;

[0384] (327) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0385] (328) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0386] (329) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)propan-2-ol;

[0387] (330) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)cyclopropane-1-ol;

[0388] (331) ((1R,5S,6r)-3-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-3-azabicyclo[3.1.0]hexane-6-yl)methanol;

[0389] (332) ((1R,3s,5S)-8-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-8-azabicyclo[3.2.1]octan-3-yl)methanol;

[0390] (333) ((1S,5S)-3-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-3-azabicyclo[3.1.0]hexane-1-yl)methanol;

[0391] (334) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-one;

[0392] (335) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0393] (336) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0394] (337) 2-((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclohexyl)propan-2-ol;

[0395] (338) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

[0396] (339) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0397] (340) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0398] (341) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0399] (342) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

[0400] (343) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-ol;

[0401] (344) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol;

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

[0403] (346) 2-((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)propan-2-ol;

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

[0405] (348) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0406] (349) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0407] (350) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-methyloxetane-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0408] (351) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)cyclobutan-1-ol;

[0409] (352) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(oxetane-3-ylethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0410] (353) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(oxetane-3-ylethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0411] (354) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)oxetan-3-ol;

[0412] (355) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)tetrahydrofuran-3-ol;

[0413] (356) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridine-3-yl)ethynyl)tetrahydrofuran-3-ol;

[0414] (357) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)tetrahydro-2H-pyran-3-ol;

[0415] (358) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0416] (359) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0417] (360) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0418] (361) (1r,4r)-4-(((2-((2-((1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol;

[0419] (362) (5s,8s)-8-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)-1-azaspiro[4.5]decane-2-one;

[0420] (363) (1r,4r)-4-(((2-((2-((1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)methyl)-1-methylcyclohexane-1-ol;

[0421] (364) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidine-2-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-ol;

[0422] (365) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidine-2-yl)ethinyl)pyridine-4-yl)-4-methoxypiperidine-4-ol;

[0423] (366) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((5-(morpholinomethyl)pyrimidine-2-yl)ethynyl)-4-(1-oxa-8-azaspiro[4.5]decane-8-yl)pyridine-2-yl)pyrimidine-4-amine;

[0424] (367) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((5-(morpholinomethyl)pyrimidine-2-yl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonanane-7-yl)pyridine-2-yl)pyrimidine-4-amine;

[0425] (368) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol;

[0426] (369) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methoxypiperidine-4-ol;

[0427] (370) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonanane-7-yl)pyridine-2-yl)pyrimidine-4-amine;

[0428] (371) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylpyrrolidine-3-yl)ethynyl)pyridine-4-yl)-4-methoxypiperidine-4-ol;

[0429] (372) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methylpyrrolidine-3-yl)ethynyl)-4-(1-oxa-8-azaspiro[4.5]decane-8-yl)pyridine-2-yl)pyrimidine-4-amine;

[0430] (373) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methylpyrrolidine-3-yl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonanane-7-yl)pyridine-2-yl)pyrimidine-4-amine;

[0431] (374) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0432] (375) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol;

[0433] (376) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0434] (377) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)amino)methyl)-1-methylcyclohexane-1-ol;

[0435] (378) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0436] (379) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0437] (380) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)methyl)-1-methylcyclohexane-1-ol;

[0438] (381) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexyl)methanol;

[0439] (382) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoro-4-((methylamino)methyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0440] (383) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoro-4-(((2-fluoroethyl)amino)methyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0441] (384) (S)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-((dimethylamino)methyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0442] (385) (S)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-((dimethylamino)methyl)piperidine-1-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0443] (386) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0444] (387) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0445] (388) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexyl)methanol;

[0446] (389) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0447] (390) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0448] (391) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0449] (392) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexyl)methanol;

[0450] (393) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0451] (394) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0452] (395) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0453] (396) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0454] (397) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0455] (398) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol;

[0456] (399) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0457] (400) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexyl)methanol;

[0458] (401) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0459] (402) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0460] (403) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol;

[0461] (404) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol;

[0462] (405) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexyl)methanol;

[0463] (406) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)-5-((1-methylcyclopropyl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0464] (407) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-methylcyclopropyl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0465] (408) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one;

[0466] (409) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-((((1r,4r)-4-hydroxycyclohexyl)methyl)amino)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one;

[0467] (410) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-hydroxy-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one;

[0468] (411) 1-(3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-((((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)amino)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one;

[0469] (412) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one;

[0470] (413) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one;

[0471] (414) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one;

[0472] (415) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one;

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

[0474] (417) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol;

[0475] (418) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0476] (419) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0477] (420) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0478] (421) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0479] (422) ((1s,4s)-4-((5-((7-Oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)methyl)cyclohexane-1-ol;

[0481] (424) 1-(5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-ol;

[0482] (425) ((1r,4r)-4-(((5-((7-Oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)methyl)cyclohexyl)methanol;

[0483] (426) N-(5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine;

[0484] (427) (1s,4s)-4-((5-((7-Oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)cyclohexane-1-ol;

[0485] (428) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridine-3-yl)ethinyl)tetrahydrothiophene 1,1-dioxide;

[0486] (429) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-hydroxy-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)tetrahydrothiophene 1,1-dioxide;

[0487] (430) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0488] (431) (1r,4r)-4-(((2-((2-((1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol;

[0489] (432) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol;

[0490] (433) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0491] (434) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0492] (435) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol;

[0493] (436) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0494] (437) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)tetrahydrothiophene 1,1-dioxide;

[0495] (438) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0496] (439) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol;

[0497] (440) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol;

[0498] (441) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone;

[0499] (442) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-hydroxy-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone;

[0500] (443) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-((((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)amino)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone;

[0501] (444) (R)-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(3-hydroxypiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone;

[0502] (445) (S)-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(3-hydroxypiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone;

[0503] (446) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone;

[0504] (447) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-3-methylpiperidine-3-ol;

[0505] (448) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-3-methylpiperidine-3-ol; and

[0506] (449) (1-(2-((2-(4-(cyclopropylsulfonyl)piperazin-1-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol.

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

[0508] (1) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-methylpiperazine-1-yl)pyridine-2-yl)pyrimidine-4-amine;

[0509] (4) (R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)butan-1-ol;

[0510] (5) (S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)-2-methylbutan-2-ol;

[0511] (6) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol;

[0512] (7) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-one;

[0513] (8) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoropiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0514] (9) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol;

[0515] (10) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0516] (11) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)propan-2-ol;

[0517] (12) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0518] (13) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0519] (14) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-2-methylpropan-1-ol;

[0520] (15) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-methoxypiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0521] (17) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0522] (18) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine;

[0523] (19) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-Isopropyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine;

[0524] (20) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine;

[0525] (21) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(pyridine-3-ylethinyl)pyridine-2,4-diamine;

[0526] (23) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine;

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

[0528] (27) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol;

[0529] (28) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol;

[0530] (29) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol;

[0531] (30) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol;

[0532] (31) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-3-ol;

[0533] (32) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-3-ol;

[0534] (33) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-yl)methanol;

[0535] (34) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-yl)methanol;

[0536] (35) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-3-yl)propan-2-ol;

[0537] (39) 3-((2-((2-(1-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-yl)amino)-5-(2-(1-methylpyrazole-4-yl)ethinyl)-4-pyridyl)amino)-2,2-dimethyl-propane-1-ol;

[0538] (40) 3-((2-((2-(1-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-yl)amino)-5-(2-(1-(2-fluoroethyl)pyrazole-4-yl)ethinyl)-4-pyridyl)amino)-2,2-dimethyl-propane-1-ol;

[0539] (41) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0540] (42) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0541] (43) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0542] (44) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0543] (45) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0544] (47) (1-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0545] (48) (1-(5-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0546] (49) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

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

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

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

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

[0551] (68) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-3,3-difluoropiperidine-4-ol;

[0552] (73) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

[0553] (75) (1R,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0554] (81) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol;

[0555] (82) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-ol;

[0556] (83) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol;

[0557] (84) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0558] (85) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0559] (86) 1-(5-((5-cyclopropyl-1-methyl-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)piperidine-4-ol;

[0560] (87) 2-(1-(5-((5-cyclopropyl-1-methyl-1H-pyrazole-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0561] (88) (1s,4s)-4-((5-((5-cyclopropyl-1-methyl-1H-pyrazole-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)cyclohexane-1-ol;

[0562] (90) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol;

[0563] (91) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0564] (94) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0565] (95) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0566] (96) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

[0567] (99) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol;

[0568] (100) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-yl)methanol;

[0569] (101) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0570] (106) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0571] (107) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0572] (110) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0573] (112) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-fluoropiperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0574] (113) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-methoxypiperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0575] (114) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(3-hydroxypiperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one;

[0576] (116) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0577] (117) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

[0578] (118) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol;

[0579] (119) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0580] (120) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0581] (121) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

[0582] (122) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol;

[0583] (123) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0584] (126) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2,2-difluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0585] (129) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0586] (136) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidine-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0587] (147) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(1-methylpiperidine-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0588] (148) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(1-methylazetidine-3-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0589] (149) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0590] (150) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

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

[0592] (157) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0593] (164) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0594] (169) (1S,3R)-3-((5-((3-aminophenyl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)cyclohexane-1-ol;

[0595] (177) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)cyclopentan-1-ol;

[0596] (178) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0597] (179) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0598] (180) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylpyrrolidine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0599] (182) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylpiperidine-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0600] (185) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyridine-2-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0601] (186) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-(morpholinomethyl)pyridine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0602] (187) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-(morpholinomethyl)pyridine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0603] (189) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(morpholinomethyl)thiazole-4-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0604] (191) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)thiophen-2-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0605] (192) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(morpholinomethyl)thiazole-5-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0606] (193) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidine-2-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0607] (197) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0608] (207) N-(5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)pento-4-in-1-yl)morpholine-4-carboxamide;

[0609] (210) 7-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)-1-morpholinohepto-6-in-1-one;

[0610] (211) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methylthiazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol;

[0611] (216) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-imidazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0612] (217) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(thiophene-3-ylethinyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0613] (218) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0614] (219) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-morpholinoethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0615] (220) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol;

[0616] (231) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0617] (232) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-morpholinoethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0618] (238) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((2-methylthiazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0619] (241) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-3-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0620] (242) (1-(5-((1-((1,4-dioxan-2-yl)methyl)-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0621] (243) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydrofuran-3-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0622] (244) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0623] (245) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(oxetan-3-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0624] (248) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-((3,3-difluoroazetidine-1-yl)methyl)-1-(2,2-difluoroethyl)-1H-pyrrole-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0625] (253) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0626] (254) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((dimethylaminomethyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0627] (255) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-((dimethylamino)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0628] (258) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-4-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0629] (260) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-3-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0630] (261) (3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(morpholino)methanone;

[0631] (262) 4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)-N,N-dimethylbenzamide;

[0632] (263) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(morpholino)methanone;

[0633] (264) 6-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)-N,N-dimethylpicolinamide;

[0634] (266) 2-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)cyclobutyl)propan-2-ol;

[0635] (274) 4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)buto-3-in-1-ol;

[0636] (276) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(4-fluorobuto-1-in-1-yl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0637] (277) (1-(5-(buto-3-en-1-in-1-yl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0638] (278) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-((dimethylamino)methyl)pyridine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0639] (279) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-((4-methylpiperazine-1-yl)methyl)pyridine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0640] (280) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-3-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol;

[0641] (283) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-(pyridine-3-ylethynyl)-4-(1-oxa-7-azaspiro[3.5]nonane-7-yl)pyridine-2-yl)pyrimidine-4-amine;

[0642] (284) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)-2-methylpent-4-in-2-ol;

[0643] (287) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)pento-4-in-2-ol;

[0644] (288) N-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)prop-2-in-1-yl)-2,2,2-trifluoroacetamide;

[0645] (294) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine formate;

[0646] (305) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0647] (306) (1R,3S)-3-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)methyl)cyclopentan-1-ol;

[0648] (308) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

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

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

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

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

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

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

[0655] (324) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0656] (327) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0657] (339) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0658] (340) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0659] (342) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

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

[0661] (348) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0662] (352) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(oxetane-3-ylethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0663] (353) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(oxetane-3-ylethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0664] (358) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0665] (360) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0666] (368) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol;

[0667] (374) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0668] (376) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0669] (378) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0670] (379) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0671] (396) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0672] (397) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0673] (399) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0674] (401) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0675] (402) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0676] (404) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol;

[0677] (407) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-methylcyclopropyl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0678] (408) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one;

[0679] (422) ((1s,4s)-4-((5-((7-Oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)cyclohexane-1-ol;

[0681] (430) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0682] (433) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0683] (442) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-hydroxy-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone;

[0684] (446) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone; and

[0685] (447) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-3-methylpiperidine-3-ol.

[0686] The following are some more preferred representative compounds of chemical formula (I).

[0687] (6) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol;

[0688] (10) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0689] (12) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0690] (13) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0691] (18) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine;

[0692] (19) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-Isopropyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine;

[0693] (20) N2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine;

[0694] (27) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol;

[0695] (30) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol;

[0696] (35) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-3-yl)propan-2-ol;

[0697] (39) 3-((2-((2-(1-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-yl)amino)-5-(2-(1-methylpyrazole-4-yl)ethinyl)-4-pyridyl)amino)-2,2-dimethyl-propane-1-ol;

[0698] (41) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0699] (43) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0700] (47) (1-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0701] (49) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0702] (73) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol;

[0703] (82) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-ol;

[0704] (85) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0705] (101) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0706] (126) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2,2-difluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0707] (129) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine;

[0708] (157) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol;

[0709] (260) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-3-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0710] (305) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0711] (324) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0712] (327) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol;

[0713] (360) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; and

[0714] (379) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol.

[0715] The following are some more preferred representative compounds of chemical formula (I).

[0716] (6) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol;

[0717] (10) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol;

[0718] (12) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0719] (13) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol;

[0720] (35) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-3-yl)propan-2-ol;

[0721] (47) (1-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0722] (49) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0723] (101) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol;

[0724] (126) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2,2-difluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; and

[0725] (129) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine.

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

[0727] Acid addition salts can be prepared by reacting a purified compound, preferably in free base form, with a suitable organic or inorganic acid and isolating the resulting salt. 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 produced by reacting a purified compound in acid form with a suitable organic or inorganic base and isolating the resulting salt. Such salts include alkali metals (e.g., sodium, lithium, and potassium), alkaline earth metals (e.g., magnesium and calcium), ammonium, and N + (C 1-4 Examples include, but are not limited to, salts of alkyl(4) compounds.

[0729] Other pharmaceutically acceptable salts include adipine, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptone, glycerophosphate, glycolate, gluconic acid, glycolic acid, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, and 2-hydroxy Examples include ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, palminate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivaphosphate, 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 the methods shown in Examples 1 to 449 below.

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

[0732] As used herein, the term “cancer” refers to the abnormal proliferation of cells that tend to grow uncontrollably and, in some cases, metastasize. Types of cancer 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 cancers (thyroid cancer), prostate cancer, skin cancer (melanoma), or hematological malignancies (such as leukemia). In another embodiment, cancer is non-small cell lung cancer (NSCLC).

[0733] In one embodiment, the method disclosed herein relates to the treatment of cancer resulting from at least one mutation in EGFR.

[0734] In one embodiment, the cancer treatment method is particularly useful for patients resistant to the compounds of the present invention, or to kinase inhibitors other than 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 variant of EGFR in a biological sample or patient compared to wild-type EGFR, comprising contacting the biological sample with a therapeutically effective amount of the compound of the present invention or a pharmaceutically acceptable salt thereof, or administering a therapeutically effective amount of the compound of the present invention or a pharmaceutically acceptable salt thereof to a patient.

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

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

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

[0739] [Table 1]

[0740] The present invention also relates to therapeutic methods and uses, comprising administering the compound of the present invention, or a pharmaceutically acceptable salt thereof, diastereomer, enantiomer, racemate, tautomer, prodrug, hydrate, or solvate, alone or in combination with other therapeutic or palliative agents.

[0741] Further embodiments of the present invention relate to the compounds of the present invention for use as pharmaceuticals, and in particular to the compounds of the present invention for use in the treatment of diseases in which inhibition of mutated EGFR protein activity (e.g., those listed in Table 1) can induce benefits, such as cancer. Further embodiments of the present invention relate to the use of the compounds of the present invention, or pharmaceutically acceptable salts thereof, diastereomers, enantiomers, racemates, tautomers, prodrugs, hydrates or solvates, for the production of drugs 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 "therapeutic dose" refers to the amount of a compound administered that reduces, to some extent, one or more symptoms of the disorder being treated. In the context of cancer treatment, a therapeutic dose refers to the amount that has the effect of reducing tumor size, inhibiting (i.e., delaying or stopping) tumor metastasis, inhibiting (i.e., delaying or stopping) tumor growth or invasion, and / or reducing, to some extent, one or more signs or symptoms associated with cancer.

[0743] The therapeutically effective dose can be easily determined by a physician skilled in the art using standard techniques and observing results obtained under similar circumstances. When determining the therapeutically effective dose, the attending physician considers many factors, including but not limited to: the species of mammal; its size, age, and general health; the specific disease involved; the degree or severity of the disease's involvement; the individual patient's response; the specific compound administered; the method of administration; the bioavailability characteristics of the administered formulation; the selected dose regimen; the use of concomitant medications; and other relevant circumstances.

[0744] As used herein, the term “to treat” means, unless otherwise specified, reversing, reducing, inhibiting the progression of, or preventing one or more symptoms of the disorder or condition to which such term applies. The term “treatment” also refers to the act of treating, as “to treat” is defined immediately before it. The term “to treat” also includes adjuvant treatment in mammals.

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

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

[0747] The administration of the compounds of the present invention can be achieved by any method that enables delivery of the compounds to the site of action. These methods include oral routes, intraduodenal routes, parenteral injections (including intravenous, subcutaneous, intramuscular, intravascular, or infusion), topical, and rectal administration.

[0748] In other embodiments, pharmaceutical compositions comprising a compound of chemical formula (I), a pharmaceutically acceptable salt thereof, a diastereomer, an enantiomer, a racemate, a tautomer, a prodrug, a hydrate, or a solvate thereof, and a pharmaceutically acceptable additive as an active ingredient are provided herein. In one embodiment, the pharmaceutical composition is for the treatment of a protein kinase-mediated disease. In another embodiment, the pharmaceutical composition is for the selective inhibition of at least one variant of EGFR compared to wild-type EGFR.

[0749] The compounds of the present invention can be administered orally. Oral administration may involve swallowing so that the compound enters the gastrointestinal tract, or it may be administered orally or sublingually so that the compound enters the bloodstream directly from the mouth. Formulations suitable for oral administration include solid formulations such as tablets, capsules containing particles, liquids or powders, lozenges (including liquid fillers), chewables, multiparticles and nanoparticles, gels, solid solutions, liposomes, films (including mucosal adhesives), ovules, sprays and liquid formulations.

[0750] Liquid formulations include suspensions, solutions, syrups, and elixirs. Such formulations can be used as fillers in soft or hard capsules and typically contain a carrier, such as water, ethanol, polyethylene glycol, propylene glycol, methylcellulose, or a suitable oil, and one or more emulsifiers and / or suspending agents. Liquid formulations can also be produced by reconstituting solids.

[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, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. When formulating the product, commonly used fillers, stabilizers, binders, disintegrants, surfactants, and other diluents and additives can be used. Examples of solid formulations for oral administration include tablets, pills, powders, granules, and capsules. These solid formulations can be produced by mixing the compound of the present invention with at least one additive, such as starch, crystalline cellulose, sucrose, lactose, low-substituted hydroxypropylcellulose, hypromellose, etc. In addition to simple additives, lubricants such as magnesium stearate and talc can also be used. Oral administration liquid preparations include suspensions, oral solutions, emulsions, and syrups. In addition to commonly used simple diluents such as water and liquid paraffin, they may contain various additives such as humectants, sweeteners, fragrances, and preservatives. Parenteral administration 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 injection esters such as ethyl oleate. Suppository bases include whitepsol, macrogol, tween 61, cocoa butter, laurine butter, and glycerol gelatin. To formulate parenteral administration formulations, the compound of chemical formula I or a pharmaceutically acceptable salt thereof is sterilized and mixed in water and / or contains adjuvants such as preservatives, stabilizers, hydrated powders or emulsifiers, osmotic salts and / or buffers, and other therapeutically useful substances to produce a solution or suspension, which is then manufactured into ampoule or vial unit dosage forms.

[0752] Overview of general reaction schemes and synthesis routes The present invention includes, within its scope, a method for producing a compound of chemical formula (I) or a pharmaceutically acceptable salt thereof according to the following reaction formula 1: [ka] In the reaction equation, R1, R2, R3, and R4 are the same as described above. X is a halogen. M is hydrogen, B(OH)2, or BPin.

[0753] Specifically, the compound of chemical formula (I) or a pharmaceutically acceptable salt thereof can be produced by a manufacturing method comprising the following steps: reacting the compound of chemical formula (II) with R2-M to obtain the compound of chemical formula (IV); reacting the compound of chemical formula (IV) with the compound of chemical formula (III) to obtain the compound of chemical formula (VI); and reacting the compound of chemical formula (VI) with the compound of chemical formula (VII) to obtain the compound of chemical formula (I).

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

[0755] The Sonogashira reaction couples the compound of chemical formula (IV) with the compound of chemical formula (III) to obtain the compound of chemical formula (VI). The reaction of the compounds of chemical formulas (IV) and (III) may be carried out in the presence of a base such as TEA or diethylamine, and a palladium complex and copper(I) halide such as PdCl2(PPh3)2, Pd(PPh3)4, or copper(I) iodide as a catalyst. Alternatively, the reaction may be carried out in an organic solvent such as TEA or DMF at room temperature or under heating, for example, at a temperature of 40-100°C.

[0756] Alternatively, the compound of chemical formula (VI) may be produced by reacting the compound of chemical formula (II) with the compound of chemical formula (III) to obtain the compound of chemical formula (V), and then reacting the compound of chemical formula (V) with R2-M.

[0757] The Sonogashira reaction couples the compound of chemical formula (II) with the compound of chemical formula (III) to obtain the compound of chemical formula (V). The reaction of the compounds of chemical formulas (II) and (III) may be carried out in the presence of a base such as TEA or diethylamine, and a palladium complex and copper(I) halide such as PdCl2(PPh3)2, Pd(PPh3)4, or copper(I) iodide as a catalyst. Alternatively, the reaction may be carried out in an organic solvent such as TEA or DMF at room temperature or under heating, for example, at a temperature of 40-100°C.

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

[0759] The compound of chemical formula (VI) is coupled with the compound of chemical formula (VII) by the Buchwald-Hartwig reaction to obtain the compound of chemical formula (I). The reaction of the compounds of chemical formulas (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. Furthermore, the reaction may be carried out in anhydrous organic solvent, such as 1,4-dioxane or toluene, under heating, for example, at a temperature of 80-120°C.

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

[0761] Specifically, a compound of chemical formula (I) or a pharmaceutically acceptable salt thereof can be produced by a manufacturing method comprising the following steps: removing a protecting group from a compound of chemical formula (Ia) to obtain a compound of chemical formula (Ib); and reacting the compound of chemical formula (Ib) with R1-X to obtain a compound of chemical formula (I).

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

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

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

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

[0766] Examples The present invention is further illustrated by the following examples illustrating the preparation of the compound of chemical formula (I) according to the present invention. The examples are for illustrative purposes only and are not intended to limit the present invention in any way, nor should they be construed as limiting the present invention. Those skilled in the art will understand that modifications and alterations can be made without altering 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 analyzed in ppm. The stated molecular weights were measured using an Agilent 1260 Infinity series liquid chromatography / mass selective detector (MSD) with an electrostatic spray interface (using a single quadrupole, the m / z value in ESI+ (ESI-MS (cation)) is shown as the [M + H]+ peak). Column chromatography was performed on silica gel (Merck, 70-230 mesH) (WCStill, J.Org.Chem., 43, 2923, 1978). The starting materials in each example are known compounds, synthesized according to the literature or obtained from commercially available products such as Sigma-Aldrich. The abbreviations used in the following examples are as follows:

[0768] [Table 2]

[0769] Manufacturing Example 1: N-(sec-butyl)-2-chloro-5-iodopyridine-4-amine A suspension of 2-chloro-5-iodopyridine-4-amine (1.00 g, 3.930 mmol), 2-iodobutane (0.54 mL, 4.716 mmol), and Cs2CO3 (2.56 g, 7.680 mmol) in 1,4-dioxane (10 mL) was stirred overnight at 80°C. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-10%) to obtain N-(sec-butyl)-2-chloro-5-iodopyridine-4-amine (134 mg) as a pale yellow oil. MS (ESI) m / z = 311.0 (M+H) +

[0770] Manufacturing example 2: 1-(2-chloro-5-iodopyridine-4-yl)piperidine-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 overnight at 100°C. After cooling the reaction mixture, it 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 obtain 1-(2-chloro-5-iodopyridine-4-yl)piperidine-4-ol (468 mg) as a yellow solid. MS (ESI) m / z = 339.0 (M+H) +

[0771] Production Example 3: (1-(2-chloro-5-iodopyridine-4-yl)piperidine-4-yl)methanol The title compound (458 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing Example 4: (R)-1-(2-chloro-5-iodopyridine-4-yl)pyrrolidine-3-ol The title compound (245.1 mg) was prepared in solid form in the same manner as in Preparation Example 2, except that (R)-pyrrolidine-3-ol HCl (270 mg, 2.191 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 325.0 (M+H) +

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

[0774] Manufacturing example 6: 2-(1-(2-chloro-5-iodopyridine-4-yl)azetidine-3-yl)propan-2-ol The title compound (261 mg) was prepared in solid form in the same manner as in Preparation Example 2, except that 2-(azetidine-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] Manufacturing example 7: 2-((2-chloro-5-iodopyridine-4-yl)(methyl)amino)ethane-1-ol The title compound (569 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing example 8: 3-((2-chloro-5-iodopyridine-4-yl)amino)-2,2-dimethylpropane-1-ol The title compound (319 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing Example 9: (1s,4s)-4-((2-chloro-5-iodopyridine-4-yl)amino)cyclohexane-1-ol The title compound (836 mg) was prepared in solid form in the same manner as in Preparation Example 2, except that (1s,4s)-4-aminocyclohexane-1-ol HCl (1.06 g, 6.992 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 353.0 (M+H) +

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

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

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

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

[0782] Manufacturing Example 14: 2-Chloro-5-iodo-4-isopropoxypyridine 2,4-Dichloro-5-iodopyridine (500 mg, 1.826 mmol) and NaH (109 mg, 2.738 mmol) were suspended in THF (10 mL) and 2-propanol (131 mg, 2.191 mmol). The reaction mixture was stirred at room temperature for 2 hours, then 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 obtain 2-chloro-5-iodo-4-isopropoxypyridine (270 mg) as an off-white solid. MS (ESI) m / z = 298.0 (M+H) +

[0783] Manufacturing 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 Example 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] Manufacturing Example 16: 1-((1r,4r)-4-(((2-chloro-5-iodopyridine-4-yl)oxy)methyl)cyclohexyl)-N,N-dimethylmethaneamine Step 1: tert-butyl (((1r,4r)-4-(((2-chloro-5-iodopyridine-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 Example 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-iodopyridine-4-yl)oxy)methyl)cyclohexyl)-N,N-dimethylmethaneamine A 20% TFA DCM (10 mL) solution of tert-butyl (((1r,4r)-4-(((2-chloro-5-iodopyridine-4-yl)oxy)methyl)cyclohexyl)methyl)carbamate (1.00 g, 2.080 mmol) prepared in Step 1 was stirred overnight at room temperature. The reaction mixture was quenched with saturated NaHCO3 solution, extracted with DCM, dried over MgSO4, and then 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 overnight at 60°C, quenched with saturated NaHCO3 solution, extracted with DCM, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-10%) to obtain 1-((1r,4r)-4-(((2-chloro-5-iodopyridine-4-yl)oxy)methyl)cyclohexyl)-N,N-dimethylmethaneamine (549 mg) as an off-white solid. MS (ESI) m / z = 409.0 (M+H) +

[0785] Manufacturing Example 17: tert-butyl (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)carbamate Step 1: tert-butyl (1-(2-chloro-5-iodopyridine-4-yl)piperidine-4-yl)carbamate The title compound (1.65 g) was prepared as a solid in the same manner as in Preparation Example 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-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)carbamate The mixture of tert-butyl (1-(2-chloro-5-iodopyridine-4-yl)piperidine-4-yl)carbamate (1.5 g, 3.427 mmol), 4-ethynyl-1-methylpyrazole (436 mg, 4.112 mmol), PdCl2(PPh3)2 (120 mg, 0.171 mmol), and CuI (130.6 mg, 0.685 mmol) prepared in Step 1 was filled with nitrogen gas for 10 minutes. After adding DMF (30 mL) and TEA (0.96 mL, 6.854 mmol), the reaction mixture was stirred at 50°C for 1 hour. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-10%) to obtain tert-butyl (1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)carbamate A suspension of 2-(1-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-amine (428 mg, 1.615 mmol), tert-butyl (1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)carbamate prepared in step 2 (590 mg, 1.468 mmol), Cs2CO3 (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 hours. The reaction mixture was cooled, filtered through Celite, and then concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-100%) to obtain tert-butyl (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)carbamate (372 mg) as a yellow solid. MS (ESI) m / z = 645.3 (M+H) +

[0786] Manufacturing Example 18: 2-Chloro-4-fluoro-5-((1-methyl-1H-pyrazole-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), PdCl2(PPh3)2 (477 mg, 0.680 mmol), and CuI (518 mg, 2.719 mmol) was packed with nitrogen gas for 10 minutes. After adding DMF (40 mL) and TEA (3.79 mL, 27.192 mmol), the reaction mixture was stirred at 50°C for 1 hour. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-40%) to obtain 2-chloro-4-fluoro-5-((1-methyl-1H-pyrazole-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] Manufacturing Example 19: 2-Chloro-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)-4-fluoropyridine The title compound (669.6 mg) was prepared as a solid in the same manner as in Preparation Example 18, except that 1-(2,2-difluorocyclopropyl)-4-ethinylpyrazole (517 mg, 3.077 mmol) was used instead of 4-ethinyl-1-methylpyrazole. MS (ESI) m / z = 298.0 (M+H) +

[0788] Manufacturing Example 20: 2-Chloro-5-((5-cyclopropyl-1-methyl-1H-pyrazole-4-yl)ethynyl)-4-fluoropyridine The title compound (545 mg) was prepared as a solid in the same manner as in Preparation Example 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] Manufacturing Example 21: 2-Chloro-4-fluoro-5-(2-(1-methyl-3-(trifluoromethyl)pyrazole-4-yl)ethynyl)pyridine The title compound (651 mg) was prepared as a solid, in the same manner as in Preparation Example 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] Manufacturing Example 22: 2-Chloro-4-fluoro-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethinyl)pyridine The title compound (838 mg) was prepared as a solid in the same manner as in Preparation Example 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] Manufacturing Example 23: 2-Chloro-4-fluoro-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine The title compound (460 mg) was prepared as a solid in the same manner as in Preparation Example 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] Manufacturing Example 24: 2-Chloro-4-fluoro-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine The title compound (950 mg) was prepared as a solid in the same manner as in Preparation Example 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] Manufacturing Example 25: 1-(4-(4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one Step 1: tert-butyl 4-(4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-carboxylate The title compound (3.20 g) was prepared as a solid in the same manner as in Preparation Example 18, except that tert-butyl 4-(4-ethynylpyrazole-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-fluoropyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one The tert-butyl 4-(4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-carboxylate (1.00 g, 2.470 mmol) prepared in Step 1 was dissolved in 4.0 M HCl (10 mL) in 1,4-dioxane and stirred overnight at 60°C. After concentrating the reaction mixture, 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 obtain 1-(4-(4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one (820 mg) as a yellow solid. MS (ESI) m / z = 347.0 (M+H) +

[0794] Manufacturing Example 26: 2-(4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)-N,N-dimethylethane-1-amine Step 1: 2-(4-ethynyl-1H-pyrazole-1-yl)-N,N-dimethylethane-1-amine A DMA (40 mL) suspension of 4-ethynyl-1H-pyrazole (400 mg, 4.343 mmol), 2-iodo-N,N-dimethylethane-1-amine HCl (1.33 g, 5.646 mmol), and Cs2CO3 (4.25 g, 13.030 mmol) was stirred overnight at 80°C. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-15%) to obtain 2-(4-ethynyl-1H-pyrazole-1-yl)-N,N-dimethylethane-1-amine (545 mg) as a yellow oil. MS (ESI) m / z = 164.1 (M+H) + Step 2: 2-(4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)-N,N-dimethylethane-1-amine The title compound (544 mg) was prepared as an oil in the same manner as in Preparation Example 18, except that 2-(4-ethynyl-1H-pyrazole-1-yl)-N,N-dimethylethane-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] Manufacturing Example 27: 3-(4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)-N,N-dimethylpropane-1-amine Step 1: 3-(4-ethynyl-1H-pyrazole-1-yl)-N,N-dimethylpropane-1-amine The title compound (583 mg) was prepared as an oil in the same manner as in Step 1 of Preparation Example 26, except that 3-chloro-N,N-dimethylpropan-1-amine HCl (892 mg, 5.646 mmol) was used instead of 2-iodo-N,N-dimethylethane-1-amine HCl. MS (ESI) m / z = 178.2 (M+H) + Step 2: 3-(4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)-N,N-dimethylpropane-1-amine The title compound (577 mg) was prepared as a solid in the same manner as in Preparation Example 18, except that 3-(4-ethynyl-1H-pyrazole-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] Manufacturing Example 28: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine-4-yl)piperidine-4-one Step 1: 1-(2-chloro-5-((1-methyl-1H-pyrazole-3-yl)ethinyl)pyridine-4-yl)piperidine-4-one A DMA (7 mL) suspension of 2-chloro-4-fluoro-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine (300 mg, 1.273 mmol), piperidine-4-one HCl hydrate (293 mg, 1.91 mmol), and DIPEA (0.67 mL, 3.819 mmol), prepared in Preparation Example 24, was stirred at 50°C for 3 hours. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-5%) to obtain 1-(2-chloro-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine-4-yl)piperidine-4-one (340 mg) as a yellow solid. MS (ESI) m / z = 315.0 (M+H) + Step 2: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-3-yl)ethinyl)pyridine-4-yl)piperidine-4-one The title compound (129 mg) was prepared as a solid in the same manner as in Step 3 of Preparation Example 17, except that 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-one (330 mg, 1.048 mmol) prepared in Step 1 was used instead of tert-butyl (1-(2-chloro-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine-4-yl)piperidine-4-one (330 mg, 1.048 mmol) prepared in Step 1. MS (ESI) m / z = 544.0 (M+H) +

[0797] Production Example 29: (1-(2-chloro-5-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol Step 1: tert-butyl 3-((6-chloro-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-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 Example 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-iodopyridine-4-yl)-4-methylpiperidine-4-yl)methanol (400 mg, 1.091 mmol) prepared in Preparation Example 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]pyrazine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol A 20% TFA solution (5 mL) of tert-butyl 3-((6-chloro-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate (800 mg, 1.646 mmol) prepared in Step 1 was stirred at room temperature. After concentrating the reaction mixture, the residue was quenched with saturated NaHCO3 solution, extracted with DCM, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-20%) to obtain (1-(2-chloro-5-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol (480 mg) as an off-white solid. MS (ESI) m / z = 400.2 (M+H) +

[0798] Manufacturing example 30: 4-(4-((6-chloro-4-fluoropyridine-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 Example 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] Manufacturing Example 31: 1-(4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)benzyl)-4-methylpiperazine The title compound (1.49 g) was prepared as a solid in the same manner as in Preparation Example 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] Manufacturing example 32: 4-(3-(6-chloro-4-fluoropyridine-3-yl)prop-2-in-1-yl)morpholine The title compound (1169 mg) was prepared as a solid in the same manner as in Preparation Example 18, except that 4-(2-propyn-1-yl)morpholine (668 mg, 5.341 mmol) was used instead of 4-ethinyl-1-methylpyrazole. MS (ESI) m / z = 255.0 (M+H) +

[0801] Manufacturing Example 33: 1-((6-chloro-4-fluoropyridine-3-yl)ethynyl)cyclohexane-1-ol The title compound (505 mg) was prepared as an off-white solid in the same manner as in Preparation Example 18, except that 1-ethynylcyclohexane-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] Manufacturing example 34: 1-((6-chloro-4-fluoropyridine-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 Example 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] Manufacturing Example 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 Example 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] Manufacturing Example 36: 2-Chloro-4-fluoro-5-((1-methylpyrrolidine-3-yl)ethynyl)pyridine The title compound (131 mg) was prepared as an off-white solid in the same manner as in Preparation Example 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] Manufacturing example 37: 4-((5-((6-chloro-4-fluoropyridine-3-yl)ethinyl)thiophen-2-yl)methyl)morpholine The title compound (261 mg) was prepared as an off-white solid in the same manner as in Preparation Example 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] Manufacturing example 38: 4-((6-((6-chloro-4-fluoropyridine-3-yl)ethynyl)pyridine-3-yl)methyl)morpholine Step 1: 4-((6-ethynylpyridine-3-yl)methyl)morpholine The 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 minutes. NaBH(OAc)3 (2.42 g, 11.439 mmol) was added to the reaction mixture and stirred overnight at room temperature. A saturated NaHCO3 solution was added to the reaction mixture, extracted with DCM, washed with water, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-80%) to obtain 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-fluoropyridine-3-yl)ethynyl)pyridine-3-yl)methyl)morpholine The title compound (466 mg) was prepared as an off-white solid in the same manner as in Preparation Example 18, except that 4-((6-ethynylpyridine-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] Manufacturing example 39: 4-((5-((6-chloro-4-fluoropyridine-3-yl)ethynyl)pyridine-2-yl)methyl)morpholine Step 1: 4-((5-ethynylpyridine-2-yl)methyl)morpholine The title compound (1.22 g) was prepared as an off-white solid in the same manner as in Step 1 of Preparation Example 38, except that 5-ethynylpicolinealdehyde (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-fluoropyridine-3-yl)ethynyl)pyridine-2-yl)methyl)morpholine The title compound (658 mg) was prepared as an off-white solid in the same manner as in Preparation Example 18, except that 4-((5-ethynylpyridine-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] Manufacturing example 40: 4-((4-((6-chloro-4-fluoropyridine-3-yl)ethinyl)thiazole-2-yl)methyl)morpholine Step 1: 4-((4-ethinylthiazol-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 Example 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-fluoropyridine-3-yl)ethinyl)thiazole-2-yl)methyl)morpholine The title compound (491 mg) was prepared as an off-white solid in the same manner as in Preparation Example 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] Manufacturing Example 41: 4-((2-((6-chloro-4-fluoropyridine-3-yl)ethynyl)pyrimidine-5-yl)methyl)morpholine Step 1: 4-((2-ethynylpyrimidine-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 Example 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-fluoropyridine-3-yl)ethinyl)pyrimidine-5-yl)methyl)morpholine The title compound (558 mg) was prepared as an off-white solid in the same manner as in Preparation Example 18, except that 4-((2-ethynylpyrimidine-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] Manufacturing example 42: 4-((6-chloro-4-fluoropyridine-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 Example 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] Manufacturing Example 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 Example 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] Manufacturing Example 44: 5-Bromo-2-chloro-N-isopropylpyridine-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 Cs2CO3 (2.05 g, 6.283 mmol) in DMF (5 mL) was stirred at 100°C for 5 hours. The reaction mixture was cooled to room temperature, diluted with DCM, washed with water, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-50%) to obtain 5-bromo-2-chloro-N-isopropylpyridine-4-amine (305 mg) as a pale yellow liquid. MS (ESI) m / z = 250.9 (M+H) +

[0813] Manufacturing Example 45: (1s,4s)-4-((2-chloro-5-iodopyridine-4-yl)amino)-1-methylcyclohexane-1-ol The title compound (1.33 g) was prepared as a pale yellow liquid in the same manner as in Preparation Example 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] Manufacturing Example 46: 2-Chloro-4-fluoro-5-(thiophene-3-ylethinyl)pyridine The title compound (715 mg) was prepared as a pale yellow solid in the same manner as in Preparation Example 18, except that 3-ethinylthiophene (462 mg, 4.273 mmol) was used instead of 4-ethinyl-1-methylpyrazole. MS (ESI) m / z = 237.9 (M+H) +

[0815] Manufacturing Example 47: 5-Bromo-2-chloro-4-(1-cyclopropylpyrazole-4-yl)pyridine The reaction mixture of 5-bromo-2-chloro-4-iodopyridine (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)Cl2 (256 mg, 0.314 mmol), and 2M K2CO3 solution (9.42 mL) in 1,4-dioxane (20 mL) was stirred at 90°C for 3 hours. The reaction mixture was cooled, diluted with DCM, washed with water, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-20%) to obtain 5-bromo-2-chloro-4-(1-methylpyrazole-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] Manufacturing Example 48: 5-Bromo-2-chloro-4-(1-methylpyrazole-4-yl)pyridine The title compound (1.3 g) was prepared as an off-white solid in the same manner as in Preparation Example 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] Manufacturing Example 49: 4-(4-aminopyrimidine-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), the complex of [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) and 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) were added. The reaction mixture was stirred at 90°C for 3 hours. 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 obtain 4-(4-aminopyrimidine-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] Manufacturing Example 50: 4-(4-aminopyrimidine-2-yl)-N,N,3-trimethyl-1H-pyrazole-1-sulfonamide The title compound (325 mg) was prepared as a white solid in the same manner as in Preparation Example 49, except that (1-(N,N-dimethylsulfamoyl)-3-methyl-1H-pyrazole-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. MS (ESI) m / z = 283.2 (M+H) +

[0819] Manufacturing Example 51: 2-Chloro-5-((1-cyclopropyl-1H-pyrazole-4-yl)ethynyl)-4-fluoropyridine The title compound (400 mg) was prepared in liquid form in the same manner as in Preparation Example 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] Manufacturing Example 52: 2-Chloro-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-fluoropyridine The title compound (400 mg) was prepared in liquid form in the same manner as in Preparation Example 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] Manufacturing Example 53: (1-(2-chloro-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-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-iodopyridine-4-yl)-4-methylpiperidine-4-yl)methanol (150 mg, 0.409 mmol) and 4-ethynyl-1-(trifluoromethyl)-1H-pyrazole (72.05 mg, 0.45 mmol) prepared in Preparation Example 12 were used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperidine-4-yl)methanol (150 mg, 0.409 mmol) and 4-ethynyl-1-(trifluoromethyl)-1H-pyrazole (72.05 mg, 0.45 mmol) prepared in Preparation Example 12. MS (ESI) m / z = 399.0 (M+H) +

[0822] Manufacturing Example 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), PdCl2(PPh3)2 (182 mg, 0.260 mmol), and CuI (198 mg, 1.040 mmol) was packed with nitrogen gas for 10 minutes. After adding DMF (30 mL) and TEA (1.45 mL, 10.403 mmol), the reaction mixture was stirred overnight at 50°C. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-40%) to obtain 2-chloro-4-fluoro-5-((3-methyloxetane-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] Manufacturing example 55: 1-((6-chloro-4-fluoropyridine-3-yl)ethynyl)cyclobutan-1-ol The title compound (476 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing Example 56: 2-Chloro-4-fluoro-5-(oxetane-3-ylethynyl)pyridine The title compound (712 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing example 57: 3-((6-chloro-4-fluoropyridine-3-yl)ethinyl)oxetan-3-ol The title compound (674 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing Example 58: 3-((6-chloro-4-fluoropyridine-3-yl)ethynyl)tetrahydrofuran-3-ol The title compound (712 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing example 59: 3-((6-chloro-4-fluoropyridine-3-yl)ethynyl)tetrahydro-2H-pyran-3-ol The title compound (310 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing Example 60: 2-Chloro-4-fluoro-5-((1-methylcyclopropyl)ethynyl)pyridine The title compound (1105 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing Example 61: 2-Chloro-4-fluoro-5-((tetrahydrofuran-2-yl)ethynyl)pyridine The title compound (789 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing Example 62: 2-Chloro-4-fluoro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine The title compound (437 mg) was prepared as a solid, in the same manner as in Preparation Example 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] Manufacturing Example 63: (S)-1-(1-(2-chloro-5-iodopyridine-4-yl)piperidine-3-yl)-N,N-dimethylmethaneamine The title compound (1059 mg) was prepared as a solid in the same manner as in Preparation Example 2, except that (R)-N,N-dimethyl-1-(piperidine-3-yl)methaneamine 2HCl (580 mg, 4.079 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 380.0 (M+H) +

[0832] Manufacturing Example 64: 2-(1-(2-chloro-5-iodopyridine-4-yl)piperidine-3-yl)-N,N-dimethylethane-1-amine The title compound (1318 mg) was prepared as a solid in the same manner as in Preparation Example 2, except that N,N-dimethyl-2-(piperidine-3-yl)ethane-1-amine 2HCl (934 mg, 4.079 mmol) was used instead of 4-hydroxypiperidine. MS (ESI) m / z = 394.0 (M+H) +

[0833] Manufacturing example 65: 2-Chloro-4-fluoro-5-((1-(methylsulfonyl)piperidine-4-yl)ethynyl)pyridine Step 1: tert-butyl 4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)piperidine-1-carboxylate The title compound (9500 mg) was prepared in solid form in the same manner as in Preparation Example 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-(piperidine-4-ylethinyl)pyridine hydrochloride The tert-butyl 4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)piperidine-1-carboxylate (9.50 g, 28.04 mmol) prepared in Step 1 was dissolved in 4.0 M HCl (26.8 mL) in 1,4-dioxane and stirred at room temperature for 2 hours. After concentrating the reaction mixture, the residue was dissolved in ELISA (20 mL). The reaction mixture was concentrated again. The crude product was pulverized with diethyl ether to obtain 2-chloro-4-fluoro-5-(piperidine-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)piperidine-4-yl)ethynyl)pyridine To a 10 mL solution of 2-chloro-4-fluoro-5-(piperidine-4-ylethynyl)pyridine hydrochloride (750 mg, 3.140 mmol) prepared in Step 2, methanesulfonyl chloride (0.27 mL, 3.46 mmol) and TEA (1.31 mL, 9.43 mmol) were added. The reaction mixture was stirred overnight at room temperature. After adding water, the reaction mixture was extracted with DCM. The combined organic layer was washed with brine, dried over MgSO4, and concentrated. The crude product was purified by column chromatography (EA / n-Hex = 0-100%) to obtain 2-chloro-4-fluoro-5-((1-(methylsulfonyl)piperidine-4-yl)ethynyl)pyridine (606 mg) as a yellow solid. MS (ESI) m / z = 317.0 (M+H) +

[0834] Manufacturing Example 66: 2-Chloro-5-((1-(cyclopropylsulfonyl)piperidine-4-yl)ethynyl)-4-fluoropyridine The title compound (853 mg) was prepared as a solid, in the same manner as in step 3 of Preparation Example 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] Manufacturing Example 67: 2-Chloro-5-((1-(cyclopropylsulfonyl)pyrrolidine-3-yl)ethynyl)-4-fluoropyridine Step 1: tert-butyl 3-((6-chloro-4-fluoropyridine-3-yl)ethynyl)pyrrolidine-1-carboxylate The title compound (8730 mg) was prepared in solid form in the same manner as in Preparation Example 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-(Pyrrolidine-3-ylethinyl)pyridine hydrochloride The title compound (6450 mg) was prepared as a white solid in the same manner as in Step 2 of Preparation Example 65, except that tert-butyl 3-((6-chloro-4-fluoropyridine-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-fluoropyridine-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)pyrrolidine-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 Example 65, except that 2-chloro-4-fluoro-5-(pyrrolidine-3-ylethynyl)pyridine hydrochloride (760 mg, 3.38 mmol) and cyclopropanesulfonyl chloride (0.38 mL, 3.72 mmol) prepared in Step 2 were used instead of 2-chloro-4-fluoro-5-(piperidine-4-ylethynyl)pyridine hydrochloride and methanesulfonyl chloride. MS (ESI) m / z = 329.0 (M+H) +

[0836] Manufacturing Example 68: 2-Chloro-4-fluoro-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine The title compound (1920 mg) was prepared as a solid, in the same manner as in step 3 of Preparation Example 67, except that methanesulfonyl chloride (0.65 mL, 8.31 mmol) was used 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] Manufacturing Example 69: 1-(3-((6-chloro-4-fluoropyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one The title compound (1248 mg) was prepared in solid form in the same manner as in Preparation Example 54, except that 1-(3-ethynylpyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one (1000 mg, 5.23 mmol) was used instead of 3-ethynyl-3-methyloxetane. MS (ESI) m / z = 321.0 (M+H) +

[0838] Manufacturing example 70: 2-Chloro-4-fluoro-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine The title compound (1540 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing Example 71: 5-((7-Oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-chloro-4-fluoropyridine The title compound (1490 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing example 72: 3-((6-chloro-4-fluoropyridine-3-yl)ethinyl)tetrahydrothiophene 1,1-dioxide The title compound (1107 mg) was prepared in solid form in the same manner as in Preparation Example 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] Manufacturing Example 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 Example 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] Manufacturing Example 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 Example 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] Manufacturing Example 75: (4-((6-chloro-4-fluoropyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone The title compound (1121 mg) was prepared in solid form in the same manner as in Preparation Example 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-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-methylpiperazine-1-yl)pyridine-2-yl)pyrimidine-4-amine Step 1: 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine A DMA (7 mL) 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) was stirred overnight at 100°C. After cooling the reaction mixture, it 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 obtain 1-(2-chloro-5-iodopyridine-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-pyrazole-4-yl)ethinyl)pyridine-4-yl)-4-methylpiperazine The mixture of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine (290 mg, 0.859 mmol), 4-ethinyl-1-methylpyrazole (109.4 mg, 1.031 mmol), PdCl2(PPh3)2 (30.15 mg, 0.043 mmol), and CuI (32 mg, 0.172 mmol) prepared in Step 1 was filled with nitrogen gas for 10 minutes. After adding DMF (6 mL) and TEA (0.24 mL, 1.718 mmol), the reaction mixture was stirred at 50°C for 1 hour. The reaction mixture was cooled, diluted with EA, washed with water, dried over MgSO4, and then concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-10%) to obtain 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperazine (114 mg) as a yellow solid. MS (ESI) m / z = 316.1 (M+H) + Step 3: 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-methylpiperazine-1-yl)pyridine-2-yl)pyrimidine-4-amine A suspension of 2-(1-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-amine (111 mg, 0.418 mmol), 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperazine (110 mg, 0.348 mmol) prepared in step 2, Cs2CO3 (227 mg, 0.697 mmol), XPhos (33 mg, 0.070 mmol), and Pd2(dba)3 (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 then concentrated. The crude product was purified by column chromatography (MeOH / DCM = 0-20%) to obtain 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-methylpiperazine-1-yl)pyridine-2-yl)pyrimidine-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-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-2,4-diamine Step 1: 2-Chloro-N-cyclohexyl-5-iodopyridine-4-amine The title compound (176 mg) was prepared as a solid in the same manner as in 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-pyrazole-4-yl)ethynyl)pyridine-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-iodopyridine-4-amine (176 mg, 0.523 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 315.0 (M+H) + Step 3: N 4 -Cyclohexyl-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)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-pyrazole-4-yl)ethynyl)pyridine-4-amine (88 mg, 0.280 mmol) prepared in step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-amine)-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-pyrazole-4-yl)-N-(4-(4-(ethylsulfonyl)piperazine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine Step 1: 1-(2-chloro-5-iodopyridine-4-yl)-4-(ethylsulfonyl)piperazine The title compound (115 mg) was prepared as a solid in the same manner as in 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-pyrazole-4-yl)ethinyl)pyridine-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-iodopyridine-4-yl)-4-(ethylsulfonyl)piperazine (115 mg, 0.277 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 394.0 (M+H) + Step 3: 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(ethylsulfonyl)piperazine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-(ethylsulfonyl)piperazine (100 mg, 0.254 mmol) prepared in step 2 was used instead of. 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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)butan-1-ol Step 1: (R)-3-((2-chloro-5-iodopyridine-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-pyrazole-4-yl)ethinyl)pyridine-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-iodopyridine-4-yl)amino)butan-1-ol (228 mg, 0.698 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 305.1 (M+H) + Step 3: (R)-3-((2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-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-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)-2-methylbutan-2-ol Step 1: (S)-3-((2-chloro-5-iodopyridine-4-yl)amino)-2-methylbutan-2-ol The title compound (429 mg) was prepared as a solid in the same manner as in 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-pyrazole-4-yl)ethinyl)pyridine-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-iodopyridine-4-yl)amino)-2-methylbutan-2-ol (350 mg, 1.028 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 319.0 (M+H) + Step 3: (S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)-2-methylbutan-2-ol The title compound (75 mg) was prepared in solid form in the same manner as in step 3 of Example 1, except that (S)-3-((2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-2-methylbutan-2-ol (290 mg, 0.910 mmol) prepared in step 2. 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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-ol Step 1: 1-(2-chloro-5-iodopyridine-4-yl)piperidine-3-ol The title compound (320 mg) was prepared as a solid in the same manner as in 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-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-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-iodopyridine-4-yl)piperidine-3-ol (208 mg, 0.614 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 317.1 (M+H) + Step 3: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-ol (170 mg, 0.537 mmol) prepared in step 2 was used instead of-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-one Step 1: 1-(2-chloro-5-iodopyridine-4-yl)piperidine-4-one The title compound (1.54 g) was prepared as a solid in the same manner as in Step 1 of Example 1, except that piperidine-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-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-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-iodopyridine-4-yl)piperidine-4-one (1.00 g, 2.971 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 315.0 (M+H) + Step 3: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-one (700 mg, 2.224 mmol) prepared in step 2 was used instead of-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-pyrazole-4-yl)-N-(4-(4-fluoropiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine Step 1: 2-Chloro-4-(4-fluoropiperidine-1-yl)-5-iodopyridine The title compound (686 mg) was prepared as a solid in the same manner as in 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-fluoropiperidine-1-yl)-5-((1-methyl-1H-pyrazole-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-fluoropiperidine-1-yl)-5-iodopyridine (220 mg, 0.646 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 319.0 (M+H) + Step 3: 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoropiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-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-fluoropiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine (163 mg, 0.511 mmol) prepared in step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol Step 1: (1-(2-chloro-5-iodopyridine-4-yl)piperidine-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-piperidine methanol (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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-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-iodopyridine-4-yl)piperidine-3-yl)methanol (240 mg, 0.681 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 3: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol (153 mg, 0.463 mmol) prepared in step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol Step 1: 1-(1-(2-chloro-5-iodopyridine-4-yl)piperidine-4-yl)ethane-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-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)ethane-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-iodopyridine-4-yl)piperidine-4-yl)ethane-1-ol (300 mg, 0.818 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 345.1 (M+H) + Step 3: 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)ethane-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol (220 mg, 0.638 mmol) prepared in step 2 was used instead of -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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)propan-2-ol Step 1: 2-(1-(2-chloro-5-iodopyridine-4-yl)piperidine-4-yl)propan-2-ol The title compound (748 mg) was prepared as a solid in the same manner as in Step 1 of Example 1, except that 2-(piperidine-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-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-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-iodopyridine-4-yl)piperidine-4-yl)propan-2-ol (300 mg, 0.788 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 359.1 (M+H) + Step 3: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)propan-2-ol (236 mg, 0.657 mmol) prepared in step 2 was used instead of -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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol Step 1: (1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperidine-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-methylpiperidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-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-iodopyridine-4-yl)-4-methylpiperidine-4-yl)methanol (300 mg, 0.818 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 345.1 (M+H) + Step 3: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol (220 mg, 0.638 mmol) prepared in step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol Step 1: 7-(2-chloro-5-iodopyridine-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-pyrazole-4-yl)ethinyl)pyridine-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-iodopyridine-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-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 371.2 (M+H) + Step 3: 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-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-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-2-methylpropane-1-ol Step 1: 2-(1-(2-chloro-5-iodopyridine-4-yl)piperidine-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-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-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-iodopyridine-4-yl)piperidine-4-yl)-2-methylpropan-1-ol (300 mg, 0.760 mmol) prepared in Step 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 373.1 (M+H) + Step 3: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-2-methylpropane-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-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-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)-N-(4-(4-methoxypiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine Step 1: 2-Chloro-5-iodo-4-(4-methoxypiperidine-1-yl)pyridine The title compound (763 mg) was prepared as a solid, in the same manner as in 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-methoxypiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)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-methoxypiperidine-1-yl)pyridine (500 mg, 1.418 mmol) was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 3: 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-methoxypiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-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-methoxypiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine (330 mg, 0.998 mmol) prepared in step 2 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperazine-1-yl)ethane-1-ol Step 1: 2-(4-(2-chloro-5-iodopyridine-4-yl)piperazine-1-yl)ethane-1-ol The title compound (443 mg) was prepared as a solid in the same manner as in Step 1 of Example 1, except that 2-(piperazin-1-yl)ethane-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-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperazine-1-yl)ethane-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-iodopyridine-4-yl)piperazine-1-yl)ethane-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-iodopyridine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperazine-1-yl)ethane-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperazine-1-yl)ethane-1-ol (200 mg, 0.529 mmol) prepared in step 2 was used instead of 1-4-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol Step 1: 2-(1-(2-chloro-5-iodopyridine-4-yl)piperidine-4-yl)ethane-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-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-iodopyridine-4-yl)piperidine-4-yl)ethane-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-iodopyridine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)ethane-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol (86 mg, 0.227 mmol) prepared in step 2 was used instead of -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-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine Step 1: 2-Chloro-N-isopropyl-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-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-iodopyridine-4-amine (285 mg, 0.961 mmol) was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 275.1 (M+H) + Step 2: N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-methyl-1H-pyrazole-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-pyrazole-4-yl)ethynyl)pyridine-4-amine (107 mg, 0.39 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-amine)-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-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-Isopropyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine Step 1: 2-Chloro-N-isopropyl-5-((1-isopropyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-amine The title compound (85 mg) was prepared as a solid in the same manner as in step 2 of Example 1, except that 4-ethynyl-1-isopropylpyrazole (95 mg, 0.708 mmol) and 2-chloro-5-iodo-N-isopropylpyridine-4-amine (140 mg, 0.472 mmol) were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 303.1 (M+H) + Step 2: N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-Isopropyl-1H-pyrazole-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-pyrazole-4-yl)ethynyl)pyridine-4-amine (110 mg, 0.362 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-amine)-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-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine Step 1: 2-Chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N-isopropylpyridine-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-(2-fluoroethyl)pyrazole (98 mg, 0.708 mmol) and 2-chloro-5-iodo-N-isopropylpyridine-4-amine (140 mg, 0.472 mmol) were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 307.1 (M+H) + Step 2: N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-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-pyrazole-4-yl)ethynyl)-N-isopropylpyridine-4-amine (111 mg, 0.362 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-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-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(pyridine-3-ylethinyl)pyridine-2,4-diamine Step 1: 2-Chloro-N-isopropyl-5-(pyridine-3-ylethynyl)pyridine-4-amine The title compound (45 mg) was prepared as a solid in the same manner as in step 2 of Example 1, except that 3-ethynylpyridine (73 mg, 0.708 mmol) and 2-chloro-5-iodopyridine-4-amine (140 mg, 0.472 mmol) were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 272.1 (M+H) + Step 2: N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(pyridine-3-ylethinyl)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-(pyridine-3-ylethynyl)pyridine-4-amine (98 mg, 0.362 mmol) was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(4-methoxybuto-1-in-1-yl)pyridine-2,4-diamine Step 1: 2-Chloro-N-isopropyl-5-(4-methoxybuto-1-in-1-yl)pyridine-4-amine The title compound (109 mg) was prepared as a solid in the same manner as in step 2 of Example 1, except that 4-methoxybuto-1-yin (102 mg, 1.214 mmol) and 2-chloro-5-iodo-N-isopropylpyridine-4-amine (240 mg, 0.809 mmol) were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 253.1 (M+H) + Step 2: N 2-(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(4-methoxybuto-1-in-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-methoxybuto-1-inyl)pyridine-4-amine (91 mg, 0.362 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine Step 1: 2-Chloro-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N-isopropylpyridine-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-isopropylpyridine-4-amine (220 mg, 0.742 mmol) were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 325.1 (M+H) + Step 2: N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-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-pyrazole-4-yl)ethynyl)-N-isopropylpyridine-4-amine (160 mg, 0.493 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-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-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-2,4-diamine Step 1: N-(sec-butyl)-2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-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-iodopyridine-4-amine (140 mg, 0.451 mmol) prepared in Preparation Example 1 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 289.0 (M+H) + Step 2: N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)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-pyrazole-4-yl)ethynyl)pyridine-4-amine (104 mg, 0.362 mmol) prepared in step 1 was used instead of 1-(-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-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-isopropyl-1H-pyrazole-4-yl)ethinyl)pyridine-2,4-diamine Step 1: N-(sec-butyl)-2-chloro-5-((1-isopropyl-1H-pyrazole-4-yl)ethynyl)pyridine-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-iodopyridine-4-amine (190 mg, 0.612 mmol) and 4-ethynyl-1-isopropylpyrazole (123 mg, 0.918 mmol) prepared in Preparation Example 1 were used instead of 1-(2-chloro-5-iodopyridine-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-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-isopropyl-1H-pyrazole-4-yl)ethinyl)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-pyrazole-4-yl)ethynyl)pyridine-4-amine (115 mg, 0.362 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-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-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine Step 1: N-(sec-butyl)-2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-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-iodopyridine-4-amine (190 mg, 0.612 mmol) and 4-ethynyl-1-(2-fluoroethyl)pyrazole (127 mg, 0.918 mmol) prepared in Preparation Example 1 were used instead of 1-(2-chloro-5-iodopyridine-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-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-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-pyrazole-4-yl)ethynyl)pyridine-4-amine (116 mg, 0.362 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-amine (116 mg, 0.362 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-ol Step 1: 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-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-iodopyridine-4-yl)piperidine-4-ol (460 mg, 1.359 mmol) prepared in Preparation Example 2 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 317.0 (M+H) + Step 2: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-ol (200 mg, 0.631 mmol) prepared in step 1 was used instead of-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-ol Step 1: 1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-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-(2-fluoroethyl)pyrazole (67 mg, 0.487 mmol) and 1-(2-chloro-5-iodopyridine-4-yl)piperidine-4-ol (150 mg, 0.443 mmol) prepared in Preparation Example 2 were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 349.2 (M+H) + Step 2: 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-ol (80 mg, 0.229 mmol) prepared in step 1 was used instead of. 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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol Step 1: (1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-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-iodopyridine-4-yl)piperidine-4-yl)methanol (150 mg, 0.425 mmol) prepared in Preparation Example 3 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 2: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol (78 mg, 0.235 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol (78 mg, 0.235 mmol) prepared in step 1. 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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol Step 1: (1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-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-iodopyridine-4-yl)piperidine-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-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 363.1 (M+H) + Step 2: (1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol (220 mg, 0.606 mmol) prepared in step 1 was used instead of . 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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-3-ol Step 1: (R)-1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-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-iodopyridine-4-yl)pyrrolidine-3-ol (200 mg, 0.616 mmol) prepared in Preparation Example 4 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 317.1 (M+H) + Step 2: (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-ol (118 mg, 0.390 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-ol (118 mg, 0.390 mmol) prepared in step 1. 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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-3-ol Step 1: (R)-1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-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-(2-fluoroethyl)pyrazole (112 mg, 0.813 mmol) and (R)-1-(2-chloro-5-iodopyridine-4-yl)pyrrolidine-3-ol (240 mg, 0.739 mmol) prepared in Preparation Example 4 were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 335.1 (M+H) + Step 2: (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidin-3-ol (200 mg, 0.597 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-ol (200 mg, 0.597 mmol) prepared in step 1. 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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-yl)methanol Step 1: (1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-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-iodopyridine-4-yl)pyrrolidine-3-yl)methanol (200 mg, 0.591 mmol) prepared in Preparation Example 5 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 303.1 (M+H) + Step 2: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-yl)methanol (108 mg, 0.342 mmol) prepared in step 1 was used instead of -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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-yl)methanol Step 1: (1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-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-(2-fluoroethyl)pyrazole (90 mg, 0.650 mmol) and (1-(2-chloro-5-iodopyridine-4-yl)pyrrolidine-3-yl)methanol (200 mg, 0.591 mmol) prepared in Preparation Example 5 were used instead of 4-ethynyl-1-methylpyrazole and 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 349.1 (M+H) + Step 2: (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-yl)methanol (143 mg, 0.410 mmol) prepared in step 1 was used instead of rolidine-3-yl)methanol (143 mg, 0.410 mmol) prepared in step 1. 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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-3-yl)propan-2-ol Step 1: 2-(1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-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-iodopyridine-4-yl)azetidine-3-yl)propan-2-ol (261 mg, 0.740 mmol) prepared in Preparation Example 6 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 2: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)azetidine-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-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-3-yl)propan-2-ol Step 1: 2-(1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-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-iodopyridine-4-yl)azetidine-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-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 363.1 (M+H) + Step 2: 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)azetidine-3-yl)propan-2-ol (300 mg, 0.827 mmol) prepared in step 1 was used instead of -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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)(methyl)amino)ethane-1-ol Step 1: 2-((2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)(methyl)amino)ethane-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-iodopyridine-4-yl)(methyl)amino)ethane-1-ol (280 mg, 0.896 mmol) prepared in Preparation Example 7 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 291.1 (M+H) + Step 2: 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)(methyl)amino)ethane-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)(methyl)amino)ethane-1-ol (94 mg, 0.322 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)(methyl)amino)ethane-1-ol Step 1: 2-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)(methyl)amino)ethane-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-(2-fluoroethyl)pyrazole (136 mg, 0.985 mmol) and 2-((2-chloro-5-iodopyridine-4-yl)(methyl)amino)ethane-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-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 323.1 (M+H) + Step 2: 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)(methyl)amino)ethane-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)(methyl)amino)ethane-1-ol (322 mg, 0.998 mmol) prepared in step 1 was used instead of 1--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-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-yl)amino)-5-(2-(1-methylpyrazole-4-yl)ethinyl)-4-pyridyl)amino)-2,2-dimethyl-propane-1-ol Step 1: 3-((2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)-2,2-dimethylpropane-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-iodopyridine-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-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 319.1 (M+H) + Step 2: 3-((2-((2-(1-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-yl)amino)-5-(2-(1-methylpyrazole-4-yl)ethinyl)-4-pyridyl)amino)-2,2-dimethyl-propane-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-2,2-dimethylpropan-1-ol (100 mg, 0.314 mmol) prepared in step 1 was used instead of 1--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-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-yl)amino)-5-(2-(1-(2-fluoroethyl)pyrazole-4-yl)ethynyl)-4-pyridyl)amino)-2,2-dimethyl-propane-1-ol Step 1: 3-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-2,2-dimethylpropane-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-iodopyridine-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-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 351.1 (M+H) + Step 2: 3-((2-((2-(1-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-yl)amino)-5-(2-(1-(2-fluoroethyl)pyrazole-4-yl)ethinyl)-4-pyridyl)amino)-2,2-dimethyl-propane-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-2,2-dimethylpropan-1-ol (130 mg, 0.371 mmol) prepared in step 1 was used instead of 1-. 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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol Step 1: (1s,4s)-4-((2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-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-iodopyridine-4-yl)amino)cyclohexane-1-ol (250 mg, 0.709 mmol) prepared in Preparation Example 9 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 2: (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol The title compound (72 mg) was prepared in solid form in the same manner as in step 3 of Example 1, except that (1s,4s)-4-((2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol (200 mg, 0.605 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol (200 mg, 0.605 mmol) prepared in step 1. 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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol Step 1: (1s,4s)-4-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-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-iodopyridine-4-yl)amino)cyclohexane-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-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 363.0 (M+H) + Step 2: (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol The title compound (86 mg) was prepared in solid form in the same manner as in step 3 of Example 1, except that (1s,4s)-4-((2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol (200 mg, 0.551 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol (200 mg, 0.551 mmol) prepared in step 1. 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-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol Step 1: (1S,3S)-3-((2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-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-iodopyridine-4-yl)amino)cyclohexane-1-ol (200 mg, 0.567 mmol) prepared in Preparation Example 10 was used instead of 1-(2-chloro-5-iodopyridine-4-yl)-4-methylpiperazine. MS (ESI) m / z = 331.1 (M+H) + Step 2: (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-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-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol (190 mg, 0.574 mmol) prepared in step 1 was used instead of 1-(2-chloro-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-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 ...

Claims

1. Compounds of chemical formula (I) or pharmaceutically acceptable salts thereof: 【Chemistry 1】 During the ceremony, R １ teeth, -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 on 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 Alkenil; -C(O)NHC １－６ Alkyl; -C(O)N(C １－６ Alkyl) 2 ; -C(O)-4 to 7-membered heterocyclyl; -NHCs are optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogens. １－６ Alkyl; -N(C) is optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogens. １－６ Alkyl) 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 aryls; 4-8 membered heterocyclines; and 5-10 membered heteroaryls, R １Ａ teeth, 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 member 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 A C12C １－６ Alkyl; OH, halogens, and -N(C) １－６ Alkyl) 2 C is optionally substituted with one or more substituents selected from the group consisting of the following: ３－６ Cycloalkyl; -C(O)C is optionally substituted with one or more substituents selected from the group consisting of OH and halogens. １－６ Alkyl; -C(O)N(C １－６ Alkyl) ２ ; -C(O)-4 to 7-membered heterocyclines optionally substituted with one or more substituents selected from the group consisting of OH and halogens; -NHCs are arbitrarily substituted with 4- to 7-membered heterocyclines. 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 C is arbitrarily substituted with １－６ Alkyl, C ３－６ Cycloalkyl, C １－６ Haloalkyl, -C(O)C １－６ 4- to 11-membered heterocyclines that are optionally or independently substituted with one or more substituents selected from the group consisting of alkyl groups and 4- to 7-membered heterocyclines. Independently selected from the group consisting of, m is an integer between 0 and 2. R ２ -N(C) is arbitrarily substituted with one or more OH groups. 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 -XC is arbitrarily replaced with 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 between 0 and 1. o is an integer between 0 and 3. B is C ３－７ Cycloalkyl; C ６－１０ Selected from the group consisting of aryls; 4- to 12-membered heterocyclines; and 5- to 6-membered heteroaryls, R ２Ａ teeth, H; OH; halogen; OH, halogen, -NHC １－６ Alkyl, -NHC １－６ Haloalkyl, -N(C) １－６ Alkyl) ２ , 4-7 member heterocyclyl, and C １－３ C is optionally or independently substituted with one or more substituents selected from the group consisting of alkoxys. １－６ Alkyl; C is optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogens. ３－６ Cycloalkyl; C is 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 １－６ alkyl optionally or independently substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclyl; -NHCs are optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogens. ３－６ Cycloalkyl; -N(C １－６ alkyl) optionally or independently substituted with one or more substituents selected from the group consisting of OH and halogen 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; Halogens and C １－６ A 4- to 7-membered heterocycline optionally or independently substituted with one or more substituents selected from the group consisting of alkyl groups; =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 between 0 and 2. Q is a 4-7 member heterocyclyl; C ６－１０ Selected from the group consisting of aryls and 5-6 member heteroaryls, R ３Ａ H; halogen; halogen and C ３－６ C is optionally substituted with one or more substituents selected from the group consisting of cycloalkyl groups. １－６ Alkyl; C ３－６ Cycloalkyl; 4-7 member heterocycline; optionally substituted with 1-3 halogens -S(O) ２ C １－６ Alkyl; optionally substituted with one or more halogens -S(O) ２ C ３－６ Cycloalkyl; and -S(O) ２ N(C) １－６ Alkyl) ２ Independently selected from the group consisting of, R ４ These are H, halogen, and C １－６ Selected from the group consisting of alkyl groups.

2. R １ However, -H; -Si(C １－６ Alkyl) ３ ;OH, halogen, C １－３ Alkoxy, -NHC(O)C １－６ C14 is optionally or independently substituted with one or more substituents selected from the group consisting of haloalkyls, -NHC(O)-4 to 7-membered heterocyclines, -C(O)-4 to 7-membered heterocyclines, and 4 to 7-membered heterocyclines optionally or independently substituted with oxos. １－６ Alkyl; C ２－５ Alkenyl; and -A-(R １Ａ ) ｍ A compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of the following.

3. R1 is a C1-6 alkyl group which is optionally or independently substituted with one or more substituents selected from the group consisting of -NHC(O)-4 to 7-membered heterocyclines, -C(O)-4 to 7-membered heterocyclines, and 4 to 7-membered heterocyclines which are optionally or independently substituted with an oxo molecule. The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein the 4- to 7-membered heterocyclil is selected from the group consisting of morpholinil, pyrrolidinil, 1,1-dioxo-1,4-thiadinil, and oxetanil.

4. A is C ３－６ Cycloalkyl, phenyl, pyrazolyl, pyridinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyradinyl, triazolyl, thiazolyl, pyrazinyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, thienyl, pyrimidinyl, tetrahydrofuranyl, imidazolyl, pyrrolyl, pyrrolo[3,2-c]pyradinyl, oxetanyl, 7-oxabicyclo [2.2.1] A compound according to claim 1, selected from the group consisting of heptanil and 1,1-dioxothiolanil, or a pharmaceutically acceptable salt thereof.

5. R １Ａ but, 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 halogens and C １－６ A C12C １－６ Alkyl; C is optionally substituted with one or more halogens. ３－６ Cycloalkyl; -C(O)C which is optionally substituted with one or more halogens １－６ Alkyl; -C(O)N(C １－６ Alkyl) ２ ; -C(O)-4 to 7-membered heterocyclines arbitrarily substituted with one or more OH groups; -NHCs are arbitrarily substituted with 4- to 7-membered heterocyclines. 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 4- to 11-membered heterocyclines that are optionally or independently substituted with one or more substituents selected from the group consisting of alkyl groups. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of the following.

6. R1A is a C1-6 alkyl group in which R1A is optionally substituted with one or more substituents selected from the group consisting of 4- to 7-membered heterocyclines, which are optionally substituted with one or more substituents selected from the group consisting of halogens and C1-6 alkyl groups; -C(O)-4 to 7-membered heterocyclines arbitrarily substituted with one or more OH groups; -NHC1-6 alkyl groups optionally substituted with 4- to 7-membered heterocyclines; and 4- to 11-membered heterocyclines optionally or independently substituted with one or more substituents selected from the group consisting of C1-6 alkyl and -C(O)C1-6 alkyl. Selected from the group consisting of, The compound according to claim 5 or a pharmaceutically acceptable salt thereof, wherein the 4- to 7-membered heterocyclil or 4- to 11-membered heterocyclil is selected from the group consisting of tetrahydropyranil, piperidinil, azetidinil, morpholinil, piperazinil, dioxanil, tetrahydrofuranil, and oxetanil.

7. R ２ However, -N(C) is arbitrarily substituted with one or more OH groups. １－６ Alkyl) ２ -XC which is arbitrarily substituted with OH. １－６ alkyl; and -X(CH ２ ) ｎ -B-(R) ２Ａ ) ｏ A compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of the following.

8. B is C ３－６ A compound according to claim 1, selected from the group consisting of cycloalkyl;phenyl;piperazinyl, piperidinyl, 4-oxopiperidinyl, azaspiro[3.5]nonanyl, pyrrolidinyl, azetidinyl, azepanyl, 2,8-diazaspiro[4.5]decanyl, 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]decanyl, or a pharmaceutically acceptable salt thereof.

9. R ２Ａ but, H; OH; halogen; OH, halogen, -NHC １－６ Alkyl, -NHC １－６ Haloalkyl and -N(C) １－６ Alkyl) ２ C is optionally or independently substituted with one or more substituents selected from the group consisting of the following: １－６ Alkyl; C is substituted arbitrarily or independently by one or more OH groups. ３－６ Cycloalkyl; C is 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 -NHC which is optionally or independently substituted with one or more substituents selected from the group consisting of １－６ Alkyl; - NHS(O) ２ C １－６ Alkyl; -S(O) ２ C １－６ Alkyl; Halogens and C １－６ A 4- to 7-membered heterocycline optionally or independently substituted with one or more substituents selected from the group consisting of alkyl groups; =O; and C(O)C １－６ Alkyl A compound according to claim 1 or a pharmaceutically acceptable salt thereof, independently selected from the group consisting of the following.

10. R 2A is a 4- to 7-membered heterocycline which is optionally or independently substituted with one or more substituents selected from the group consisting of halogens and C1-6 alkyl groups, The compound according to claim 9 or a pharmaceutically acceptable salt thereof, wherein the 4- to 7-membered heterocyclyl is piperazinyl or azetidinyl.

11. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein Q is selected from the group consisting of pyrazolyl, pyridinyl, phenyl, and piperazinyl.

12. R ３Ａ However, halogens; C is 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 A compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of the following.

13. R ４ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein H is present.

14. (1) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-methylpiperazine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (2) N 4 -Cyclohexyl-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-2,4-diamine; (3) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(ethylsulfonyl)piperazine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (4) (R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)butan-1-ol; (5) (S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)-2-methylbutan-2-ol; (6) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol; (7) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-one; (8) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoropiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (9) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol; (10) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol; (11) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)propan-2-ol; (12) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (13) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol; (14) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-2-methylpropan-1-ol; (15) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-methoxypiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (16) 2-(4-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperazine-1-yl)ethane-1-ol; (17) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol; (18) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine; (19) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((1-Isopropyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine; (20) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine; (21) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(pyridine-3-ylethinyl)pyridine-2,4-diamine; (22) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(4-methoxybuto-1-in-1-yl)pyridine-2,4-diamine; (23) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine; (24) N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-2,4-diamine; (25) N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-isopropyl-1H-pyrazole-4-yl)ethinyl)pyridine-2,4-diamine; (26) N 4 -(sec-butyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine; (27) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol; (28) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-ol; (29) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol; (30) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol; (31) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-3-ol; (32) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)pyrrolidine-3-ol; (33) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-yl)methanol; (34) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)pyrrolidine-3-yl)methanol; (35) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-3-yl)propan-2-ol; (36) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azetidine-3-yl)propan-2-ol; (37) 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)(methyl)amino)ethane-1-ol; (38) 2-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)(methyl)amino)ethane-1-ol; (39) 3-((2-((2-(1-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-yl)amino)-5-(2-(1-methylpyrazole-4-yl)ethinyl)-4-pyridyl)amino)-2,2-dimethyl-propane-1-ol; (40) 3-((2-((2-(1-cyclopropylsulfonylpyrazole-4-yl)pyrimidine-4-yl)amino)-5-(2-(1-(2-fluoroethyl)pyrazole-4-yl)ethinyl)-4-pyridyl)amino)-2,2-dimethyl-propane-1-ol; (41) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (42) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (43) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (44) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (45) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (46) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (47) (1-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (48) (1-(5-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (49) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (50) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -(4-((dimethylamino)methyl)benzyl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine; (51) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -(4-((dimethylamino)methyl)benzyl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine; (52) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N 4 -(4-((dimethylamino)methyl)benzyl)pyridine-2,4-diamine; (53) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methyl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine; (54) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-isopropoxy-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (55) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-isopropoxypyridine-2-yl)pyrimidine-4-amine; (56) N-(4-(sec-butoxy)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (57) N-(4-(sec-butoxy)-5-((1-isopropyl-1H-pyrazole-4-yl)ethynyl)pyridin-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (58) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (59) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((1-isopropyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (60) N-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethynyl)-4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (61) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (62) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-(pyridine-3-ylethynyl)pyridine-2-yl)pyrimidine-4-amine; (63) N-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanesulfonamide; (64) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(isopropylamino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (65) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-(trifluoromethyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (66) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoro-4-(trifluoromethyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (67) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-(trifluoromethoxy)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (68) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-3,3-difluoropiperidine-4-ol; (69) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-3,3-dimethylpiperidine-4-ol; (70) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-fluoropiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (71) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(3-(trifluoromethyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (72) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-(fluoromethyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (73) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol; (74) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -(3-fluorocyclohexyl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine; (75) (1R,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (76) (1R,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (77) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azepan-4-ol; (78) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)azepan-4-yl)methanol; (79) 8-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-2,8-diazaspiro[4.5]decane-1-one; (80) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -((1s,4s)-4-((2-fluoroethyl)amino)cyclohexyl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine; (81) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol; (82) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-ol; (83) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol; (84) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol; (85) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (86) 1-(5-((5-cyclopropyl-1-methyl-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)piperidine-4-ol; (87) 2-(1-(5-((5-cyclopropyl-1-methyl-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)piperidine-4-yl)ethane-1-ol; (88) (1s,4s)-4-((5-((5-cyclopropyl-1-methyl-1H-pyrazole-4-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)cyclohexane-1-ol; (89) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-ol; (90) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol; (91) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol; (92) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (93) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-one; (94) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (95) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (96) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol; (97) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoropiperidine-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (98) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-methoxypiperidine-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (99) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol; (100) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol; (101) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (102) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (103) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (104) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol; (105) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol; (106) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (107) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (108) 1-(5-((1-(1-acetylpiperidine-4-yl)-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)piperidine-4-one; (109) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one; (110) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one; (111) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-fluoro-4-(hydroxymethyl)piperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one; (112) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-fluoropiperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one; (113) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-methoxypiperidine-1-yl)pyridine-3-yl)ethinyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one; (114) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(3-hydroxypiperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one; (115) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(3-(hydroxymethyl)piperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one; (116) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (117) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol; (118) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol; (119) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (120) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (121) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol; (122) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-yl)methanol; (123) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (124) N-(4-(4-((cyclopropylmethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (125) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(isopentylamino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (126) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2,2-difluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (127) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-((3,3,3-trifluoropropyl)amino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (128) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(3,3-difluoroazetidine-1-yl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (129) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (130) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-(methylamino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (131) 2-((1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)amino)ethane-1-ol; (132) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-methoxyethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (133) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-N 2 ,N 2 -Dimethylethane-1,2-diamine; (134) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-N 2 ,N 2 ,2-trimethylpropane-1,2-diamine; (135) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-((2,2,2-trifluoroethyl)amino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (136) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidine-1-yl)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (137) 2-((1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)amino)ethane-1-ol; (138) N 1 -(1-(2-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-N 2 ,N 2 -Dimethylethane-1,2-diamine; (139) 1-(4-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-((2-(dimethylamino)ethyl)amino)piperidine-1-yl)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)piperidine-1-yl)ethane-1-one; (140) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-3-yl)ethynyl)-4-(4-(methylamino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (141) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((2-fluoroethyl)amino)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-3-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (142) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-3-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-N 2 ,N 2 -Dimethylethane-1,2-diamine; (143) N 1 -(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)-N 2 ,N 2 -Dimethylethane-1,2-diamine; (144) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2-(dimethylamino)ethyl)-1H-pyrazole-4-yl)ethynyl)-4-(4-((2-fluoroethyl)amino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (145) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)-4-(4-((2-fluoroethyl)amino)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (146) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-methyl-4-((methylamino)methyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (147) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(1-methylpiperidine-4-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (148) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(1-methylazetidine-3-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (149) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (150) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (151) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(2,2-difluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (152) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(3-(dimethylamino)propyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol; (153) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(4-(2-(methylamino)ethyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (154) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethinyl)-4-(2,8-diazaspiro[4.5]decane-2-yl)pyridine-2-yl)pyrimidine-4-amine; (155) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethinyl)-4-(2,7-diazaspiro[3.5]nonanane-2-yl)pyridine-2-yl)pyrimidine-4-amine; (156) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-4-(2,8-diazaspiro[4.5]decane-8-yl)pyridine-2-yl)pyrimidine-4-amine; (157) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (158) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol; (159) (1R,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (160) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (161) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (162) 2-((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexyl)propan-2-ol; (163) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (164) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (165) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(3-morpholinoprop-1-in-1-yl)pyridine-4-yl)amino)cyclohexane-1-ol; (166) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(3-morpholinoprop-1-in-1-yl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol; (167) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1,2,4-triazole-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (168) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-ethylthiazole-2-yl)ethinyl)pyridine-4-yl)amino)cyclohexane-1-ol; (169) (1S,3R)-3-((5-((3-aminophenyl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)cyclohexane-1-ol; (170) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-methylpyrazine-2-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (171) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(3-(pyrrolidine-1-yl)prop-1-in-1-yl)pyridine-4-yl)amino)cyclohexane-1-ol; (172) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((2-morpholinoethyl)amino)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (173) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-((2-morpholinoethyl)amino)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (174) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridine-3-yl)ethynyl)cyclohexane-1-ol; (175) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)cyclohexane-1-ol; (176) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-hydroxycyclopentyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (177) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)cyclopentan-1-ol; (178) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (179) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (180) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylpyrrolidine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (181) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylpyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (182) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylpiperidine-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (183) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-methyltetrahydro-2H-pyran-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (184) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyridine-2-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (185) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyridine-2-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (186) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-(morpholinomethyl)pyridine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (187) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-(morpholinomethyl)pyridine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (188) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(morpholinomethyl)thiazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclohexane-1-ol; (189) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(morpholinomethyl)thiazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (190) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)thiophen-2-yl)ethinyl)pyridine-4-yl)amino)cyclohexane-1-ol; (191) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)thiophen-2-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (192) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(morpholinomethyl)thiazole-5-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (193) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidine-2-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (194) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidine-2-yl)ethinyl)pyridine-4-yl)amino)cyclohexane-1-ol; (195) 4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)tetrahydro-2H-pyran-4-ol; (196) 4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridine-3-yl)ethinyl)tetrahydro-2H-pyran-4-ol; (197) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (198) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (199) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((2-methylthiazole-4-yl)ethinyl)pyridine-2,4-diamine; (200) N 2- (2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((2-(fluoromethyl)thiazole-4-yl)ethynyl)-N 4 -Isopropylpyridine-2,4-diamine; (201) 4-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)prop-2-in-1-yl)thiomorpholine 1,1-dioxide; (202) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(3-morpholinoprop-1-in-1-yl)pyridine-2,4-diamine; (203) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-(3-(pyrrolidine-1-yl)prop-1-in-1-yl)pyridine-2,4-diamine; (204) 4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)-2-methylbuto-3-in-2-ol; (205) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((2-cyclopropylthiazole-4-yl)ethinyl)-N 4 -Isopropylpyridine-2,4-diamine; (206) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -Isopropyl-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridine-2,4-diamine; (207) N-(5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)pento-4-in-1-yl)morpholine-4-carboxamide; (208) 6-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)-1-morpholinohex-5-in-1-one; (209) N-(6-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)hex-5-in-1-yl)morpholine-4-carboxamide; (210) 7-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(isopropylamino)pyridine-3-yl)-1-morpholinohepto-6-in-1-one; (211) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methylthiazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol; (212) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(fluoromethyl)thiazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol; (213) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-imidazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-ol; (214) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-1,2,4-triazole-3-yl)ethinyl)pyridine-4-yl)piperidine-4-ol; (215) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-morpholinopyridine-3-yl)ethinyl)pyridine-4-yl)piperidine-4-ol; (216) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-imidazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclohexane-1-ol; (217) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(thiophene-3-ylethinyl)pyridine-4-yl)amino)cyclohexane-1-ol; (218) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (219) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-morpholinoethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (220) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol; (221) 2-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-hydroxy-4-methylcyclohexyl)amino)pyridine-3-yl)ethynyl)-1H-pyrazole-1-yl)-N,N-dimethylacetamide; (222) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methylthiazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclopentan-1-ol; (223) (1S,3R)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-imidazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclopentan-1-ol; (224) 3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-imidazole-4-yl)ethinyl)pyridine-4-yl)amino)-2,2-dimethylpropane-1-ol; (225) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(thiophene-3-ylethinyl)pyridine-4-yl)amino)cyclohexane-1-ol; (226) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)-5-(thiophene-3-ylethynyl)pyridine-2-yl)pyrimidine-4-amine; (227) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-morpholinopyridine-3-yl)ethinyl)pyridine-4-yl)piperidine-3-ol; (228) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(thiophene-3-ylethinyl)pyridine-4-yl)piperidine-3-ol; (229) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(thiophene-3-ylethinyl)pyridine-4-yl)-3,3-dimethylpiperidine-4-ol; (230) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(3-methyl-3-morpholinbut-1-in-1-yl)pyridine-4-yl)amino)cyclohexane-1-ol; (231) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (232) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-morpholinoethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (233) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(1-methyl-1H-pyrazole-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (234) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-(1-methyl-1H-pyrazole-4-yl)pyridine-2-yl)pyrimidine-4-amine; (235) N-(4-(1-cyclopropyl-1H-pyrazole-4-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (236) N-(4-(1-cyclopropyl-1H-pyrazole-4-yl)-5-((1-isopropyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (237) N-(4-(1-cyclopropyl-1H-pyrazole-4-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (238) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-((2-methylthiazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (239) 4-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)pyridine-3-yl)prop-2-in-1-yl)thiomorpholine 1,1-dioxide; (240) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)methoxy)-5-(3-(pyrrolidine-1-yl)prop-1-in-1-yl)pyridine-2-yl)pyrimidine-4-amine; (241) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydro-2H-pyran-3-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (242) (1-(5-((1-((1,4-dioxan-2-yl)methyl)-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (243) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-((tetrahydrofuran-3-yl)methyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (244) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (245) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(oxetan-3-yl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (246) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((trimethylsilyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (247) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-ethynylpyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (248) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-((3,3-difluoroazetidine-1-yl)methyl)-1-(2,2-difluoroethyl)-1H-pyrrole-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (249) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrrolo[3,2-c]pyridine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (250) (1-(5-(cyclopropylethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (251) (1-(5-(cyclopentylethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (252) (1-(5-(cyclohexylethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (253) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(morpholinomethyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (254) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((dimethylamino)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (255) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-((dimethylamino)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (256) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(phenylethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (257) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-fluorophenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (258) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-4-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (259) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-2-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (260) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-3-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (261) (3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(morpholino)methanone; (262) 4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)-N,N-dimethylbenzamide; (263) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(morpholino)methanone; (264) 6-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)-N,N-dimethylpicolinamide; (265) (6-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)pyridine-2-yl)(morpholino)methanone; (266) 2-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)cyclobutyl)propan-2-ol; (267) (1-(2-((2-(1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (268) (4-methyl-1-(2-((2-(1-(methylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)methanol; (269) (1-(2-((2-(6-fluoropyridine-3-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (270) (4-methyl-1-(5-((1-methyl-1H-pyrazole-4-yl)ethynyl)-2-((2-((2-(methylsulfonyl)phenyl)amino)pyrimidine-4-yl)amino)pyridine-4-yl)piperidine-4-yl)methanol; (271) (1-(5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)-2-((2-((2-(methylsulfonyl)phenyl)amino)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (272) 4-(4-((4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)amino)pyrimidine-2-yl)-N,N,3-trimethyl-1H-pyrazole-1-sulfonamide; (273) 4-(4-((4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)amino)pyrimidine-2-yl)-N,N-dimethyl-1H-pyrazole-1-sulfonamide; (274) 4-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)buto-3-in-1-ol; (275) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(4,4,4-trifluorobuto-1-in-1-yl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (276) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(4-fluorobuto-1-in-1-yl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (277) (1-(5-(buto-3-en-1-in-1-yl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (278) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-((dimethylamino)methyl)pyridine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (279) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((6-((4-methylpiperazine-1-yl)methyl)pyridine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (280) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(pyridine-3-ylethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol; (281) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-methoxy-4-methylpiperidine-1-yl)-5-(pyridine-3-ylethynyl)pyridine-2-yl)pyrimidine-4-amine; (282) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-(pyridine-3-ylethynyl)-4-(1-oxa-8-azaspiro[4.5]decane-8-yl)pyridine-2-yl)pyrimidine-4-amine; (283) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-(pyridine-3-ylethynyl)-4-(1-oxa-7-azaspiro[3.5]nonane-7-yl)pyridine-2-yl)pyrimidine-4-amine; (284) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)-2-methylpent-4-in-2-ol; (285) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(4-morpholinbut-1-in-1-yl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (286) 3-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)prop-2-in-1-yl)oxetan-3-ol; (287) 5-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)pento-4-in-2-ol; (288) N-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)prop-2-in-1-yl)-2,2,2-trifluoroacetamide; (289) 4-(3-(6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)prop-2-in-1-yl)thiomorpholine 1,1-dioxide; (290) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-(trifluoromethyl)-1H-pyrazole-5-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (291) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-(trifluoromethyl)thiazole-2-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (292) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-(trifluoromethyl)thiazole-5-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (293) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-fluoropiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine formate; (294) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine formate; (295) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((dimethylamino)methyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (296) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (297) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethinyl)-4-(2-methyl-2,8-diazaspiro[4.5]decane-8-yl)pyridine-2-yl)pyrimidine-4-amine formate; (298) N-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)piperidine-1-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (299) N-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (300) N-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-fluoropiperidine-1-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (301) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (302) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (303) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)pyridine-2-yl)pyrimidine-4-amine; (304) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-(hydroxymethyl)cyclohexane-1-ol; (305) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (306) (1R,3S)-3-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)methyl)cyclopentan-1-ol; (307) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol; (308) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (309) 5-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)ethynyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine; (310) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethinyl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine; (311) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine; (312) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine; (313) 5-((1-cyclopropyl-1H-pyrazole-4-yl)ethynyl)-N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)pyridine-2,4-diamine; (314) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -((1s,4s)-4-((dimethylamino)methyl)cyclohexyl)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine; (315) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-((dimethylamino)methyl)piperidine-4-ol; (316) 1-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-((dimethylamino)methyl)piperidine-4-ol; (317) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-((dimethylamino)methyl)piperidine-4-ol; (318) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methyl-1H-pyrazole-4-yl)ethinyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecane-3-yl)pyridine-2-yl)pyrimidine-4-amine; (319) N-(5-((1-cyclopropyl-1H-pyrazole-4-yl)ethinyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecane-3-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (320) N-(5-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)ethinyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecane-3-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (321) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(difluoromethyl)-1H-pyrazole-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecane-3-yl)pyridine-2-yl)pyrimidine-4-amine; (322) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)-4-(9-methyl-3,9-diazaspiro[5.5]undecane-3-yl)pyridine-2-yl)pyrimidine-4-amine; (323) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol; (324) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (325) 2-((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclohexyl)propan-2-ol; (326) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol; (327) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2-difluorocyclopropyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (328) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-ol; (329) 2-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)propan-2-ol; (330) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-4-yl)cyclopropane-1-ol; (331) ((1R,5S,6r)-3-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-3-azabicyclo[3.1.0]hexane-6-yl)methanol; (332) ((1R,3s,5S)-8-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-8-azabicyclo[3.2.1]octan-3-yl)methanol; (333) ((1S,5S)-3-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-3-azabicyclo[3.1.0]hexane-1-yl)methanol; (334) 1-(1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-4-yl)ethane-1-one; (335) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (336) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (337) 2-((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)amino)cyclohexyl)propan-2-ol; (338) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol; (339) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (340) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (341) (1S,3S)-3-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (342) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-fluoropiperidine-4-yl)methanol; (343) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)piperidine-3-ol; (344) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)-1-methylcyclohexane-1-ol; (345) N 2 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)-N 4 -((1s,4s)-4-((2-fluoroethyl)amino)cyclohexyl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2,4-diamine; (346) 2-((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)propan-2-ol; (347) 7-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-2-methyl-7-azaspiro[3.5]nonan-2-ol; (348) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (349) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (350) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-methyloxetane-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (351) 1-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)cyclobutan-1-ol; (352) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(oxetane-3-ylethinyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (353) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(oxetan-3-ylethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (354) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)oxetan-3-ol; (355) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)tetrahydrofuran-3-ol; (356) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridine-3-yl)ethynyl)tetrahydrofuran-3-ol; (357) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)tetrahydro-2H-pyran-3-ol; (358) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (359) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (360) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (361) (1r,4r)-4-(((2-((2-((1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol; (362) (5s,8s)-8-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)-1-azaspiro[4.5]decane-2-one; (363) (1r,4r)-4-(((2-((2-((1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)amino)methyl)-1-methylcyclohexane-1-ol; (364) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidine-2-yl)ethinyl)pyridine-4-yl)-4-methylpiperidine-4-ol; (365) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((5-(morpholinomethyl)pyrimidine-2-yl)ethinyl)pyridine-4-yl)-4-methoxypiperidine-4-ol; (366) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((5-(morpholinomethyl)pyrimidine-2-yl)ethynyl)-4-(1-oxa-8-azaspiro[4.5]decane-8-yl)pyridine-2-yl)pyrimidine-4-amine; (367) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((5-(morpholinomethyl)pyrimidine-2-yl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonanane-7-yl)pyridin-2-yl)pyrimidine-4-amine; (368) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol; (369) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)pyridine-4-yl)-4-methoxypiperidine-4-ol; (370) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((4-((4-methylpiperazine-1-yl)methyl)phenyl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonanane-7-yl)pyridine-2-yl)pyrimidine-4-amine; (371) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylpyrrolidine-3-yl)ethynyl)pyridine-4-yl)-4-methoxypiperidine-4-ol; (372) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methylpyrrolidine-3-yl)ethynyl)-4-(1-oxa-8-azaspiro[4.5]decane-8-yl)pyridine-2-yl)pyrimidine-4-amine; (373) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(5-((1-methylpyrrolidine-3-yl)ethynyl)-4-(1-oxa-7-azaspiro[3.5]nonanane-7-yl)pyridine-2-yl)pyrimidine-4-amine; (374) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (375) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol; (376) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (377) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)amino)methyl)-1-methylcyclohexane-1-ol; (378) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((tetrahydrofuran-2-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (379) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (380) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)methyl)-1-methylcyclohexane-1-ol; (381) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexyl)methanol; (382) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoro-4-((methylamino)methyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (383) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-fluoro-4-(((2-fluoroethyl)amino)methyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (384) (S)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-((dimethylamino)methyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (385) (S)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-((dimethylamino)methyl)piperidine-1-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (386) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (387) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (388) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexyl)methanol; (389) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (390) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (391) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (392) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)piperidine-4-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexyl)methanol; (393) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (394) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (395) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(cyclopropylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (396) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(3-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-methyl-1H-pyrazole-4-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (397) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (398) (1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol; (399) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (400) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexyl)methanol; (401) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(methylsulfonyl)pyrrolidine-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (402) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (403) (1r,4r)-4-(((2-((2-((1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol; (404) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol; (405) ((1r,4r)-4-(((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-methylcyclopropyl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexyl)methanol; (406) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)-5-((1-methylcyclopropyl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (407) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-((1-methylcyclopropyl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (408) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one; (409) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-((((1r,4r)-4-hydroxycyclohexyl)methyl)amino)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one; (410) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-hydroxy-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one; (411) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-((((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)amino)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one; (412) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one; (413) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one; (414) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-hydroxycyclohexyl)amino)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one; (415) 1-(3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)pyrrolidine-1-yl)-2,2,2-trifluoroethane-1-one; (416) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (417) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol; (418) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-((dimethylamino)methyl)-4-methylpiperidine-1-yl)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (419) 2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)-N-(4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine-2-yl)pyrimidine-4-amine; (420) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (421) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-(((2R)-2-(trifluoromethyl)tetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (422) ((1s,4s)-4-((5-((7-Oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)cyclohexyl)methanol; (423) (1r,4r)-4-(((5-((7-Oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)methyl)cyclohexane-1-ol; (424) 1-(5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethinyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)-4-methylpiperidine-4-ol; (425) ((1r,4r)-4-(((5-((7-Oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)methyl)cyclohexyl)methanol; (426) N-(5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-4-(4-(2-(dimethylamino)ethyl)piperidine-1-yl)pyridine-2-yl)-2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-amine; (427) (1s,4s)-4-((5-((7-oxabicyclo[2.2.1]heptan-2-yl)ethynyl)-2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)pyridine-4-yl)amino)cyclohexane-1-ol; (428) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridine-3-yl)ethinyl)tetrahydrothiophene 1,1-dioxide; (429) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-hydroxy-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)tetrahydrothiophene 1,1-dioxide; (430) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (431) (1r,4r)-4-(((2-((2-((1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)methyl)cyclohexane-1-ol; (432) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol; (433) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (434) ((1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexyl)methanol; (435) 1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-ol; (436) (1s,4s)-4-((2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((3-fluorotetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)amino)cyclohexane-1-ol; (437) 3-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethinyl)tetrahydrothiophene 1,1-dioxide; (438) (1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((2-methyltetrahydrofuran-3-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol; (439) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol; (440) (R)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)piperidine-3-ol; (441) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(((1s,4s)-4-(hydroxymethyl)cyclohexyl)amino)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone; (442) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-hydroxy-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone; (443) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-((((1r,4r)-4-(hydroxymethyl)cyclohexyl)methyl)amino)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone; (444) (R)-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(3-hydroxypiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone; (445) (S)-(4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(3-hydroxypiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone; (446) (4-((6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-4-(4-(hydroxymethyl)-4-methylpiperidine-1-yl)pyridine-3-yl)ethynyl)phenyl)(4-hydroxypiperidine-1-yl)methanone; (447) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-3-methylpiperidine-3-ol; (448) (S)-1-(2-((2-(1-(cyclopropylsulfonyl)-1H-pyrazole-4-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethinyl)pyridine-4-yl)-3-methylpiperidine-3-ol; and (449) (1-(2-((2-(4-(cyclopropylsulfonyl)piperazine-1-yl)pyrimidine-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazole-4-yl)ethynyl)pyridine-4-yl)-4-methylpiperidine-4-yl)methanol A compound according to claim 1, selected from the group consisting of the following, or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition for treating protein kinase-mediated diseases, comprising a compound according to any one of claims 1 to 14 or a pharmaceutically acceptable salt thereof as an active ingredient.

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, stomach cancer, lymphoma, pancreatic cancer, head and neck cancer, thyroid cancer, prostate cancer, skin cancer, or hematological malignancy.

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 compared to wild-type EGFR, comprising a compound according to any one of claims 1 to 14 or a pharmaceutically acceptable salt thereof as an active ingredient.

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