Pyrimidine / pyridine derivatives or salts thereof and pharmaceutical compositions comprising the same

Abstract

The present invention provides a novel pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof, a process for the preparation thereof, a pharmaceutical composition comprising the same and a use thereof. The pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof can be usefully applied for preventing or treating various blood cancers or solid tumors through excellent inhibitory activity against hematopoietic progenitor kinase 1 (HPK1).

Description

PYRIMIDINE / PYRIDINE DERIVATIVES OR SALTS THEREOF AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME

[0001] The present invention relates to a pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof having an excellent inhibitory activity against hematopoietic progenitor kinase 1 (HPK1), a process for the preparation thereof, a pharmaceutical composition comprising the same, and a use thereof.

[0002] Antibody-based cancer immunotherapy shows continuous anti-tumor effects in a significant proportion of cancer patients and thus the development of cancer immunotherapy will be one of the effective anti-cancer platforms in the future. Antibody-based cancer immunotherapy has been shown to improve survival rates compared to conventional standard therapies. However, the response rate thereof varies widely depending on tumor types, ranging from 15% in head and neck cancer patients to 87% in leukemia patients (Science 2018;23;359(6382):1350-1355). Such a limitation makes it difficult to utilize cancer immunotherapy as a broad-spectrum anticancer therapy and requires developing the biomarkers that can predict responsiveness (Nature 2017;18;541(7637):321-330; Nat. Rev. Cancer 2019; Mar;19(3):133-150). Therefore, in addition to the cancer immunotherapy, there is an urgent need for alternative approaches that modulate the response of immune cells.

[0003] Recently, there are being re-examined approaches for targeting the intracellular pathway that regulates immune function by small molecules. For increasing the efficacy of cancer immunotherapy based on said approaches, it is required to control immunosuppression in the tumor microenvironment and peripheral tolerance to tumor antigens. In addition, since most of cancer immunotherapies are based on the antibody and target the receptors present on the surface of cell membranes, it is difficult to develop antibody-based cancer immunotherapy that can act on the targets present within tumor cells or immune cells.

[0004] Hematopoietic progenitor kinase 1 (HPK1), a member of the MAP4K family, is a serine / threonine kinase and is mainly expressed only in the hematopoietic cell lineage (T cells, B cells, DC cells, mononuclear cells, NK cells, etc.). HPK1 involves in various signaling mechanisms such as JNK, AP-1, and NK-κB to regulate the function of immune cells (Genes Devel. 1996; 10:2251-2264, EMBO J. 1996; 15:7013-7025, Proc Nat Acad Sci USA. 2009; 106(34):14508-14513). For example, HPK1 plays a role in suppressing excessive activity of T cells through phosphorylation and activation of the T cell receptor adapter protein SLP-76 when the T cell receptor is activated by binding to a ligand (J. Exp. Med. 2007; 204:681). In addition, HPK1 inhibits the activity of B cells by interfering with signaling of the B cell receptor through phosphorylation of BLNK protein (J. Biol. Chem. 2012; 287:11037). Therefore, increase in proliferation of T cells and increase in inflammatory cytokines can be observed in HPK1 KO / KD mice in which the function of HPK1 is suppressed. And, decrease in tumor growth rate and increase in efficacy of cancer immunotherapy can be also observed in a tumor model using HPK1 KO / KD mice (Cell Rep. 2018; 25(1):80-94). In addition, it has been reported that the activity of COX-2 and PGE2 / adenosine is an important cause of reducing the efficacy of immunotherapy in the tumor microenvironment; and that tumor growth rate according to the immune response is decreased in HPK1 KD mice, even in the presence of high level of PGE2 (Cancer Immunol Immunother. 2010; 59(3):419-429). These mechanisms mean that, when HPK1 is inhibited in most of tumor patients, the activity of immune cells increases and the immunosuppression in the tumor microenvironment can also be improved. Therefore, the materials that inhibit HPK1 can be usefully applied to the prevention and treatment of any types of carcinomas, including various blood cancers and solid tumors.

[0005] The present inventors carried out various studies to develop a material having an excellent inhibitory activity against HPK1. As a result, the present inventors have found that a pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof has an excellent inhibitory activity against HPK1. Therefore, the pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof inhibits HPK1 to activate immune cells and improve the tumor microenvironment in which the immune system is suppressed, thereby being able to be usefully applied to the prevention and treatment of various blood cancers and solid tumors.

[0006] Therefore, the present invention provides said pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof, a process for the preparation thereof, a pharmaceutical composition comprising the same, and a use thereof.

[0007] According to an aspect of the present invention, there is provided a pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof.

[0008] According to another aspect of the present invention, there is provided a process for preparing said pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof.

[0009] According to still another aspect of the present invention, there is provided a pharmaceutical composition comprising said pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof as an active ingredient.

[0010] According to still another aspect of the present invention, there is provided a therapeutic method comprising administering said pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof.

[0011] According to still another aspect of the present invention, there is provided a use of said pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof for the manufacture of a medicament for inhibiting hematopoietic progenitor kinase 1.

[0012] It has been found by the present invention that the pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof has an excellent inhibitory activity against HPK1. Therefore, the compound or pharmaceutically acceptable salt thereof according to the present invention can be usefully applied for preventing or treating various blood cancers and solid tumors, through inhibiting the activity of HPK1.

[0013] As used herein, the term 'alkyl' refers to an aliphatic hydrocarbon radical, including a straight or branched aliphatic hydrocarbon radical. For example, the C1∼C6alkyl means aliphatic hydrocarbon having 1 to 6 carbon atoms, including methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, neopentyl, and isopentyl.

[0014] The term 'hydroxy' refers to the -OH group. The term 'alkoxy' refers to a radical formed by substituting the hydrogen atom in the hydroxyl group with an alkyl, unless otherwise defined. For example, the C1∼C6alkoxy includes methoxy, ethoxy, propoxy, n-butoxy, n-pentyloxy, isopropoxy, sec-butoxy, tert-butoxy, neopentyloxy, and isopentyloxy.

[0015] The term 'halogen' refers to the fluoro, bromo, chloro, or iodo group.

[0016] The term 'amino' refers to the -NH2group. The term 'alkylamino' refers to an amino group substituted with mono- or di-alkyl. For example, the C1∼C6alkylamino includes an amino group substituted with mono- or di- C1∼C6alkyl.

[0017] The term 'carbonyl' refers to -C(=O)-. The term 'aminocarbonyl' refers to a carbonyl group substituted with amino. The term 'alkylcarbonyl' refers to a carbonyl group substituted with alkyl. The term 'hydroxycarbonyl' refers to a carbonyl group substituted with hydroxy. The term 'alkoxycarbonyl' refers to a carbonyl group substituted with alkoxy. The term 'heterocycloalkylcarbonyl' refers to a carbonyl group substituted with heterocycloalkyl.

[0018] The term 'sulfonyl' refers to -SO2-. The term 'alkylsulfonyl' refers to a sulfonyl group substituted with alkyl.

[0019] The term 'cyano' refers to the -CN.

[0020] The term 'cycloalkyl' refers to a cyclic alkyl group, where the 'alkyl' is the same as defined in the above. For example, the cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc., but not limited thereto.

[0021] The term 'heterocycloalkyl' refers to a 3- to 12-membered cycloalkyl or spirocycloalkyl group having one to three heteroatoms selected from N, O and S. For example, the heterocycloalkyl includes azetidinyl, pyrrolidinyl, piperidinyl, N-methylpiperidinyl, pyrazolidinyl, morpholinyl, piperazinyl, tetrahydropyranyl, tetrahydrofuranyl, oxazolidin-2-onyl, 2,8-diazaspiro[4.5]decanyl, etc., but not limited thereto.

[0022] The term 'aryl' refers to a 3- to 12-membered aromatic ring and may be a single ring or multiple rings. For examples, the aryl includes phenyl, naphthyl, biphenyl, etc., but not limited thereto.

[0023] The term 'heteroaryl' refers to a 3- to 12-membered aromatic ring having one to three heteroatoms selected from N, O and S and may be a single ring or multiple rings. For example, the heteroaryl includes thienyl, furyl, pyrrolyl, pyrazolyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl, quinolinyl, quinazolinyl, quinoxalinyl, [1,2,4]triazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridin-6-yl, etc., but not limited thereto.

[0024] The term 'substituted' refers to being substituted at one or more substitutable positions. For example, the expression 'C1∼C6alkyl substituted with halogen' includes a C1∼C6alkyl group substituted with one or more halogens, for example, 1, 2 or 3 halogens.

[0025] The present invention provides a pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof having an excellent inhibitory activity against HPK1, i.e., the following compound of Formula 1 or pharmaceutically acceptable salt thereof:

[0026] <Formula 1>

[0027]

[0028] wherein,

[0029] P1and P2are, independently each other, -CH= or -N=,

[0030] R1and R2are, independently each other, a C1∼C6alkyl group; a C3∼C6cycloalkyl group optionally substituted with hydroxy or amino; or a heterocycloalkyl optionally substituted with hydroxy or amino, or

[0031] R1and R2form a heterocycloalkyl together with the nitrogen atom to which they are bonded, wherein the heterocycloalkyl is optionally substituted with one or two groups selected from the group consisting of halogen, amino, hydroxy, C1∼C6alkyl, C1∼C6alkoxy, C1∼C6alkyl substituted with halogen, C1∼C6alkyl substituted with hydroxy, C3∼C6cycloalkyl, C3∼C6cycloalkyl substituted with hydroxy, mono- or di-C1∼C6alkylamino, aminocarbonyl, C1∼C6alkylcarbonylamino, and mono- or di-C1∼C6alkylamino-C1∼C6alkyl,

[0032] X is -C(R3)= or -N=,

[0033] R3is hydrogen, halogen, cyano, nitro, amino, C1∼C3alkyl, C1∼C3alkyl substituted with halogen, hydroxycarbonyl, C1∼C3alkoxycarbonyl, aminocarbonyl, mono- or di-C1∼C3alkylaminocarbonyl, or C1∼C3alkylsulfonyl,

[0034] A is a 5- to 12-membered aryl group; a 5- to 12-membered heteroaryl group having one to three heteroatoms selected from N, O and S; or a 5- to 12-membered heterocycloalkyl group having one to three heteroatoms selected from N, O and S, wherein the aryl group, the heteroaryl group, or the heterocycloalkyl group is optionally substituted with one to three groups selected from the group consisting of halogen, amino, hydroxy, C1∼C6alkyl, C1∼C6alkyl substituted with hydroxy, C1∼C6alkoxy, C3∼C6cycloalkyl, aldehyde, mono- or di-C1∼C3alkylamino, mono- or di-C1∼C3alkylamino-C1∼C6alkyl, C1∼C6alkoxycarbonyl, mono- or di-C1∼C6alkylaminocarbonyl, C1∼C6alkylaminocarbonyl substituted with halogen, C3∼C6cycloalkylaminocarbonyl, C3∼C6cycloalkylaminocarbonyl substituted with halogen, C3∼C6cycloalkylaminocarbonyl substituted with hydroxy, heterocycloalkyl-C1∼C3alkyl optionally substituted with hydroxy, heterocycloalkylcarbonyl optionally substituted with halogen, and oxo,

[0035] L is a bond, -C(O)-, -(CH2)n-, -C(O)NH-, or -C≡C-,

[0036] n is 1, 2, or 3,

[0037] Q is a bond; C3∼C6cycloalkyl; a 3- to 12-membered heterocycloalkyl having one to three heteroatoms selected from N, O and S; a 5- to 12-membered heteroaryl having one to three heteroatoms selected from N, O and S; or a 5- to 12-membered aryl,

[0038] m is 1, 2, or 3,

[0039] Y is, independently each other, hydrogen, hydroxy, halogen, amino, C1∼C6alkyl, C1∼C6alkyl substituted with hydroxy, C1∼C6alkyl substituted with halogen, C1∼C6alkyl substituted with mono- or di-C1∼C3alkylamino, C1∼C6alkoxy, C1∼C6alkoxy substituted with C1∼C3alkoxy, C1∼C6alkoxy substituted with halogen, C1∼C6alkoxy substituted with mono- or di-C1∼C3alkylamino, C1∼C6alkoxy-C1∼C6alkyl, C3∼C6cycloalkyl, C3∼C6cycloalkyl-C1∼C3alkyl, C3∼C6cycloalkyl-C1∼C3alkyl substituted with halogen, C1∼C3alkylcarbonyl, C3∼C6cycloalkyl-aminocarbonyl substituted with hydroxy, mono- or di-C1∼C3alkylamino, C1∼C6alkylamino substituted with mono- or di-C1∼C3alkylamino, aminocarbonyl-C1∼C6alkyl, C1∼C3alkoxycarbonyl-C1∼C6alkyl, C1∼C3alkylcarbonylamino, mono- or di-C1∼C6alkylaminocarbonyl, mono- or di-C1∼C6alkylaminocarbonylamino, or mono- or di-C1∼C6alkylaminocarbonyl-C1∼C6alkyl, or

[0040] a heterocycloalkyl-containing group selected from the group consisting of azetidinyl; azetidinyl-C1∼C6alkyl; tetrahydropyranyl; tetrahydrofuranyl; pyrrolidinyl; pyrrolidinyl-C1∼C3alkyl; piperidinyl; piperidinyl-C1∼C3alkyl; piperidinylcarbonyl; piperidinyloxy; piperazinyl; piperazinyl-C1∼C3alkyl; piperazinylcarbonyl; oxetanyl; morpholinyl; morpholinyl-C1∼C3alkyl; and morpholinylcarbonyl, wherein the heterocycloalkyl of the heterocycloalkyl-containing group is optionally substituted with one to four groups selected from the group consisting of halogen, hydroxy, amino, oxo, C1∼C3alkyl, C1∼C3alkyl substituted with hydroxy, and mono- or di-C1∼C3alkylamino.

[0041] In an embodiment of the present invention, P1may be -CH= and P2may be -CH= or -N=. In another embodiment of the present invention, P1may be -N= and P2may be -CH=.

[0042] In the compound of Formula 1 or pharmaceutically acceptable salt thereof according to the present invention, R1and R2may form piperidine, azetidine, pyrrolidine, piperazine, or 2,8-diazaspiro[4.5]decane together with the nitrogen atom to which they are bonded. In an embodiment, R1may be a C1∼C6alkyl group and R2may be a C3∼C6cycloalkyl group substituted with hydroxy.

[0043] In an embodiment of the present invention, X may be -N=.

[0044] In another embodiment of the present invention, X may be -C(R3)= and R3may be H, -F, -Cl, -CH3, -CN, -NO2, -NH2, -C(O)OH, -C(O)OCH3, -C(O)NH2, -C(O)N(CH3)2, or -SO2CH3.

[0045] In the compound of Formula 1 or pharmaceutically acceptable salt thereof according to the present invention, A may be preferably phenyl, pyridinyl, thienyl, [1,2,4]triazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, quinolinyl, quinoxalinyl, or oxazolidinyl. In an embodiment, A may be optionally substituted with one to three groups selected from the group consisting of halogen, amino, hydroxy, C1∼C6alkyl, C1∼C6alkyl substituted with hydroxy, C1∼C6alkoxy, aldehyde, mono- or di-C1∼C3alkylamino-C1∼C6alkyl, C1∼C6alkoxycarbonyl, mono- or di-C1∼C6alkylaminocarbonyl, azetidinyl-C1∼C3alkyl substituted with hydroxy, azetidinylcarbonyl optionally substituted with one or two halogens, pyrrolidinylcarbonyl optionally substituted with one or two halogens, and oxo,

[0046] In the compound of Formula 1 or pharmaceutically acceptable salt thereof according to the present invention, A may be particularly preferably phenyl. That is, particularly preferably, the present invention includes a compound of Formula 1a or pharmaceutically acceptable salt thereof:

[0047] <Formula 1a>

[0048]

[0049] wherein,

[0050] R1and R2form a heterocycloalkyl together with the nitrogen atom to which they are bonded, wherein the heterocycloalkyl is optionally substituted with one or two groups selected from the group consisting of halogen, amino, hydroxy, C1∼C6alkyl, C1∼C6alkoxy, C1∼C6alkyl substituted with halogen, C1∼C6alkyl substituted with hydroxy, C3∼C6cycloalkyl, C3∼C6cycloalkyl substituted with hydroxy, mono- or di-C1∼C6alkylamino, aminocarbonyl, C1∼C6alkylcarbonylamino, and mono- or di-C1∼C6alkylamino-C1∼C6alkyl,

[0051] X is -C(R3)= or -N=,

[0052] R3is hydrogen, halogen, cyano, nitro, amino, C1∼C3alkyl, C1∼C3alkyl substituted with halogen, hydroxycarbonyl, C1∼C3alkoxycarbonyl, aminocarbonyl, mono- or di-C1∼C3alkylaminocarbonyl, or C1∼C3alkylsulfonyl,

[0053] R4is, independently each other, halogen, amino, hydroxy, C1∼C6alkyl, C1∼C6alkyl substituted with hydroxy, C1∼C6alkoxy, C3∼C6cycloalkyl, aldehyde, mono- or di-C1∼C3alkylamino, mono- or di-C1∼C3alkylamino-C1∼C6alkyl, C1∼C6alkoxycarbonyl, mono- or di-C1∼C6alkylaminocarbonyl, C1∼C6alkylaminocarbonyl substituted with halogen, C3∼C6cycloalkylaminocarbonyl, C3∼C6cycloalkylaminocarbonyl substituted with halogen, C3∼C6cycloalkylaminocarbonyl substituted with hydroxy, heterocycloalkyl-C1∼C3alkyl optionally substituted with hydroxy, or heterocycloalkylcarbonyl optionally substituted with halogen,

[0054] o is 0, 1, 2, or 3,

[0055] L is a bond, -C(O)-, -(CH2)n-, -C(O)NH-, or -C≡C-,

[0056] n is 1, 2, or 3,

[0057] Q is a bond; C3∼C6cycloalkyl; a 3- to 12-membered heterocycloalkyl having one to three heteroatoms selected from N, O and S; a 5- to 12-membered heteroaryl having one to three heteroatoms selected from N, O and S; or a 5- to 12-membered aryl,

[0058] m is 1, 2, or 3,

[0059] Y is, independently each other, hydrogen, hydroxy, halogen, amino, C1∼C6alkyl, C1∼C6alkyl substituted with hydroxy, C1∼C6alkyl substituted with halogen, C1∼C6alkyl substituted with mono- or di-C1∼C3alkylamino, C1∼C6alkoxy, C1∼C6alkoxy substituted with C1∼C3alkoxy, C1∼C6alkoxy substituted with halogen, C1∼C6alkoxy substituted with mono- or di-C1∼C3alkylamino, C1∼C6alkoxy-C1∼C6alkyl, C3∼C6cycloalkyl, C3∼C6cycloalkyl-C1∼C3alkyl, C3∼C6cycloalkyl-C1∼C3alkyl substituted with halogen, C1∼C3alkylcarbonyl, C3∼C6cycloalkyl-aminocarbonyl substituted with hydroxy, mono- or di-C1∼C3alkylamino, C1∼C6alkylamino substituted with mono- or di-C1∼C3alkylamino, aminocarbonyl-C1∼C6alkyl, C1∼C3alkoxycarbonyl-C1∼C6alkyl, C1∼C3alkylcarbonylamino, mono- or di-C1∼C6alkylaminocarbonyl, mono- or di-C1∼C6alkylaminocarbonylamino, or mono- or di-C1∼C6alkylaminocarbonyl-C1∼C6alkyl, or

[0060] a heterocycloalkyl-containing group selected from the group consisting of azetidinyl; azetidinyl-C1∼C6alkyl; tetrahydropyranyl; tetrahydrofuranyl; pyrrolidinyl; pyrrolidinyl-C1∼C3alkyl; piperidinyl; piperidinyl-C1∼C3alkyl; piperidinylcarbonyl; piperidinyloxy; piperazinyl; piperazinyl-C1∼C3alkyl; piperazinylcarbonyl; oxetanyl; morpholinyl; morpholinyl-C1∼C3alkyl; and morpholinylcarbonyl, wherein the heterocycloalkyl of the heterocycloalkyl-containing group is optionally substituted with one to four groups selected from the group consisting of halogen, hydroxy, amino, oxo, C1∼C3alkyl, C1∼C3alkyl substituted with hydroxy, and mono- or di-C1∼C3alkylamino.

[0061] In the compound of Formula 1a or pharmaceutically acceptable salt thereof, R1and R2may form preferably piperidine, azetidine, pyrrolidine, piperazine, or 2,8-diazaspiro[4.5]decane together with the nitrogen atom to which they are bonded.

[0062] In the compound of Formula 1a or pharmaceutically acceptable salt thereof, X may be preferably -N=.

[0063] In the compound of Formula 1a or pharmaceutically acceptable salt thereof, X may be -C(R3)= and R3may be preferably H, -F, -Cl, -CH3, -CN, -NO2, -NH2, -C(O)OH, -C(O)OCH3, -C(O)NH2, -C(O)N(CH3)2, or -SO2CH3.

[0064] In the compound of Formula 1a or pharmaceutically acceptable salt thereof, R4may be, independently each other, preferably halogen, amino, hydroxy, C1∼C6alkyl, C1∼C6alkyl substituted with hydroxy, C1∼C6alkoxy, aldehyde, mono- or di-C1∼C3alkylamino-C1∼C6alkyl, C1∼C6alkoxycarbonyl, mono- or di-C1∼C6alkylaminocarbonyl, azetidinyl-C1∼C3alkyl substituted with hydroxy, azetidinylcarbonyl optionally substituted with one or two halogens, or pyrrolidinylcarbonyl optionally substituted with one or two halogens.

[0065] In the compound of Formula 1 (preferably Formula 1a) or pharmaceutically acceptable salt thereof of the present invention, when Q is a ring such as C3∼C6cycloalkyl; a 3- to 12-membered heterocycloalkyl having one to three heteroatoms selected from N, O and S; a 5- to 12-membered heteroaryl having one to three heteroatoms selected from N, O and S; or a 5- to 12-membered aryl, Y may be substituted at any substitutable position(s) within the ring.

[0066] In the compound of Formula 1 (preferably Formula 1a) or pharmaceutically acceptable salt thereof of the present invention, Q may be a bond, C3∼C6cycloalkyl, tetrahydropyranyl, pyrrolidinyl, phenyl, pyridinyl, pyrazolyl, thiazolyl, imidazo[1,2-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridin-6-yl,2H-benzo[b][1,4]oxazin-3(4H)-onyl, 3,4-dihydroquinolin-2(1H)-onyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, 2H-pyrido[3,2-b]-1,4-oxazin-3(4H)-onyl, 1,4-dihydro-2H-benzo[d][1,3]oxazin-2-onyl, or 3,4-dihydro-1,8-naphthyridin-2(1H)-onyl.

[0067] In the compound of Formula 1 (preferably Formula 1a) or pharmaceutically acceptable salt thereof of the present invention, Y may be, independently each other, hydrogen, hydroxy, halogen, amino, C1∼C6alkyl, C1∼C6alkyl substituted with hydroxy, C1∼C6alkyl substituted with halogen, C1∼C6alkyl substituted with mono- or di-C1∼C3alkylamino, C1∼C6alkoxy, C1∼C6alkoxy substituted with C1∼C3alkoxy, C1∼C6alkoxy substituted with halogen, C1∼C6alkoxy substituted with mono- or di-C1∼C3alkylamino, C1∼C6alkoxy-C1∼C6alkyl, C3∼C6cycloalkyl, C3∼C6cycloalkyl-C1∼C3alkyl, C3∼C6cycloalkyl-C1∼C3alkyl substituted with halogen, C1∼C3alkylcarbonyl, C3∼C6cycloalkyl-aminocarbonyl substituted with hydroxy, mono- or di-C1∼C3alkylamino, C1∼C6alkylamino substituted with mono- or di-C1∼C3alkylamino, aminocarbonyl-C1∼C6alkyl, C1∼C3alkoxycarbonyl-C1∼C6alkyl, C1∼C3alkylcarbonylamino, mono- or di-C1∼C6alkylaminocarbonyl, mono- or di-C1∼C6alkylaminocarbonylamino, or mono- or di-C1∼C6alkylaminocarbonyl-C1∼C6alkyl.

[0068] In the compound of Formula 1 (preferably Formula 1a) or pharmaceutically acceptable salt thereof of the present invention, one of Y may be a heterocycloalkyl-containing group selected from the group consisting of azetidinyl; azetidinylmethyl; tetrahydropyranyl; tetrahydrofuranyl; pyrrolidinyl; pyrrolidinylmethyl; pyrrolidinylethyl; piperidinyl; piperidinylmethyl; piperidinylcarbonyl; piperidinyloxy; piperazinyl; piperazinylmethyl; piperazinylcarbonyl; oxetanyl; morpholinyl; morpholinylmethyl; morpholinylethyl; and morpholinylcarbonyl, and the remaining Y may be hydrogen. In addition, the heterocycloalkyl of the heterocycloalkyl-containing group may be substituted with one to four groups selected from the group consisting of halogen, hydroxy, amino, oxo, C1∼C3alkyl, C1∼C3alkyl substituted with hydroxy, and mono- or di-C1∼C3alkylamino.

[0069] In the compound of Formula 1 or pharmaceutically acceptable salt, preferable compounds include the following compound or pharmaceutically acceptable salt thereof selected from the group consisting of:

[0070] (S)-cyclopropyl(4-(3-hydroxypiperidin-1-yl)-6-((2-(5-methylpyridin-3-yl)pyrimidin-4-yl)amino)pyridin-3-yl)methanone;

[0071] (S)-(6-((2-(5-aminopyridin-3-yl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)(cyclopropyl)methanone;

[0072] (S)-cyclopropyl(4-(3-hydroxypiperidin-1-yl)-6-((2-(5-methoxypyridin-3-yl)pyrimidin-4-yl)amino)pyridin-3-yl)methanone;

[0073] (S)-cyclopropyl(6-((2-(3-hydroxyphenyl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)methanone;

[0074] (S)-cyclopropyl(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)methanone;

[0075] cyclopropyl(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4-(3-hydroxyazetidin-1-yl)pyridin-3-yl)methanone;

[0076] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0077] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0078] (R)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0079] 1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)azetidin-3-ol;

[0080] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0081] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0082] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0083] (3S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0084] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0085] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0086] (S)-1-(5-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0087] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(4-(tetrahydro-2H-pyran-4-yl)phenyl)pyridin-4-yl)piperidin-3-ol;

[0088] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(4-(4-methylpiperazin-1-yl)phenyl)pyridin-4-yl)piperidin-3-ol;

[0089] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-morpholino-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0090] (S)-1-(2-((2-(4-(hydroxymethyl)thiophen-2-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0091] (S)-1-(2-((2-(2,6-difluorophenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0092] (S)-1-(2-((2-(3,6-difluoro-2-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0093] (S)-1-(2-((2-(2,3-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0094] (S)-1-(2-((2-(2-ethoxy-6-fluorophenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0095] (S)-1-(2-((2-([1,2,4]triazolo[1,5-a]pyridin-7-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0096] (S)-1-(2-((2-(pyrazolo[1,5-a]pyridin-3-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0097] (S)-1-(2-((2-(quinoxalin-6-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0098] (S)-1-(2-((2-(8-fluoroquinolin-7-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0099] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-((4-methylpiperazin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0100] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0101] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-(morpholinomethyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0102] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-((4-hydroxypiperidin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0103] 1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-carboxamide;

[0104] (S)-1-(2-((6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0105] (S)-(6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(4-methylpiperazin-1-yl)methanone;

[0106] (S)-(6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(morpholino)methanone;

[0107] (S)-(6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(4-hydroxypiperidin-1-yl)methanone;

[0108] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-(((S)-3-fluoropyrrolidin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0109] (3S)-1-(2-((5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0110] (3S)-1-(2-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0111] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0112] (3S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-((3-hydroxypyrrolidin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0113] N-(4-(3-(dimethylamino)pyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0114] (1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-3-methylpyrrolidin-3-yl)methanol;

[0115] N-(4-(4-((dimethylamino)methyl)-4-fluoropiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0116] (4-(2,2-difluoroethyl)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)methanol;

[0117] (3S)-1-(6'-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0118] 1-((6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4'-((S)-3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)methyl)piperidin-3-ol;

[0119] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-carboxamide;

[0120] (R)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-carboxamide;

[0121] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0122] (R)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0123] (6'-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4'-((S)-3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(4-hydroxypiperidin-1-yl)methanone;

[0124] (S)-1-(6'-((4-aminopiperidin-1-yl)methyl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0125] (S)-1-(6'-ethoxy-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0126] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-(trifluoromethyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0127] (3S)-1-(2-((6-(2-fluoro-6-methoxyphenyl)-5-methylpyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0128] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinonitrile;

[0129] methyl 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinate;

[0130] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(imidazo[1,2-a]pyridin-6-yl)pyridin-4-yl)piperidin-3-ol;

[0131] (S)-1-(5-([1,2,4]triazolo[4,3-a]pyridin-6-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0132] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)nicotinonitrile;

[0133] N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0134] 1-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)cyclopropan-1-ol;

[0135] 1-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0136] 2-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol;

[0137] 2-(2-fluoro-6-methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;

[0138] (S)-1-(2-((2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0139] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine;

[0140] methyl 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinate;

[0141] (S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0142] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0143] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0144] (3S)-1-(2-((5-chloro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0145] 4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)pyridin-2-amine;

[0146] (R)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0147] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0148] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0149] (S)-3-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)pyridin-2-ol;

[0150] (S)-1-(6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-methylpiperidin-4-yl)oxy)-[2,3'-bipyridin]-4'-yl)piperidin-3-ol;

[0151] (S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-6-amine;

[0152] (S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(1-methylpiperidin-4-yl)-[3,3'-bipyridin]-6-amine;

[0153] 2-(2-fluoro-6-methoxyphenyl)-N-(5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-4-(3-(2,2,2-trifluoroethyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0154] 2-(2-fluoro-6-methoxyphenyl)-N-(4-(3-(fluoromethyl)piperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;

[0155] N-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)acetamide;

[0156] 2-(2-fluoro-6-methoxyphenyl)-N-(5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-4-(4-(trifluoromethyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

[0157] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-amine;

[0158] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-amine;

[0159] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-amine;

[0160] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0161] N-(4-(2,8-diazaspiro[4.5]decan-8-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0162] N-(4-(2,8-diazaspiro[4.5]decan-2-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0163] (3R,4R)-4-fluoro-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0164] (3R,4R)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-(hydroxymethyl)piperidin-3-ol;

[0165] (R)-N-(4-(3-aminopyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0166] (S)-N-(4-(3-aminopyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0167] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(2-(1-methylpiperidin-4-yl)thiazol-5-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0168] (S)-4-(3-aminopiperidin-1-yl)-N-(2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-yl)-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-6-amine;

[0169] 4-((S)-3-aminopiperidin-1-yl)-N-(5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-amine;

[0170] (S)-(4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)methanol;

[0171] (S)-(4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)methanol;

[0172] (S)-(4-(4-((4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)methanol;

[0173] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(4-((dimethylamino)methyl)-2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0174] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(4-((dimethylamino)methyl)-2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0175] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(4-((dimethylamino)methyl)-2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0176] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0177] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0178] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0179] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0180] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0181] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinamide;

[0182] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-N,N-dimethylnicotinamide;

[0183] 4-((S)-3-aminopiperidin-1-yl)-N-(5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-amine;

[0184] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-amine;

[0185] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0186] 2-(2-fluoro-6-methoxyphenyl)-N-(4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;

[0187] (S)-4-(3-aminopiperidin-1-yl)-N6-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-N6',N6'-dimethyl-[3,3'-bipyridin]-6,6'-diamine;

[0188] (S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(pyrrolidin-1-yl)-[3,3'-bipyridin]-6-amine;

[0189] (S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(piperidin-1-yl)-[3,3'-bipyridin]-6-amine;

[0190] (S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-morpholino-[3,3'-bipyridin]-6-amine;

[0191] (S)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-(methylamino)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0192] (R)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-(methylamino)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0193] (S)-2-(2-fluoro-6-methoxyphenyl)-N-(4-(3-(methylamino)pyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;

[0194] (S)-N-(4-(3-(ethylamino)pyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0195] (R)-N-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)pyrrolidin-3-yl)acetamide;

[0196] (S)-3-(6-((4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyridin-2-yl)oxazolidin-2-one;

[0197] (S)-N-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)pyrrolidin-3-yl)acetamide;

[0198] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinamide;

[0199] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)-N,N-dimethylnicotinamide;

[0200] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0201] (S)-2-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide;

[0202] (S)-2-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)ethan-1-ol;

[0203] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0204] N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0205] 2-(2-fluoro-6-methoxyphenyl)-N-(4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;

[0206] N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)-6'-morpholino-[3,3'-bipyridin]-6-amine;

[0207] (S)-3-(6-((4-(3-aminopiperidin-1-yl)-6'-morpholino-[3,3'-bipyridin]-6-yl)amino)pyridin-2-yl)oxazolidin-2-one;

[0208] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)amino)nicotinic acid;

[0209] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)amino)nicotinamide;

[0210] 6-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)-N,N-dimethylnicotinamide;

[0211] 6-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinamide;

[0212] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinamide;

[0213] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinamide;

[0214] (3S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0215] 4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)pyridin-2-amine;

[0216] N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0217] N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0218] 4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-morpholino-[3,3'-bipyridin]-6-amine;

[0219] (3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0220] N²-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0221] 4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)pyridin-2-amine;

[0222] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-amine;

[0223] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-amine;

[0224] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-amine;

[0225] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-amine;

[0226] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0227] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0228] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0229] 6-((5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinamide;

[0230] (S)-1-(2-((2-(2-fluoro-4-(hydroxymethyl)-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0231] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0232] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0233] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0234] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0235] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0236] (S)-3-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)propanamide;

[0237] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(azetidin-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0238] N²-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0239] N²-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0240] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0241] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0242] N2-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0243] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0244] (S)-5-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridazin-3-amine;

[0245] (S)-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)(4-methylpiperazin-1-yl)methanone;

[0246] (3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0247] (3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0248] (3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0249] (3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0250] N²-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0251] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0252] (3S)-1-(2-((6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0253] (3S)-1-(2-((5-amino-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0254] methyl (S)-4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxybenzoate;

[0255] (S)-4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxy-N-methylbenzamide;

[0256] (S)-4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxy-N,N-dimethylbenzamide;

[0257] (S)-1-(2-((2-(4-((3-hydroxyazetidin-1-yl)methyl)thiophen-2-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0258] (S)-3-fluoro-4-(4-((4-(3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-5-methoxybenzaldehyde;

[0259] (S)-1-(2-((2-(2-fluoro-6-methoxy-4-((methylamino)methyl)phenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0260] 6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0261] 6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)-N-((R)-1-methylpyrrolidin-3-yl)nicotinamide;

[0262] 6-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0263] 6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-N-((1R,3R)-3-hydroxycyclopentyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0264] 6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-N-((1R,3S)-3-hydroxycyclopentyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0265] 6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-N-(3-hydroxycyclobutyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0266] 6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-N-((1R,2R)-2-hydroxycyclobutyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0267] N-(3,3-difluorocyclobutyl)-6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0268] N-((1R,3R)-3-aminocyclopentyl)-6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0269] N-((1R,3S)-3-aminocyclopentyl)-6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0270] 6-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-N-((1R,3R)-3-hydroxycyclopentyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0271] 6-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-N-((1R,3S)-3-hydroxycyclopentyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0272] 6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)-N-((R)-1-methylpyrrolidin-3-yl)nicotinamide;

[0273] N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0274] N-(4-((3S,5S)-3-amino-5-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0275] (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0276] N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0277] N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0278] (3R,4R)-3-amino-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-ol;

[0279] N-(4-((3S,5S)-3-amino-5-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0280] N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0281] (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0282] (3R,4R)-3-amino-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-ol;

[0283] (1S,4S)-4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)(methyl)amino)cyclohexan-1-ol;

[0284] N2-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0285] N2-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0286] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0287] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0288] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0289] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0290] (3S)-1-(5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-2-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0291] (3S)-1-(5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)-2-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0292] (3S)-1-(2-((6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0293] (3S)-1-(2-((6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0294] (3S)-1-(2-((6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0295] (3S)-1-(2-((5-amino-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0296] (3S)-1-(2-((5-amino-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0297] (3S)-1-(2-((5-amino-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(2-(tetrahydro-2H-pyran-4-yl)ethyl)pyridin-4-yl)piperidin-3-ol;

[0298] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-methoxy-2-methylpropyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0299] (S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(2-methoxyethoxy)-[3,3'-bipyridin]-6-amine;

[0300] (S)-(3,3-difluoroazetidin-1-yl)(4-(4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)methanone;

[0301] (4-(4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)((S)-3-fluoropyrrolidin-1-yl)methanone;

[0302] (4-(4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)((R)-3-fluoropyrrolidin-1-yl)methanone;

[0303] (S)-(4-(4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)(3,3-difluoropyrrolidin-1-yl)methanone;

[0304] (S)-1-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)-2-methylpropan-2-ol;

[0305] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0306] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(azetidin-3-ylmethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0307] N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-((R)-pyrrolidin-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0308] N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-((S)-pyrrolidin-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0309] (S)-4-(3-aminopiperidin-1-yl)-N6'-(2-(dimethylamino)ethyl)-N6-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-[3,3'-bipyridin]-6,6'-diamine;

[0310] (S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(piperazin-1-yl)-[3,3'-bipyridin]-6-amine;

[0311] (S)-(2-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluorophenyl)methanol;

[0312] (S)-(2-(4-((4-(3-aminopiperidin-1-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluorophenyl)methanol;

[0313] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(1-methoxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0314] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-((3,3-difluorocyclobutyl)methyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0315] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0316] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(fluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0317] (S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(piperidin-4-yl)-[3,3'-bipyridin]-6-amine;

[0318] (S)-4-(3-aminopiperidin-1-yl)-6'-(2-(dimethylamino)ethoxy)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-[3,3'-bipyridin]-6-amine;

[0319] (S)-1-(4'-(3-aminopiperidin-1-yl)-6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-[3,3'-bipyridin]-6-yl)-3-ethylurea;

[0320] (4-(4-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)((R)-3-fluoropyrrolidin-1-yl)methanone;

[0321] N-(4-((2R,5S)-5-amino-2-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0322] N-(4-((3R,4S)-3-amino-4-methoxypiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0323] N-(4-((3R,4R)-3-amino-4-methoxypiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0324] (S)-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)(morpholino)methanone;

[0325] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0326] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0327] (S)-6-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one;

[0328] (S)-1-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)pyrrolidin-2-one;

[0329] (S)-7-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one;

[0330] (S)-7-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-4-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one;

[0331] (S)-6-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-8-methyl-3,4-dihydroquinolin-2(1H)-one;

[0332] (S)-6-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1-methyl-3,4-dihydroquinolin-2(1H)-one;

[0333] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0334] (S)-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)(piperazin-1-yl)methanone;

[0335] (S)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-((methylamino)methyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0336] (R)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-((methylamino)methyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0337] N-(4-((3R,4R)-4-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0338] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0339] 6-(4-((S)-3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one;

[0340] (S)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-methylpiperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0341] (S)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-(fluoromethyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0342] (R)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-(difluoromethyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0343] (S)-7-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-4-methyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one;

[0344] (S)-7-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one;

[0345] (S)-6-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one;

[0346] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0347] methyl (S)-2-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)-2-methylpropanoate;

[0348] (S)-N-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)acetamide;

[0349] (S)-3-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-N,N-dimethylbenzamide;

[0350] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(3-methyl-4-(trifluoromethoxy)phenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0351] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-fluoro-3-methylphenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0352] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0353] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-isopropoxy-3,5-dimethylphenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0354] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-methoxy-3,5-dimethylphenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0355] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-morpholinophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0356] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(3-methyl-4-morpholinophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0357] (S)-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)(4-(2-hydroxyethyl)piperazin-1-yl)methanone;

[0358] 4-(4-((S)-3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-N-((1r,4S)-4-hydroxycyclohexyl)benzamide;

[0359] (S)-4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2-fluoro-N,N-dimethylbenzamide;

[0360] (S)-1-(3-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)ethan-1-one;

[0361] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(3-chloro-4-fluorophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0362] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-fluoro-3-(trifluoromethyl)phenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0363] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(3,4-difluorophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0364] (3R,4R)-4-amino-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0365] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(3-(dimethylamino)-4-fluorophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0366] N-(4-((3R,4S)-4-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0367] N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-((S)-tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0368] N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-((R)-tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0369] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0370] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0371] N-(4-((3S,4S)-4-amino-3-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0372] N-(4-((3S,5R)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0373] N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0374] N-(4-((3S,5R)-3-amino-5-(trifluoromethyl)piperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0375] (3S,5S)-5-amino-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0376] N-(4-((3R,4S)-4-amino-3-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0377] N-(4-((3S,4R)-4-amino-3-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0378] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;

[0379] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;

[0380] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((4-methyltetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0381] (S)-4-((4-(3-aminopiperidin-1-yl)-6-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)ethynyl)tetrahydro-2H-pyran-4-ol;

[0382] (S)-4-(4-(3-aminopiperidin-1-yl)-6-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2-methylbut-3-yn-2-ol;

[0383] (S)-4-(4-(3-aminopiperidin-1-yl)-6-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)but-3-yn-1-ol;

[0384] 4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-(methylsulfonyl)pyridin-2-yl)pyridin-2-amine;

[0385] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinonitrile;

[0386] 2-(2,4-difluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinonitrile;

[0387] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0388] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0389] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;

[0390] 6-((4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0391] 6-((4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0392] 6-((4-((S)-3-aminopiperidin-1-yl)-6'-morpholino-[3,3'-bipyridin]-6-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0393] N-(4-((3S,5R)-3-amino-5-fluoropiperidin-1-yl)-5-(2-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0394] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinonitrile;

[0395] 6-((4-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0396] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-ethyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0397] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0398] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-cyclopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0399] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0400] 6-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((3R,4R)-4-fluoro-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0401] N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0402] N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0403] 4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)pyridin-2-amine;

[0404] N-(4-((3S,5R)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0405] N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0406] 6-((4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)-nicotinonitrile;

[0407] 6-((4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;

[0408] N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0409] 6-((4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile; and

[0410] 4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)pyridin-2-amine.

[0411] In the compound of Formula 1 or pharmaceutically acceptable salt, more preferable compounds include the following compound or pharmaceutically acceptable salt thereof selected from the group consisting of:

[0412] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0413] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0414] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0415] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0416] (3S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0417] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0418] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0419] (S)-1-(5-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0420] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(4-(tetrahydro-2H-pyran-4-yl)phenyl)pyridin-4-yl)piperidin-3-ol;

[0421] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(4-(4-methylpiperazin-1-yl)phenyl)pyridin-4-yl)piperidin-3-ol;

[0422] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-morpholino-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0423] (S)-1-(2-((2-(2,6-difluorophenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0424] (S)-1-(2-((2-(2,3-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0425] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0426] (S)-(6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(4-hydroxypiperidin-1-yl)methanone;

[0427] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-(((S)-3-fluoropyrrolidin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0428] (3S)-1-(2-((5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0429] (3S)-1-(2-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0430] N-(4-(4-((dimethylamino)methyl)-4-fluoropiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0431] (4-(2,2-difluoroethyl)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)methanol;

[0432] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0433] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinonitrile;

[0434] methyl 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinate;

[0435] N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0436] 1-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)cyclopropan-1-ol;

[0437] 1-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;

[0438] 2-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol;

[0439] (S)-1-(2-((2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0440] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine;

[0441] methyl 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinate;

[0442] (S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0443] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0444] (3S)-1-(2-((5-chloro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0445] 4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)pyridin-2-amine;

[0446] (R)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0447] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0448] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0449] 2-(2-fluoro-6-methoxyphenyl)-N-(4-(3-(fluoromethyl)piperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;

[0450] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-amine;

[0451] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0452] (3R,4R)-4-fluoro-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0453] (3R,4R)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-(hydroxymethyl)piperidin-3-ol;

[0454] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0455] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0456] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0457] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0458] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinamide;

[0459] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0460] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0461] N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0462] 2-(2-fluoro-6-methoxyphenyl)-N-(4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;

[0463] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)amino)nicotinamide;

[0464] 6-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinamide;

[0465] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinamide;

[0466] (3S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0467] 4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)pyridin-2-amine;

[0468] (3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0469] N²-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0470] 4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)pyridin-2-amine;

[0471] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-amine;

[0472] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-amine;

[0473] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-amine;

[0474] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0475] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0476] (S)-1-(2-((2-(2-fluoro-4-(hydroxymethyl)-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0477] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0478] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0479] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0480] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0481] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0482] N2-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0483] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0484] (3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0485] (3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0486] (3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0487] (3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0488] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0489] (3S)-1-(2-((6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0490] (3S)-1-(2-((5-amino-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0491] methyl (S)-4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxybenzoate;

[0492] (S)-4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxy-N,N-dimethylbenzamide;

[0493] (S)-3-fluoro-4-(4-((4-(3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-5-methoxybenzaldehyde;

[0494] 6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-N-((1R,2R)-2-hydroxycyclobutyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;

[0495] N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0496] N-(4-((3S,5S)-3-amino-5-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0497] (S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0498] N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0499] N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0500] (3R,4R)-3-amino-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-ol;

[0501] N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0502] (3R,4R)-3-amino-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-ol;

[0503] (1S,4S)-4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)(methyl)amino)cyclohexan-1-ol;

[0504] N2-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0505] N2-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0506] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0507] (S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;

[0508] (3S)-1-(2-((6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0509] (3S)-1-(2-((6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0510] (3S)-1-(2-((5-amino-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0511] (3S)-1-(2-((5-amino-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0512] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-methoxy-2-methylpropyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0513] (S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(2-methoxyethoxy)-[3,3'-bipyridin]-6-amine;

[0514] (S)-(3,3-difluoroazetidin-1-yl)(4-(4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)methanone;

[0515] (4-(4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)((R)-3-fluoropyrrolidin-1-yl)methanone;

[0516] (S)-(4-(4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)(3,3-difluoropyrrolidin-1-yl)methanone;

[0517] (S)-1-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)-2-methylpropan-2-ol;

[0518] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(1-methoxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0519] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-((3,3-difluorocyclobutyl)methyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0520] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(fluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0521] N-(4-((2R,5S)-5-amino-2-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0522] N-(4-((3R,4S)-3-amino-4-methoxypiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0523] N-(4-((3R,4R)-3-amino-4-methoxypiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0524] (S)-7-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-4-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one;

[0525] (S)-6-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-8-methyl-3,4-dihydroquinolin-2(1H)-one;

[0526] (S)-6-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1-methyl-3,4-dihydroquinolin-2(1H)-one;

[0527] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0528] (S)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-((methylamino)methyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0529] (R)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-((methylamino)methyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0530] N-(4-((3R,4R)-4-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0531] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0532] (S)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-(fluoromethyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0533] (R)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-(difluoromethyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0534] methyl (S)-2-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)-2-methylpropanoate;

[0535] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-methoxy-3,5-dimethylphenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0536] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-morpholinophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0537] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(3-methyl-4-morpholinophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0538] (S)-4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2-fluoro-N,N-dimethylbenzamide;

[0539] (S)-1-(3-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)ethan-1-one;

[0540] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(3,4-difluorophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0541] (3R,4R)-4-amino-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0542] N-(4-((3R,4S)-4-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0543] N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-((S)-tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0544] N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-((R)-tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0545] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0546] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0547] N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0548] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;

[0549] (S)-4-(4-(3-aminopiperidin-1-yl)-6-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2-methylbut-3-yn-2-ol;

[0550] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;

[0551] 6-((4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile; and

[0552] 6-((4-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile.

[0553] In the compound of Formula 1 or pharmaceutically acceptable salt, still more preferable compounds include the following compound or pharmaceutically acceptable salt thereof selected from the group consisting of:

[0554] (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0555] (S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;

[0556] (3S)-1-(2-((5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0557] (3S)-1-(2-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0558] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0559] methyl 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinate;

[0560] (S)-1-(2-((2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0561] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine;

[0562] (S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0563] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0564] 4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)pyridin-2-amine;

[0565] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0566] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0567] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0568] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0569] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0570] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0571] 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinamide;

[0572] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0573] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0574] 6-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinamide;

[0575] 4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)pyridin-2-amine;

[0576] (3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;

[0577] 4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)pyridin-2-amine;

[0578] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-amine;

[0579] 4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-amine;

[0580] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0581] (S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0582] N2-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0583] (S)-4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxy-N,N-dimethylbenzamide;

[0584] (3R,4R)-3-amino-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-ol;

[0585] N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0586] (3R,4R)-3-amino-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-ol;

[0587] N2-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0588] N2-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2,5-diamine;

[0589] (S)-1-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)-2-methylpropan-2-ol;

[0590] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(fluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0591] N-(4-((3R,4R)-4-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0592] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0593] (S)-N-(4-(3-aminopiperidin-1-yl)-5-(3,4-difluorophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0594] (3R,4R)-4-amino-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;

[0595] N-(4-((3R,4S)-4-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0596] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;

[0597] N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;

[0598] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;

[0599] (S)-4-(4-(3-aminopiperidin-1-yl)-6-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2-methylbut-3-yn-2-ol;

[0600] 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;

[0601] 6-((4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile; and

[0602] 6-((4-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile.

[0603] The compound of Formula 1 or pharmaceutically acceptable salt thereof may be in the form of structural isomer such as tautomer and in the form of stereoisomer such as R or S isomer having with asymmetric carbon center(s), cis- or trans-geometrical isomer, or optical isomer (enantiomer). Therefore, the compound of Formula 1 or pharmaceutically acceptable salt thereof includes said all forms, such as a cis- or trans-geometrical isomer, a (R)- or (S)-optical isomer, and a racemic mixture (RS), unless otherwise indicated.

[0604] The compound of Formula 1 of the present invention may be in a pharmaceutically acceptable salt form. The salt may be a conventional acid addition salt form, which includes e.g., salts derived from an inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, or hydrobromic acid; and salts derived from an organic acid such as formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, citric acid, maleic acid, malonic acid, malic acid, tartaric acid, gluconic acid, lactic acid, gentisic acid, fumaric acid, lactobionic acid, salicylic acid, phthalic acid, embonic acid, aspartic acid, glutamic acid, or acetylsalicylic acid. And, the salt includes a salt derived from amino acids such as glycine, alanine, valine, isoleucine, serine, cysteine, cystine, aspartic acid, glutamine, lysine, arginine, tyrosine, and proline. In addition, the salt includes a salt derived from sulfonic acids, such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, or toluenesulfonic acid.

[0605] The present invention includes, within its scope, a process for preparing the compound of Formula 1 or pharmaceutically acceptable salt thereof.

[0606] For example, the compound of Formula 1 or pharmaceutically acceptable salt thereof according to the present invention may be prepared by a process which comprises preparing a compound of Formula IV from a compound of Formula II, via a compound of Formula III-a or III-b, through Synthesis 1 or Synthesis 2; and reacting the compound of Formula IV with a compound of Formula V through Synthesis 3 to prepare a compound of Formula 1, as shown in the following Reaction Scheme 1:

[0607] <Reaction Scheme 1>

[0608]

[0609] In the Reaction Scheme 1, hal is halogen; M is -B(OH)2or pinacolborane (-BPin); and P1, P2, R1, R2, L, Q, Y, X, and A are the same as defined in the above.

[0610] In the Reaction Scheme 1, the reaction of Synthesis 1 may be carried out by reacting the commercially available compound of Formula II or III-b with NHR1R2. The reaction may be carried out with a base such as cesium carbonate (Cs2CO3), potassium carbonate (K2CO3), triethylamine (TEA), or diisopropylethylamine (DIPEA), in an organic solvent such as dimethylformamide, acetonitrile, dichloromethane, or dimethyl sulfoxide. And, the reaction may be carried out at room temperature or under heating conditions (60 ℃ to 110 ℃), but is not limited thereto.

[0611] In the Reaction Scheme 1, the reaction of Synthesis 2 may be carried out by reacting the compound of Formula II or III-a having the substituent M with Y-Q-L-halide or reacting the compound of Formula II or III-a having the substituent hal with Y-Q-L-B(OH)2or pinacolborane.

[0612] The reaction of Synthesis 2 may be carried out through the Suzuki reaction, using a palladium catalyst. The palladium catalyst includes palladium diacetate (Pd(OAc)2), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride (PdCl2(dppf)2), or dichlorobis(triphenylphosphine)palladium(II) (PdCl2(PPh3)2), etc. And, the reaction may be carried out in the presence of a base such as cesium carbonate (Cs2CO3) or potassium carbonate (K2CO3), in an organic solvent such as 1,4-dioxane, tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane, or dimethylformamide and water, at 80 ℃ to 110 ℃.

[0613] In addition, the reaction of Synthesis 2 may be also carried out through the Sonogashira reaction using a palladium and copper catalyst. The palladium and copper catalyst includes e.g., tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), dichlorobis(triphenylphosphine)palladium(II) (PdCl2(PPh3)2), and copper(I) iodide (CuI). And, the reaction may be carried out in the presence of a base such as triethylamine (TEA) or diisopropylethylamine (DIPEA), in an organic solvent such as dimethylformamide or tetrahydrofuran, at 60 ℃ to 110 ℃.

[0614] In the Reaction Scheme 1, the reaction of Synthesis 3 may be carried out by reacting the compound of Formula IV with the compound of Formula V, using a palladium catalyst, through the Buchwald-hartwig reaction. The palladium catalyst includes palladium diacetate (Pd(OAc)2), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), or palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride (PdCl2(dppf)2), etc. The reaction may be carried out using a ligand and a base, in addition to the palladium catalyst. The ligand includes 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), (S)-2,2-bis(diphenylphosphino)-1,1-binaphthyl (BINAP), or 1,1'-bis(diphenylphosphino)ferrocene (dppf), etc. The base includes cesium carbonate (Cs2CO3), potassium carbonate (K2CO3), potassium fluoride (KF), potassium phosphate (K3PO4), sodium tert-butoxide (NaOtBu), etc. The reaction may be carried out in an organic solvent such as benzene, toluene, 1,4-dioxane, tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane, or dimethylformamide, at 60 ℃ to 110 ℃.

[0615] The compound of Formula V in the Reaction Scheme 1 may be prepared from e.g., a compound of Formula Va, according to the following Reaction Scheme 2.

[0616] <Reaction Scheme 2>

[0617]

[0618] In the Reaction Scheme 2, hal is halogen and X and A are the same as defined in the above.

[0619] In the Reaction Scheme 2, the reaction of Synthesis 4 may be carried out by reacting the compound of Formula Va with A-boronic acid or A-pinacolborane through the Suzuki reaction, using a palladium catalyst. The palladium catalyst includes palladium diacetate (Pd(OAc)2), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride (PdCl2(dppf)2), or dichlorobis(triphenylphosphine)palladium(II) (PdCl2(PPh3)2), etc. And, the reaction may be carried out in the presence of a base such as cesium carbonate (Cs2CO3) or potassium carbonate (K2CO3), in an organic solvent such as 1,4-dioxane, tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane, or dimethylformamide and water, at 80 ℃ to 110 ℃.

[0620] The pyrimidine / pyridine derivative or pharmaceutically acceptable salt thereof according to the present invention, i.e., the compound of Formula 1 or pharmaceutically acceptable salt thereof has an excellent inhibitory activity against hematopoietic progenitor kinase 1 (HPK1) and thus can be usefully applied for the prevention or treatment of various diseases mediated by HPK1.

[0621] Therefore, the present invention includes, within its scope, a pharmaceutical composition for inhibiting hematopoietic progenitor kinase 1 comprising a therapeutically effective amount of the compound of Formula 1 or pharmaceutically acceptable salt thereof as an active ingredient. In an embodiment, the present invention provides a pharmaceutical composition for preventing or treating the diseases associated with HPK1 such as a cancer including a blood cancer or a solid tumor, for example melanoma, blastoma, sarcoma, lymphoma, leukemia, bladder cancer, brain tumor, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, endometrioma, hepatic cancer, laryngeal cancer, lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, thyroid cancer, ependymoma, glioblastoma, bullous cell tumor, neuroblastoma, osteosarcoma, rhabdomyosarcoma, or nephroblastoma, comprising a therapeutically effective amount of the compound of Formula 1 or pharmaceutically acceptable salt thereof as an active ingredient.

[0622] The pharmaceutical composition of the present invention may comprise a pharmaceutically acceptable carrier, such as diluents, disintegrants, sweeteners, lubricants, or flavoring agents, which is conventionally used in the art. The pharmaceutical composition may be formulated to an oral dosage form such as tablets, capsules, powders, granules, suspensions, emulsions, or syrups; or a parenteral dosage form such as solutions for external use, suspensions for external use, emulsions for external use, gels (e.g., ointment), inhalations, nebulizations, injections, according to conventional methods. The dosage form may be formulated to various forms, e.g., dosage forms for single administration or for multiple administrations.

[0623] The pharmaceutical composition of the present invention may comprise, for example, a diluent (e.g., lactose, corn starch, etc.); a lubricant (e.g., magnesium stearate); an emulsifying agent; a suspending agent; a stabilizer; and / or an isotonic agent. If necessary, the composition further comprises sweeteners and / or flavoring agents.

[0624] The composition of the present invention may be administered orally or parenterally, including inhalant, intravenous, intraperitoneal, subcutaneous, rectal and topical routes of administration. Therefore, the composition of the present invention may be formulated into various forms such as tablets, capsules, aqueous solutions or suspensions. In the case of tablets for oral administration, carriers such as lactose, corn starch, and lubricating agents, e.g. magnesium stearate, are conventionally used. In the case of capsules for oral administration, lactose and / or dried corn starch can be used as a diluent. When an aqueous suspension is required for oral administration, the active ingredient may be combined with emulsifying and / or suspending agents. If desired, certain sweetening and / or flavoring agents may be used. For intramuscular, intraperitoneal, subcutaneous and intravenous administration, sterile solutions of the active ingredient are usually prepared, and the pH of the solutions should be suitably adjusted and buffered. For intravenous administration, the total concentration of solutes should be controlled in order to render the preparation isotonic. The composition of the present invention may be in the form of an aqueous solution containing pharmaceutically acceptable carriers, e.g., saline having a pH level of 7.4. The solutions may be introduced into a patient's intramuscular bloodstream by local bolus injection.

[0625] The compound of Formula 1 or pharmaceutically acceptable salt thereof may be singly or multiply administered in an effective amount ranging from about 1 mg / kg per day to about 1000 mg / kg per day, preferably from about 100 mg / kg per day to about 800 mg / kg per day, to a subject patient. Of course, the dosage may be changed according to the patient's age, weight, susceptibility, symptom, or activity of the compound.

[0626] The present invention includes, within its scope, a method for inhibiting hematopoietic progenitor kinase 1 in a mammal, comprising administering a therapeutically effective amount of the compound of Formula 1 or pharmaceutically acceptable salt thereof to the mammal in need thereof. In an embodiment, the present invention provides a method for treating the diseases associated with HPK1 such as a cancer including a blood cancer or a solid tumor, for example melanoma, blastoma, sarcoma, lymphoma, leukemia, bladder cancer, brain tumor, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, endometrioma, hepatic cancer, laryngeal cancer, lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, thyroid cancer, ependymoma, glioblastoma, bullous cell tumor, neuroblastoma, osteosarcoma, rhabdomyosarcoma, or nephroblastoma, comprising administering a therapeutically effective amount of the compound of Formula 1 or pharmaceutically acceptable salt thereof to the mammal in need thereof.

[0627] The present invention also provides a use of the compound of Formula 1 or pharmaceutically acceptable salt thereof for the manufacture of a medicament for inhibiting hematopoietic progenitor kinase 1 in a mammal. In an embodiment, the present invention provides a use of the compound of Formula 1 or pharmaceutically acceptable salt thereof for the manufacture of a medicament for preventing or treating the diseases associated with HPK1 such as a cancer including a blood cancer or a solid tumor, for example melanoma, blastoma, sarcoma, lymphoma, leukemia, bladder cancer, brain tumor, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, endometrioma, hepatic cancer, laryngeal cancer, lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, thyroid cancer, ependymoma, glioblastoma, bullous cell tumor, neuroblastoma, osteosarcoma, rhabdomyosarcoma, or nephroblastoma.

[0628] Hereinafter, the present invention will be described in more detail through examples and test examples. However, these examples and test examples are provided for illustration purposes only and are not intended to limit the scope of the invention.

[0629] The analyses of the compounds prepared below were carried out as follows: Nuclear magnetic resonance (NMR) spectrum analysis was carried out using Bruker 400 MHz spectrometer and the chemical shifts thereof were analyzed in ppm. And, the indicated molecular weights were measured by using liquid chromatograph / mass selective detector (MSD) of Agilent 1260 Infinity series equipped with an electrostatic spray interface, which depicts the m / z ratio values in ESI+ (electrospray ionization (cation)) by using Single Quadrupole, with the [M+H]+ peak represented. The purification of the compounds synthesized below was carried out with medium pressure liquid chromatography (MPLC) using the CombiFlash NextGen 300+ (Teledyne ISCO, USA). In addition, the starting materials for each example were known compounds that were synthesized according to literatures or purchased from the commercial markets.

[0630] The following Preparations show the methods for synthesizing the intermediates for preparing the compounds or salts thereof of the present invention (i.e., the compounds of Examples).

[0631] Preparation A1-1: (S)-(6-((2-chloropyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)(cyclopropyl)methanone

[0632] Step 1: (S)-(6-chloro-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)(cyclopropyl)methanone

[0633] Cyclopropyl(4,6-dichloropyridin-3-yl)methanone (3.0 g, 13.89 mmol) was dissolved in anhydrous acetonitrile (70.0 mL) and then (S)-3-hydroxypiperidine hydrochloride (2.1 g, 15.27 mmol) and diisopropylethylamine (3.8 mL, 27.77 mmol) were added dropwise thereto. The reaction mixture was stirred at room temperature overnight. Water was added to the reaction mixture and then the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (2.24 g). (Yield: 57.4%) 1H NMR (CDCl3, 400MHz) δ 8.34 (s, 1H), 6.85 (s, 1H), 3.93-3.38 (m, 1H), 3.36-3.35 (m, 1H), 3.19-3.17 (m, 1H), 3.12-3.05 (m, 2H), 2.54-2.51 (m, 1H), 1.96-1.92 (m, 2H), 1.65-1.62 (m, 2H), 1.31-1.30 (m, 2H), 1.29-1.28 (m, 2H)

[0634] Step 2: (S)-(6-((2-chloropyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)(cyclopropyl)methanone (A1-1)

[0635] (S)-(6-Chloro-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)(cyclopropyl)methanone (1.0 g, 23.56 mmol) was dissolved in anhydrous 1,4-dioxane (24.0 mL) and then 4-amino-2-chloropyrimidine (507.6 mg, 3.92 mmol), tris(dibenzylideneacetone)dipalladium (326.2 mg, 3.92 mmol), and 4 5-bis(diphenylphosphino)-9 9-dimethylxanthene (412.2 mg, 0.71 mmol) were added dropwise thereto. Then, 1.0M lithium bis(trimethylsilyl)amide (7.1 mL, 7.12 mmol) dissolved in tetrahydrofuran was added to the mixed solution, which was then refluxed under stirring at 110℃ for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (400.0 mg). (Yield: 30.0%) 1H NMR (CDCl3, 400MHz) δ 8.39 (s, 1H), 8.32 (d, 1H), 7.45 (d, 1H), 7.3 (s, 1H), 3.97 (s, 1H), 3.44-3.43 (m, 1H), 3.27-3.24 (m, 1H), 3.23-3.10 (m, 2H), 2.63-2.60 (m, 1H), 2.59-2.41 (m, 1H), 2.01-1.91 (m, 2H), 1.70-1.58 (m, 2H), 1.32-1.25 (m, 2H), 1.07-1.04 (m, 2H)

[0636] Preparation A1-2: (3S)-1-[2-[(2-chloropyrimidin-4-yl)amino]-5-(1-tetrahydropyran-4-ylpyrazol-4-yl)-4-pyridyl]piperidin-3-ol

[0637] (S)-1-(2-Chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol (A2-1) was dissolved in anhydrous 1,4-dioxane (27.0 mL) and then 4-amino-2-chloropyrimidine (1.07 g, 8.27 mmol), tris(dibenzylideneacetone)dipalladium (504.7 mg, 0.55 mmol), 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl (514.4 mg, 1.10 mmol), and sodium tert-butoxide (794.5 mg, 8.27 mmol) were added thereto. The reaction mixture was refluxed under stirring at 110℃ overnight. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (317.0 mg). (Yield: 25.2%) 1H NMR (CDCl3, 400MHz) δ 8.26 (s, 1H), 8.16 (s, 1H), 8.06 (d, 1H), 7.83 (s, 1H), 6.99 (s, 1H), 6.06 (d, 1H), 4.46-4.44 (m, 1H), 4.21-4.13 (m, 3H), 3.62-3.54 (m, 3H), 3.11-3.05 (m, 1H), 2.94-2.84 (m, 2H), 2.52-2.34 (m, 1H), 2.28-2.01 (m, 4H), 2.05-1.86 (m, 2H), 1.84-1.16 (m, 2H)

[0638] Preparation A2-1: (S)-1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0639] Step 1: (S)-1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-ol (A2)

[0640] 2-Chloro-4-fluoro-5-iodopyridine (1.0 g, 3.88 mmol) was dissolved in anhydrous dimethylformamide (20.0 mL) and then (S)-3-hydroxypiperidine hydrochloride (588.0 mg, 4.27 mmol) and diisopropylethylamine (1.6 mL, 11.65 mmol) were added dropwise thereto. The reaction mixture was stirred at 50℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (800 mg). (Yield: 60.8%) 1H NMR (CDCl3, 400MHz) δ 8.57 (s, 1H), 6.87 (s, 1H), 4.04-3.99 (m, 1H), 3.34-3.31 (m, 1H), 3.07-3.04 (m, 2H), 3.01-2.96 (m, 1H), 2.24 (d, 1H), 2.06-1.99 (m, 1H), 1.92-1.86 (m, 1H), 1.80-1.73 (m, 2H)

[0641] Step 2: (S)-1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol (A2-1)

[0642] (S)-1-(2-Chloro-5-iodopyridin-4-yl)piperidin-3-ol (2.1 g, 6.29 mmol) was dissolved in anhydrous 1,4-dioxane (31.4 mL) and then 1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-boronic acid pinacol ester (1.75 g, 6.29 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (257.0 mg, 0.31 mmol), 2.0M sodium carbonate solution (10.0 mL, 20.0 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 80℃ for 6 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (1.61 g). (Yield: 70.3%) 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 7.80 (d, 2H), 6.88 (s, 1H), 4.44-4.37 (m, 1H), 4.16-4.13 (m, 2H), 3.87-3.82 (m, 1H), 3.61-3.54 (m, 2H), 3.26-3.23 (m, 1H), 3.01-2.98 (m, 1H), 2.78-2.69 (m, 2H), 2.18-2.05 (m, 4H), 1.94-1.91 (m, 1H), 1.84-1.80 (m, 1H), 1.66-1.49 (m, 3H)

[0643] Preparation A2-2: (S)-1-(2-chloro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0644] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 1-methylpyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.11 (s, 1H), 7.78 (s, 1H), 7.67 (s, 1H), 6.87 (s, 1H), 3.97 (s, 3H), 3.86-3.72 (m, 1H), 3.27-3.25 (m, 1H), 3.03-3.00 (m, 1H), 2.78-2.66 (m, 2H), 1.95-1.92 (m, 1H), 1.82-1.80 (m, 1H), 1.79-1.65 (m, 1H), 1.50-1.48 (m, 1H)

[0645] Preparation A2-3: (S)-1-(2-chloro-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0646] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 1-isopropylpyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.76 (s, 2H), 6.86 (s, 1H), 4.58 (septet, 1H), 3.92-3.85 (m, 1H), 3.27-3.24 (m, 1H), 3.01-2.98 (m, 1H), 2.76-2.66 (m, 2H), 1.94-1.91 (m, 1H), 1.87-1.82 (m, 1H), 1.81-1.79 (m, 1H), 1.68 (d, 6H), 1.52-1.50 (m, 1H)

[0647] Preparation A2-4: (3S)-1-(2-chloro-5-(1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0648] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 1-(oxolan-3-yl)-1H-pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.13 (s, 1H), 7.84 (s, 1H), 7.78 (s, 1H), 6.87 (s, 1H), 5.05-5.04 (m, 1H), 4.18-4.12 (m, 3H), 4.07-4.04 (m, 1H), 3.99-3.93 (m, 1H), 3.84-3.72 (m, 1H), 3.24-3.21 (m, 1H), 3.00-2.98 (m, 1H), 2.78-2.69 (m, 2H), 2.55-2.48 (m, 1H), 2.40-2.36 (m, 1H), 1.93-1.90 (m, 1H), 1.81-1.72 (m, 1H), 1.69-1.67 (m, 1H), 1.51-1.49 (m, 1H)

[0649] Preparation A2-5: (S)-1-(2-chloro-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0650] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.88 (d, 2H), 6.91 (s, 1H), 4.82-4.76 (m, 2H), 3.88-3.85 (m, 1H), 3.28-3.24 (m, 1H), 3.03-2.99 (m, 1H), 2.78-2.69 (m, 2H), 1.98-1.94 (m, 1H), 1.84-1.80 (m, 1H), 1.64-1.62 (m, 1H), 1.56-1.49 (m, 2H)

[0651] Preparation A2-6: (S)-1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0652] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.13 (s, 1H), 7.96 (s, 2H), 6.89 (s, 1H), 4.80-4.74 (q, 2H), 3.85-3.84 (m, 1H), 3.26-3.23 (m, 1H), 3.01-2.98 (m, 1H), 2.76-2.67 (m, 2H), 1.95-1.92 (m, 1H), 181-1.79 (m, 1H), 1.62-1.60 (m, 1H), 1.50-1.47 (m, 1H)

[0653] Preparation A2-7: (S)-1-(2-chloro-5-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0654] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 1-(cyclopropylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 7.85 (s, 1H), 7.77 (s, 1H), 6.87 (s, 1H), 4.05 (d, 2H), 3.92-3.86 (m, 1H), 3.28-3.25 (m, 1H), 3.03-3.00 (m, 1H), 2.78-2.67 (m, 2H), 1.94-1.91 (m, 1H), 1.82-1.80 (m, 1H), 1.75-1.71 (m, 1H), 1.55-1.54 (m, 2H), 1.52-1.50 (m, 1H), 0.92-0.71 (m, 2H), 0.69-0.68 (m, 2H)

[0655] Preparation A2-8: (S)-1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0656] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.18 (d, 2H), 7.99 (s, 1H), 7.26 (t, 1H), 6.93 (s, 1H), 3.91-3.86 (m, 1H), 3.27-3.23 (m, 1H), 3.04-2.99 (m, 1H), 3.80 (s, 2H), 2.07-1.94 (m, 1H), 1.88-1.82 (m, 1H), 1.63-1.62 (m, 1H), 1.55-1.50 (m, 2H)

[0657] Preparation A2-9: (S)-1-(2-chloro-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0658] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 1-(2-methoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.16 (s, 1H), 7.91 (s, 1H), 7.78 (s, 1H), 6.88 (s, 1H), 4.37-4.31 (m, 2H), 3.87-3.78 (m, 3H), 3.39 (s, 3H), 3.14 (d, 1H), 3.04-2.99 (m, 1H), 2.86-2.81 (m, 1H), 2.78-2.73 (m, 1H), 1.90-1.88 (m, 2H), 1.71-1.68 (m, 1H), 1.58-1.53 (m, 1H)

[0659] Preparation A2-10: (S)-1-(2-chloro-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0660] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 1-(2,2-difluoroethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.86-7.85 (m, 2H), 6.91 (s, 1H), 6.32-6.02 (m, 1H), 4.58-4.50 (m, 2H), 3.90-3.84 (m, 1H), 3.27-3.23 (m, 1H), 3.04-3.00 (m, 1H), 2.79-2.67 (m, 2H), 1.98-1.94 (m, 1H), 1.86-1.80 (m, 1H), 1.57-1.48 (m, 3H)

[0661] Preparation A2-11: (S)-1-(2-chloro-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[0662] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(trifluoromethyl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 7.83 (s, 1H), 7.76 (s, 1H), 6.85 (s, 1H), 4.58-4.52 (m, 1H), 4.37-4.35 (m, 2H), 3.81-3.79 (m, 3H), 3.40-3.35 (m, 4H), 3.05-3.02 (m, 1H), 2.61-2.56 (m, 1H), 1.93-1.92 (m, 1H), 1.65-1.63 (m, 1H), 1.46 (s, 9H), 1.41-1.31 (m, 1H)

[0663] Preparation A2-12: (S)-1-(2-chloro-5-(4-(tetrahydro-2H-pyran-4-yl)phenyl)pyridin-4-yl)piperidin-3-ol

[0664] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 4-(4-tetrahydropyranyl)phenylboronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.44-7.42 (m, 2H), 7.32-7.30 (m, 2H), 6.86 (s, 1H), 4.12-4.10 (m, 2H), 3.71-3.70 (m, 1H), 3.59-3.53 (m, 2H), 3.13-3.11 (m, 1H), 2.92-2.90 (m, 1H), 2.84-2.70 (m, 3H), 1.87-1.82 (m, 5H), 1.79-1.68 (m, 1H), 1.56-1.44 (m, 3H)

[0665] Preparation A2-13: (S)-1-(2-chloro-5-(4-(4-methylpiperazin-1-yl)phenyl)pyridin-4-yl)piperidin-3-ol

[0666] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 4-(4-methyl-1-piperazinyl)phenylboronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.01 (s, 1H), 7.39 (d, 2H), 7.00 (d, 2H), 6.84 (s, 1H), 3.82-3.74 (m, 1H), 3.30-3.27 (m, 4H), 3.16-3.13 (m, 1H), 2.94-2.92 (m, 1H), 2.79-2.71 (m, 2H), 2.63-2.61 (m, 4H), 2.38 (s, 3H), 1.74-1.70 (m, 2H), 1.48-1.46 (m, 2H)

[0667] Preparation A2-14: (S)-1-(6-chloro-6'-morpholino-[3,3'-bipyridin]-4-yl)piperidin-3-ol

[0668] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 6-(morpholin-4-yl)pyridin-3-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.31 (s, 1H), 8.00 (s, 1H), 7.71 (d, 1H), 6.87 (s, 1H), 6.72 (d, 1H), 3.86-3.84 (m, 4H), 3.78-3.77 (m, 1H), 3.58-3.55 (m, 4H), 3.23-3.21 (m, 1H), 3.01-2.99 (m, 1H), 2.80-2.69 (m, 2H), 1.92-1.87 (m, 1H), 1.82-1.72 (m, 1H), 1.49-1.45 (m, 2H)

[0669] Preparation A2-15: (S)-1-(6-chloro-[3,3'-bipyridin]-4-yl)piperidin-3-ol

[0670] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 3-pyridylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.81 (s, 1H), 8.70-8.68 (m, 1H), 8.06 (s, 1H), 7.88-7.87 (m, 1H), 7.45-7.42 (m, 1H), 6.93 (s, 1H), 3.82-3.75 (m, 1H), 3.21-3.18 (m, 1H), 2.75-2.73 (m, 1H), 2.72-2.70 (m, 2H), 1.72-1.70 (m, 2H), 1.48-1.47 (m, 1H)

[0671] Preparation A2-16: (S)-1-(6-chloro-6'-ethoxy-[3,3'-bipyridin]-4-yl)piperidin-3-ol

[0672] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 6-ethoxypyridin-3-boronic acid. 1H NMR (CDCl3, 400MHz) δ 8.27 (s, 1H), 8.03 (s, 1H), 7.77 (d, 1H), 6.89 (s, 1H), 6.83 (d, 1H), 4.41 (q, 2H), 3.77-3.75 (m, 1H), 3.24-3.22 (m, 1H), 2.98-2.97 (m, 1H), 2.76-2.68 (m, 2H), 1.90-1.87 (m, 1H), 1.74-1.72 (m, 2H), 1.68 (t, 3H)

[0673] Preparation A2-17: (S)-1-(6-chloro-6'-(trifluoromethyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol

[0674] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 2-(trifluoromethyl)pyridin-5-boronic acid. 1H NMR (CDCl3, 400MHz) δ 8.93 (s, 1H), 8.07 (s, 1H), 8.05 (d, 1H), 7.82 (d, 1H), 6.97 (s, 1H), 3.78-3.76 (m, 1H), 3.23-3.22 (m, 1H), 3.20-3.19 (m, 1H), 2.96-2.73 (m, 2H), 1.95-1.92 (m, 1H), 1.91-1.88 (m, 1H), 1.69-1.49 (m, 2H)

[0675] Preparation A2-18: (S)-1-(2-chloro-5-(imidazo[1,2-a]pyridin-6-yl)pyridin-4-yl)piperidin-3-ol

[0676] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to imidazo[1,2-a]pyridin-6-ylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.28 (s, 1H), 8.08 (s, 1H), 7.62-7.59 (m, 1H), 7.52-7.51 (m, 1H), 7.40-7.38 (m, 2H), 6.92 (s, 1H), 3.82-3.78 (m, 1H), 3.34-3.20 (m, 1H), 3.05-2.92 (m, 1H), 2.81-2.73 (m, 2H), 2.12-2.05 (m, 1H), 1.91-1.84 (m, 1H), 1.49-1.47 (m, 2H)

[0677] Preparation A2-19: (S)-1-(5-([1,2,4]triazolo[4,3-a]pyridin-6-yl)-2-chloropyridin-4-yl)piperidin-3-ol

[0678] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to [1,2,4]triazolo[4,3-a]pyridin-6-ylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.80 (s, 1H), 8.30 (s, 1H), 8.08 (s, 1H), 7.79 (d, 1H), 7.54 (d, 1H), 6.95 (s, 1H), 3.92-3.81 (m, 1H), 3.33-3.30 (m, 1H), 3.12-3.10 (m, 1H), 2.90-2.88 (m, 1H), 2.79-2.74 (m, 1H), 1.96-1.93 (m, 1H), 1.82-1.73 (m, 1H), 1.51-1.48 (m, 2H)

[0679] Preparation A2-20: (3S)-1-[2-chloro-5-[1-(2,2,6,6-tetramethyltetrahydropyran-4-yl)pyrazol-4-yl]-4-pyridyl]piperidin-3-ol

[0680] The titled compound was prepared in accordance with the same procedures as in Preparation A2-1, changing the boronic acid reagent to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,6,6-tetramethyltetrahydropyran-4-yl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 7.82 (s, 1H), 7.77 (s, 1H), 6.90 (s, 1H), 4.80-4.70 (m, 1H), 3.95-3.85 (m, 1H), 3.70-3.65 (m, 1H), 3.30-3.20 (m, 1H), 3.10-3.00 (m, 1H), 2.80-2.65 (m, 2H), 2.20-2.10 (m, 2H), 2.00-1.90 (m, 1H), 1.90-1.80 (m, 2H), 1.70-1.60 (m, 1H), 1.60-1.50 (m, 1H), 1.42 (s, 6H), 1.34 (s, 6H)

[0681] Preparation A3-1: tert-butyl (S)-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0682] Step 1: tert-butyl (S)-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)carbamate (A3)

[0683] 2-Chloro-4-fluoro-5-iodopyridine (5.0 g, 19.42 mmol) was dissolved in anhydrous dimethylformamide (90.6 mL) and then (S)-3-(tert-butoxycarbonylamino)piperidine (4.28 g, 21.36 mmol) and diisopropylethylamine (7.9mL, 58.26mmol) were added dropwise thereto. The reaction mixture was stirred at 50℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (5.9 g). (Yield: 69.9%) 1H NMR (CDCl3, 400MHz) δ 8.57 (s, 1H), 6.85 (s, 1H), 4.92 (brs, 1H), 3.95-3.94 (m, 1H), 3.34 (d, 1H), 3.08-3.04 (m, 2H), 2.90-2.85 (m, 1H), 2.06-1.94 (m, 3H), 1.46 (s, 9H)

[0684] Step 2: tert-butyl (S)-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate (A3-1)

[0685] tert-Butyl (S)-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)carbamate (3.0 g, 6.85 mmol) was dissolved in anhydrous 1,4-dioxane (34.3 mL) and then 1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-boronic acid pinacol ester (2.9 g, 10.28 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (559.7 mg, 0.68 mmol), and 2.0M sodium carbonate solution (12.1 mL, 24.2 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 100℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (2.3 g). (Yield: 73.0%) 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.81 (s, 1H), 7.77 (s, 1H), 6.86 (s, 1H), 4.55-4.45 (m, 1H), 4.45-4.35 (m, 1H), 4.20-4.10 (m, 2H), 3.80-3.70 (m, 1H), 3.61 (t, 2H), 3.50-3.40 (m, 1H), 3.15-3.00 (m, 1H), 2.65-2.55 (m, 1H), 2.55-2.45 (m, 1H), 2.25-2.05 (m, 4H), 2.00-1.90 (m, 1H), 1.75-1.65 (m, 1H), 1.45 (s, 9H), 1.40-1.30 (m, 1H)

[0686] Preparation A3-2: tert-butyl (S)-(1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0687] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.13 (d, 2H), 7.94 (s, 1H), 7.26 (t, 1H), 6.90 (s, 1H), 4.48-4.47 (m, 1H), 3.76-3.67 (m, 1H), 3.46-3.43 (m, 1H), 3.08-3.05 (m, 1H), 2.62-2.52 (m, 2H), 1.98-1.96 (m, 1H), 1.73-1.64 (m, 1H), 1.45 (s, 9H), 1.38-1.31 (m, 2H)

[0688] Preparation A3-3: tert-butyl (S)-(1-(2-chloro-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0689] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 7.79-7.75 (m, 2H), 6.85 (s, 1H), 4.57-4.48 (m, 1H), 4.23-4.16 (m, 1H), 3.76-3.70 (m, 1H), 3.42 (d, 1H), 3.07-3.03 (m, 3H), 2.58-2.55 (m, 2H), 2.36 (s, 3H), 2.23-2.12 (m, 7H), 1.96-1.94 (m, 1H), 1.65-1.54 (m, 2H), 1.43 (s, 9H)

[0690] Preparation A3-4: tert-butyl (S)-(1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0691] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.88 (s, 1H), 7.82 (s, 1H), 6.88 (s, 1H), 4.83-4.78 (m, 2H), 4.50-4.42 (m, 1H), 3.73-3.69 (m, 1H), 3.44-3.41 (m, 1H), 3.11-3.09 (m, 1H), 2.63-2.58 (m, 1H), 2.45-2.43 (m, 1H), 2.00-1.94 (m, 1H), 1.73-1.70 (m, 1H), 1.44 (s, 9H), 1.35-1.28 (m, 1H)

[0692] Preparation A3-5: tert-butyl (S)-(1-(2-chloro-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0693] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-(2-methoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 7.83 (s, 1H), 7.76 (s, 1H), 6.85 (s, 1H), 4.58-4.52 (m, 1H), 4.37-4.35 (m, 2H), 3.81-3.79 (m, 3H), 3.40-3.35 (m, 4H), 3.05-3.02 (m, 1H), 2.61-2.56 (m, 1H), 1.93-1.92 (m, 1H), 1.65-1.63 (m, 1H), 1.46 (s, 9H), 1.41-1.31 (m, 1H)

[0694] Preparation A3-6: tert-butyl (S)-(1-(2-chloro-5-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0695] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-(3-methoxypropyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CD3OD, 400MHz) δ 8.07 (s, 1H), 8.00 (s, 1H), 7.81 (s, 1H), 7.02 (s, 1H), 4.30 (t, 2H), 3.59 (brs, 1H), 3.43-3.32 (m, 3H), 3.32 (s, 3H), 3.22 (d, 1H), 2.62 (t, 1H), 2.51 (t, 1H), 2.17-2.11 (m, 2H), 1.96-1.93 (m, 1H), 1.73 (brs, 1H), 1.70-1.62 (m, 1H), 1.59 (s, 9H), 1.51-1.43 (m, 1H)

[0696] Preparation A3-7: tert-butyl (S)-(1-(2-chloro-5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0697] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-methyl-3-(trifluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CD3OD, 400MHz) δ 7.91 (s, 1H), 7.88 (s, 1H), 7.03 (s, 1H), 4.09 (s, 1H), 3.34-3.32 (m, 2H), 3.27-3.23 (m, 1H), 2.71 (t, 1H), 2.38 (t, 1H), 1.90-1.86 (m, 1H), 1.71 (brs, 1H), 1.60-1.54 (m, 2H), 1.44 (s, 9H)

[0698] Preparation A3-8: tert-butyl (S)-(1-(2-chloro-5-(1-(2-(dimethylamino)-2-oxoethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0699] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to N,N-dimethyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)acetamide. 1H NMR (CD3OD, 400MHz) δ 8.13 (s, 1H), 8.04 (s, 1H), 7.85 (s, 1H), 5.24-5.14(m, 2H), 3.63-3.59 (m, 1H), 3.45-3.41 (m, 2H), 3.17 (s, 3H), 3.01 (s, 3H), 2.65-2.55 (m, 2H), 2.03-1.97 (m, 1H), 1.96-1.92 (m, 1H), 1.74-1.66 (m, 1H), 1.46 (s, 9H), 1.40 (brs, 1H)

[0700] Preparation A3-9: tert-butyl (S)-(1-(2-chloro-5-(1-(2-(methoxymethoxy)ethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0701] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-(2-(methoxymethoxy)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.09 (d, 2H), 7.85 (s, 1H), 7.04 (s, 1H), 4.60 (s, 2H), 4.43-4.42 (m, 2H), 3.94 (t, 2H), 3.63-3.61 (m, 1H), 3.43-3.41 (m, 1H), 3.26 (s, 3H), 3.25 (brs, 1H), 2.62-2.53 (m, 2H), 1.97-1.93 (m, 2H), 1.73-1.69 (m, 2H), 1.45 (s, 9H), 1.39-1.31 (m, 1H)

[0702] Preparation A3-10: tert-butyl (S)-(1-(2-chloro-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0703] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-(2,2-difluoroethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 7.83 (s, 1H), 7.82 (s, 1H), 6.88 (s, 1H), 6.34-6.19 (m, 1H), 4.60-4.53 (m, 2H), 3.82-3.70 (m, 1H), 3.46-3.43 (m, 1H), 3.12-3.09 (m, 1H), 2.64-2.61 (m, 1H), 2.53-2.42 (m, 1H), 1.98-1.92 (m, 1H), 1.83-1.74 (m, 1H), 1.72-1.62 (m, 1H), 1.57 (s, 9H), 1.45-1.43 (m, 1H)

[0704] Preparation A3-11: tert-butyl (S)-(1-(2-chloro-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0705] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(trifluoromethyl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 8.12 (s, 1H), 8.06 (s, 1H), 6.92 (s, 1H), 4.47 (brs, 1H), 3.81-3.71 (m, 1H), 3.49-3.47 (m, 1H), 3.09-3.06 (m, 1H), 2.65-2.53 (m, 2H), 1.99-1.96 (m, 1H), 1.73-1.68 (m, 1H), 1.46 (s, 9H), 1.45-1.37 (m, 2H)

[0706] Preparation A3-12: tert-butyl (S)-(1-(2-chloro-5-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0707] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-[2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]ethyl]morpholine. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 7.81 (s, 1H), 7.77 (s, 1H), 6.87 (s, 1H), 4.55-4.45 (m, 1H), 4.33 (t, 2H), 3.80-3.75 (m, 1H), 3.72 (t, 4H), 3.50-3.40 (m, 1H), 3.15-3.05 (m, 1H), 2.89 (t, 2H), 2.65-2.60 (m, 1H), 2.60-2.45 (m, 5H), 2.00-1.90 (m, 1H), 1.75-1.65 (m, 1H), 1.46 (s, 9H), 1.40-1.30 (m, 1H)

[0708] Preparation A3-13: tert-butyl (S)-(1-(2-chloro-5-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0709] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-(2-pyrrolidin-1-ylethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.80 (s, 1H), 7.74 (s, 1H), 6.84 (s, 1H), 4.60-4.50 (m, 1H), 4.30 (t, 2H), 3.80-3.70 (m, 1H), 3.45-3.35 (m, 1H), 3.10-2.90 (m, 3H), 2.70-2.50 (m, 6H), 2.00-1.90 (m, 1H), 1.85-1.70 (m, 4H), 1.70-1.60 (m, 1H), 1.44 (s, 9H), 1.40-1.30 (m, 1H)

[0710] Preparation A3-14: tert-butyl N-[(3S)-1-[2-chloro-5-[1-(2-cyanoethyl)pyrazol-4-yl]-4-pyridyl]-3-piperidyl]carbamate

[0711] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]propanenitrile. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.86 (s, 1H), 7.83 (s, 1H), 6.89 (s, 1H), 4.50 (t, 2H), 4.50-4.40 (m, 1H), 3.75-3.65 (m, 1H), 3.50-3.40 (m, 1H), 3.20-3.05 (m, 2H), 3.09 (t, 2H), 2.70-2.60 (m, 1H), 2.45-2.35 (m, 1H), 2.05-1.95 (m, 1H), 1.80-1.70 (m, 1H), 1.45 (s, 9H), 1.40-1.30 (m, 1H)

[0712] Preparation A3-15: tert-butyl (S)-3-(3-(4-(3-((tert-butoxycarbonyl)amino)piperidin-1-yl)-6-chloropyridin-3-yl)-1H-pyrazol-1-yl)azetidin-1-carboxylate

[0713] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to tert-butyl 3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)azetidin-1-carboxylate. 1H NMR (CDCl3, 400MHz) δ 8.31 (s, 1H), 7.65 (s, 1H), 6.86 (s, 1H), 6.60 (s, 1H), 5.25-5.15 (m, 1H), 5.75-5.65 (m, 1H), 4.43 (t, 2H), 4.40-4.20 (m, 2H), 3.75-3.65 (m, 1H), 3.30-3.20 (m, 1H), 3.10-3.00 (m, 1H), 2.80-2.70 (m, 1H), 2.65-2.55 (m, 1H), 1.90-1.80 (m, 1H), 1.80-1.65 (m, 1H), 1.47 (s, 9H), 1.44 (s, 9H), 1.40-1.30 (m, 1H)

[0714] Preparation A3-16: tert-butyl (S)-(1-(6-chloro-6'-(dimethylamino)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0715] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 6-dimethylaminopyridin-3-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.23 (d, 1H), 8.00 (s, 1H), 7.65 (d, 1H), 6.84 (s, 1H), 6.59 (d, 1H), 4.55-4.45 (m, 1H), 3.80-3.65 (m, 1H), 3.40-3.30 (m, 1H), 3.15 (s, 6H), 3.10-3.00 (m, 1H), 2.70-2.55 (m, 2H), 1.90-1.80 (m, 1H), 1.60-1.48 (m, 1H), 1.45 (s, 9H), 1.35-1.30 (m, 1H)

[0716] Preparation A3-17: tert-butyl (S)-(1-(6-chloro-6'-(pyrrolidin-1-yl)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0717] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 2-pyrrolidin-1-yl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine. 1H NMR (CDCl3, 400MHz) δ 8.22 (d, 1H), 8.00 (s, 1H), 7.64 (d, 1H), 6.84 (s, 1H), 6.44 (d, 1H), 4.55-4.45 (m, 1H), 3.80-3.65 (m, 1H), 3.51 (t, 4H), 3.40-3.30 (m, 1H), 3.10-3.00 (m, 1H), 2.70-2.55 (m, 2H), 2.05 (t, 4H), 1.90-1.80 (m, 1H), 1.60-1.48 (m, 1H), 1.45 (s, 9H), 1.35-1.30 (m, 1H)

[0718] Preparation A3-18: tert-butyl (S)-(1-(6-chloro-6'-(piperidin-1-yl)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0719] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 6-(piperidin-1-yl)pyridin-3-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.23 (d, 1H), 8.00 (s, 1H), 7.65 (d, 1H), 6.85 (s, 1H), 6.72 (d, 1H), 4.55-4.45 (m, 1H), 3.80-3.65 (m, 1H), 4.65-4.55 (m, 4H), 3.45-3.30 (m, 3H), 3.10-3.00 (m, 1H), 2.70-2.55 (m, 2H), 2.05 (t, 4H), 1.70-1.50 (m, 5H), 1.60-1.48 (m, 1H), 1.46 (s, 9H), 1.35-1.30 (m, 1H)

[0720] Preparation A3-19: tert-butyl (S)-(1-(6-chloro-6'-morpholino-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0721] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 6-(morpholin-4-yl)pyridin-3-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.28 (d, 1H), 8.00 (s, 1H), 7.71 (d, 1H), 6.86 (s, 1H), 6.72 (d, 1H), 4.55-4.45 (m, 1H), 3.87-3.83 (m, 4H), 3.80-3.65 (m, 1H), 3.59-3.54 (m, 4H), 3.40-3.30 (m, 1H), 3.10-3.00 (m, 1H), 2.70-2.50 (m, 2H), 1.95-1.80 (m, 1H), 1.60-1.50 (m, 1H), 1.45 (s, 9H), 1.35-1.30 (m, 1H)

[0722] Preparation A3-20: tert-butyl (S)-(1-(2-chloro-5-(4-(4-methylpiperazin-1-carbonyl)phenyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0723] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to (4-methylpiperazin-1-yl)-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanone. 1H NMR (CD3OD, 400MHz) δ 7.96 (s, 1H), 7.65 (dd, 2H), 7.56 (dd, 2H), 7.07 (s, 1H), 3.90-3.75 (m, 2H), 3.70-3.50 (m, 2H), 3.50-3.40 (m, 2H), 3.40-3.35 (m, 1H), 3.20-3.10 (m, 1H), 2.75-2.60 (m, 2H), 2.60-2.40 (m, 4H), 2.36 (s, 3H), 1.95-1.85 (m, 1H), 1.65-1.55 (m, 1H), 1.45 (s, 9H), 1.40-1.30 (m, 1H)

[0724] Preparation A3-21: tert-butyl (S)-(1-(2-chloro-5-(1-(2-methoxy-2-methylpropyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl) carbamate

[0725] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-(2-methoxy-2-methyl-propyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CD3OD, 400MHz) δ 8.18 (s, 1H), 7.84 (s, 1H), 7.76 (s, 1H), 6.91 (s, 1H), 4.66-4.54 (m, 1H), 4.25-4.15 (m, 2H), 3.88-3.76 (m, 1H), 3.75-3.65 (m, 1H), 3.44-3.35 (m, 1H), 3.31 (s, 3H), 3.09-2.98 (m, 1H), 2.71-2.58 (m, 2H), 1.98-1.86 (m, 1H), 1.71-1.52 (m, 1H), 1.51 (s, 9H), 1.43-1.33 (m, 1H), 1.23 (s, 6H)

[0726] Preparation A3-22: tert-butyl (S)-(1-(6-chloro-6'-(2-methoxyethoxy)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0727] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 2-(2-methoxyethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine. 1H NMR (CD3OD, 400MHz) δ 8.26 (s, 1H), 8.06 (s, 1H), 7.82-7.74 (m, 1H), 6.91-6.86 (m, 2H), 4.57-4.52 (m, 2H), 4.52-4.45 (m, 1H), 3.85-3.78 (m, 2H), 3.78-3.63 (m, 2H), 3.52-3.45 (m, 3H), 3.42-3.33 (m, 1H), 3.06-2.94 (m, 1H), 2.73-2.52 (m, 2H), 1.94-1.82 (m, 1H), 1.51 (s, 9H)

[0728] Preparation A3-23: tert-butyl (S)-(1-(2-chloro-5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl) carbamate

[0729] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to [1-(2-hydroxy-2-methyl-propyl)pyrazol-4-yl]boronic acid pinacol ester. 1H NMR (CD3OD, 400MHz) δ 8.24 (s, 1H), 7.99 (s, 1H), 7.84 (s, 1H), 6.94 (s, 1H), 4.48-4.38 (m, 1H), 4.23-4.16 (m, 1H), 4.16 (s, 2H), 3.80-3.63 (m, 1H), 3.62-3.48 (m, 1H), 3.24-3.06 (m, 1H), 2.75-2.62 (m, 1H), 2.29-2.14 (m, 1H), 2.07-1.96 (m, 1H), 1.87-1.77 (m, 1H), 1.77-1.62 (m, 1H), 1.49 (s, 9H)

[0730] Preparation A3-24: tert-butyl (S)-(1-(2-chloro-5-(1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0731] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to N,N-dimethyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]propan-1-amine. 1H NMR (CD3OD, 400MHz) δ 8.18 (s, 1H), 7.84 (s, 2H), 6.91 (s, 1H), 4.57-4.46 (m, 1H), 4.34 (t, 2H), 3.82-3.67 (m, 1H), 3.47-3.36 (m, 1H), 3.15-3.05 (m, 1H), 2.63-2.57 (m, 2H), 2.57-2.51 (m, 1H), 2.47 (s, 6H), 2.32-2.21 (m, 2H), 2.03-1.91 (m, 1H), 1.78-1.68 (m, 1H), 1.67-1.54 (m, 1H), 1.51 (s, 9H)

[0732] Preparation A3-25: tert-butyl (S)-3-((4-(4-(3-((tert-butoxycarbonyl)amino)piperidin-1-yl)-6-chloropyridin-3-yl)-1H-pyrazol-1-yl)methyl)azetidin-1-carboxylate

[0733] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to tert-butyl 3-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]methyl]azetidin-1-carboxylate. 1H NMR (CD3OD, 400MHz) δ 8.17 (s, 1H), 7.81 (s, 1H), 7.76 (s, 1H), 6.91 (s, 1H), 4.55-4.45 (m, 1H), 4.45 (d, 2H), 4.15-4.03 (m, 2H), 3.85-3.76 (m, 2H), 3.76-3.66 (m, 1H), 3.52-3.36 (m, 1H), 3.20-3.02 (m, 2H), 2.67-2.54 (m, 1H), 2.54-2.40 (m, 1H), 2.03-1.89 (m, 1H), 1.78-1.67 (m, 1H), 1.65-1.52 (m, 1H), 1.51 (s, 18H)

[0734] Preparation A3-26: tert-butyl (R)-3-(4-(4-((S)-3-((tert-butoxycarbonyl)amino)piperidin-1-yl)-6-chloropyridin-3-yl)-1H-pyrazol-1-yl)pyrrolidin-1-carboxylate

[0735] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to tert-butyl (R)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)pyrrolidin-1-carboxylate. 1H NMR (CD3OD, 400MHz) δ 8.18 (s, 1H), 7.83-7.74 (m, 2H), 6.91 (s, 1H), 5.02-4.90 (m, 1H), 4.55-4.42 (m, 1H), 3.93-3.88 (m, 1H), 3.86-3.77 (m, 1H), 3.77-3.62 (m, 2H), 3.62-3.52 (m, 1H), 3.52-3.41 (m, 1H), 3.16-3.04 (m, 1H), 2.68-2.55 (m, 1H), 2.56-2.39 (m, 3H), 2.04-1.91 (m, 1H), 1.79-1.66 (m, 1H), 1.52 (s, 9H), 1.47 (s, 9H)

[0736] Preparation A3-27: tert-butyl (S)-3-(4-(4-((S)-3-((tert-butoxycarbonyl)amino)piperidin-1-yl)-6-chloropyridin-3-yl)-1H-pyrazol-1-yl)pyrrolidin-1-carboxylate

[0737] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to tert-butyl (S)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)pyrrolidin-1-carboxylate. 1H NMR (CD3OD, 400MHz) δ 8.18 (s, 1H), 7.85-7.72 (m, 2H), 6.92 (s, 1H), 5.02-4.91 (m, 1H), 4.56-4.43 (m, 1H), 3.99-3.89 (m, 1H), 3.89-3.77 (m, 1H), 3.77-3.65 (m, 2H), 3.65-3.52 (m, 2H), 3.52-3.39 (m, 1H), 3.17-3.03 (m, 1H), 2.69-2.54 (m, 1H), 2.52-2.38 (m, 3H), 2.02-1.90 (m, 1H), 1.78-1.67 (m, 1H), 1.52 (s, 9H), 1.49 (s, 9H)

[0738] Preparation A3-28: tert-butyl (S)-(1-(6-chloro-6'-((2-(dimethylamino)ethyl)amino)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0739] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to N',N'-dimethyl-N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]ethan-1,2-diamine. 1H NMR (CD3OD, 400MHz) δ 8.21 (s, 1H), 8.04 (s, 1H), 7.67 (d, 1H), 6.90 (s, 1H), 6.55 (d, 1H), 5.33-5.18 (m, 1H), 4.64-4.51 (m, 1H), 3.80-3.64 (m, 1H), 3.48-3.38 (m, 2H), 3.38-3.30 (m, 1H), 3.08-2.98 (m, 1H), 2.36 (s, 6H), 1.91-1.85 (m, 1H), 1.52 (s, 9H)

[0740] Preparation A3-29: tert-butyl (S)-4-(4'-(3-((tert-butoxycarbonyl)amino)piperidin-1-yl)-6'-chloro-[3,3'-bipyridin]-6-yl)piperazin-1-carboxylate

[0741] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to tert-butyl 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]piperazin-1-carboxylate. 1H NMR (CD3OD, 400MHz) δ 8.30 (s, 1H), 8.04 (s, 1H), 7.76 (d, 1H), 6.91 (s, 1H), 6.74 (d, 1H), 4.54-4.42 (m, 1H), 3.79-3.66 (m, 2H), 3.65-3.51 (m, 8H), 3.43-3.33 (m, 3H), 3.11-3.02 (m, 1H), 2.68-2.52 (m, 2H), 1.49 (s, 9H), 1.30 (s, 9H)

[0742] Preparation A3-30: tert-butyl (S)-(1-(2-chloro-5-(1-(1-methoxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0743] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-(2-methoxy-1,1-dimethyl-ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CD3OD, 400MHz) δ 8.19 (s, 1H), 7.95 (s, 1H), 7.80 (s, 1H), 6.87 (s, 1H), 4.67-4.54 (m, 1H), 3.87-3.77 (m, 1H), 3.77-3.68 (m, 1H), 3.68 (s, 2H), 3.43-3.35 (m, 1H), 3.34 (s, 3H), 3.04-2.93 (m, 1H), 2.71-2.60 (m, 2H), 2.05-1.97 (m, 1H), 1.84-1.76 (m, 1H), 1.69 (s, 6H), 1.52 (s, 9H)

[0744] Preparation A3-31: tert-butyl (S)-(1-(2-chloro-5-(1-((3,3-difluorocyclobutyl)methyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0745] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-[(3,3-difluorocyclobutyl)methyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CD3OD, 400MHz) δ 8.17 (s, 1H), 7.82 (s, 1H), 7.76 (s, 1H), 6.92 (s, 1H), 4.55-4.45 (m, 1H), 4.35 (d, 2H), 3.81-3.70 (m, 2H), 3.18-3.07 (m, 1H), 2.83-2.70 (m, 3H), 2.66-2.55 (m, 1H), 2.54-2.39 (m, 3H), 2.04-1.95 (m, 1H), 1.75-1.66 (m, 1H), 1.50 (s, 9H)

[0746] Preparation A3-32: tert-butyl (S)-(1-(2-chloro-5-(1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0747] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-ethanamine. 1H NMR (CD3OD, 400MHz) δ 8.19 (s, 1H), 7.87 (s, 1H), 7.79 (s, 1H), 6.91 (s, 1H), 4.66-4.51 (m, 1H), 4.37 (t, 2H), 3.88-3.70 (m, 1H), 3.47-3.32 (m, 1H), 3.09-2.98 (m, 1H), 2.88-2.76 (m, 2H), 2.72-2.57 (m, 2H), 2.37 (s, 6H), 2.00-1.87 (m, 1H), 1.77-1.65 (m, 1H), 1.52 (s, 9H), 1.43-1.37 (m, 1H)

[0748] Preparation A3-33: tert-butyl (S)-(1-(2-chloro-5-(1-(fluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0749] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-(fluoromethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CD3OD, 400MHz) δ 8.20 (s, 1H), 8.02 (s, 1H), 7.95 (s, 1H), 6.93 (s, 1H), 6.22 (s, 1H), 6.09 (s, 1H), 4.54-4.42 (m, 1H), 3.80-3.66 (m, 2H), 3.50-3.40 (m, 1H), 3.19-3.05 (m, 1H), 2.70-2.56 (m, 1H), 2.55-2.42 (m, 1H), 2.03-1.87 (m, 1H), 1.77-1.67 (m, 1H), 1.52 (s, 9H)

[0750] Preparation A3-34: tert-butyl (S)-4-(4'-(3-((tert-butoxycarbonyl)amino)piperidin-1-yl)-6'-chloro-[3,3'-bipyridin]-6-yl)piperidin-1-carboxylate

[0751] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to tert-butyl 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]piperidin-1-carboxylate. 1H NMR (CD3OD, 400MHz) δ 8.70 (s, 1H), 8.09 (s, 1H), 7.86 (d, 1H), 7.28 (d, 1H), 6.95 (s, 1H), 4.49-4.37 (m, 1H), 4.37-4.21 (m, 2H), 3.72-3.55 (m, 1H), 3.43-3.32 (m, 1H), 3.06-2.95 (m, 1H), 2.95-2.79 (m, 3H), 2.67-2.59 (m, 1H), 2.59-2.47 (m, 1H), 2.05-1.94 (m, 2H), 1.94-1.85 (m, 1H), 1.85-1.71 (m, 2H), 1.53 (s, 9H), 1.47 (s, 9H)

[0752] Preparation A3-35: tert-butyl (S)-(1-(6-chloro-6'-(2-(dimethylamino)ethoxy)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0753] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to N,N-dimethyl-2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]oxyethanamine. 1H NMR (CD3OD, 400MHz) δ 8.26 (s, 1H), 8.06 (s, 1H), 7.80-7.72 (m, 1H), 6.94-6.83 (m, 2H), 4.56 (t, 2H), 3.75-3.62 (m, 1H), 3.40-3.29 (m, 1H), 3.04-2.96 (m, 1H), 2.83 (t, 2H), 2.43 (s, 6H), 1.92-1.83 (m, 1H), 1.80-1.63 (m, 3H), 1.63-1.52 (m, 1H), 1.52 (s, 9H)

[0754] Preparation A3-36: tert-butyl (S)-(1-(6-chloro-6'-(3-ethylureido)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0755] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-ethyl-3-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]urea. 1H NMR (CD3OD, 400MHz) δ 9.32 (s, 1H), 8.33 (s, 1H), 8.07 (s, 1H), 7.84 (d, 1H), 6.95 (s, 1H), 4.52-4.39 (m, 1H), 3.76-3.60 (m, 1H), 3.53 (q, 2H), 3.45-3.37 (m, 1H), 3.12-2.96 (m, 1H), 2.66-2.51 (m, 2H), 2.00-1.86 (m, 1H), 1.64-1.57 (m, 2H), 1.54 (s, 9H), 0.92 (t, 3H)

[0756] Preparation A3-37: tert-butyl N-[(3S)-1-[2-chloro-5-[4-(morpholin-4-carbonyl)phenyl]-4-pyridyl]-3-piperidyl]carbamate

[0757] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-(morpholin-4-carbonyl)phenyl boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.59-7.56 (m, 2H), 7.54-7.51 (m, 2H), 6.91 (s, 1H), 3.90-3.55 (m, 10H), 3.45-3.35 (m, 1H), 3.05-2.95 (m, 1H), 2.65-2.55 (m, 2H), 1.95-1.85 (m, 1H), 1.46 (s, 9H), 1.46-1.40 (m, 2H)

[0758] Preparation A3-38: tert-butyl N-[(3S)-1-[2-chloro-5-(4-methyl-2,3-dihydropyrido[3,2-b][1,4]oxazin-7-yl)-4-pyridyl]-3-piperidyl]carbamate

[0759] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydropyrido[3,2-b][1,4]oxazine. 1H NMR (CDCl3, 400MHz) δ 8.02 (s, 1H), 7.83 (s, 1H), 7.14 (s, 1H), 6.84 (s, 1H), 4.55-4.40 (m, 1H), 4.40-4.25 (m, 2H), 3.75-3.65 (m, 1H), 3.55-3.45 (m, 2H), 3.41 (d, 1H), 3.19 (s, 3H), 3.15-3.05 (m, 1H), 2.70-2.50 (m, 2H), 1.95-1.85 (m, 1H), 1.55-1.48 (m, 1H), 1.46 (s, 9H), 1.35-1.25 (m, 1H)

[0760] Preparation A3-39: tert-butyl N-[(3S)-1-[2-chloro-5-(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)-4-pyridyl]-3-piperidyl]carbamate

[0761] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazine. 1H NMR (CDCl3, 400MHz) δ 8.02 (s, 1H), 6.97 (d, 1H), 6.92 (s, 1H), 6.82 (s, 1H), 6.72 (d, 1H), 4.60-4.50 (m, 1H), 4.40-4.30 (m, 2H), 3.80-3.70 (m, 1H), 3.40-3.25 (m, 3H), 3.05-2.96 (m, 1H), 2.95 (s, 3H), 2.70-2.60 (m, 2H), 1.90-1.80 (m, 1H), 1.55-1.40 (m, 10H), 1.40-1.35 (m, 1H)

[0762] Preparation A3-40: tert-butyl N-[(3S)-1-[2-chloro-5-(2-oxo-1,4-dihydro-3,1-benzoxazin-6-yl)-4-pyridyl]-3-piperidyl]carbamate

[0763] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one. 1H NMR (CDCl3, 400MHz) δ 8.00 (s, 1H), 7.41 (d, 1H), 7.13 (s, 1H), 6.90-6.85 (m, 1H), 6.67 (d, 1H), 5.45-5.35 (m, 2H), 4.45-4.35 (m, 1H), 3.70-3.60 (m, 1H), 3.35-3.30 (m, 1H), 3.10-3.00 (m, 1H), 2.64 (t, 1H), 2.51 (t, 1H), 1.95-1.85 (m, 1H), 1.45 (s, 9H), 1.45-1.35 (m, 1H), 1.35-1.30 (m, 1H)

[0764] Preparation A3-41: tert-butyl N-[(3S)-1-[2-chloro-5-[4-(2-oxopyrrolidin-1-yl)phenyl]-4-pyridyl]-3-piperidyl]carbamate

[0765] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-(2-oxo-1-pyrrolidinyl)phenyl boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.75 (d, 2H), 7.50 (d, 2H), 6.87 (s, 1H), 4.55-4.45 (m, 1H), 3.95 (t, 2H), 3.75-3.65 (m, 1H), 3.35-3.25 (m, 1H), 3.05-2.95 (m, 1H), 2.70-2.60 (m, 3H), 2.30-2.10 (m, 3H), 1.90-1.80 (m, 1H), 1.46 (s, 9H), 1.46-1.30 (m, 2H)

[0766] Preparation A3-42: tert-butyl N-[(3S)-1-[2-chloro-5-(3-oxo-4H-1,4-benzoxazin-7-yl)-4-pyridyl]-3-piperidyl]carbamate

[0767] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one. 1H NMR (CDCl3, 400MHz) δ 8.02 (s, 1H), 7.68 (s, 1H), 7.16 (s, 1H), 7.10-7.05 (m, 1H), 6.90-6.80 (m, 2H), 4.73 (q, 2H), 4.45-4.35 (m, 1H), 3.70-3.60 (m, 1H), 3.40-3.30 (m, 1H), 3.15-3.05 (m, 1H), 2.65 (t, 1H), 2.47 (t, 1H), 1.95-1.85 (m, 1H), 1.70-1.60 (m, 1H), 1.44 (s, 9H), 1.35-1.30 (m, 1H)

[0768] Preparation A3-43: tert-butyl N-[(3S)-1-[2-chloro-5-(4-methyl-3-oxo-1,4-benzoxazin-7-yl)-4-pyridyl]-3-piperidyl]carbamate

[0769] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.20-7.15 (m, 2H), 7.10-7.05 (m, 1H), 6.86 (s, 1H), 4.72 (q, 2H), 4.45-4.35 (m, 1H), 3.70-3.60 (m, 1H), 3.43 (s, 3H), 3.40-3.30 (m, 1H), 3.15-3.05 (m, 1H), 2.65 (t, 1H), 2.47 (t, 1H), 1.95-1.85 (m, 1H), 1.70-1.60 (m, 1H), 1.42 (s, 9H), 1.30-1.20 (m, 1H)

[0770] Preparation A3-44: tert-butyl (S)-(1-(2-chloro-5-(8-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0771] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 8-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one. 1H NMR (CDCl3, 400MHz) δ 7.99 (s, 1H), 7.15 (s, 1H), 6.83 (s, 1H), 6.54 (s, 1H), 4.55-4.45 (m, 1H), 3.75-3.60 (m, 1H), 3.35-3.25 (m, 1H), 3.10-2.95 (m, 3H), 2.90 (t, 1H), 2.80-2.50 (m, 3H), 2.28 (s, 3H), 1.90-1.80 (m, 1H), 1.50-1.40 (m, 10H), 1.40-1.30 (m, 1H)

[0772] Preparation A3-45: tert-butyl (S)-(1-(2-chloro-5-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0773] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one. 1H NMR (CDCl3, 400MHz) δ 8.01 (s, 1H), 7.30 (s, 1H), 6.90-6.80 (m, 2H), 6.80-6.70 (m, 1H), 4.50-4.40 (m, 1H), 3.70-3.60 (m, 1H), 3.40 (s, 3H), 3.35-3.30 (m, 1H), 3.10-2.95 (m, 3H), 2.85 (t, 1H), 2.80-2.60 (m, 3H), 1.90-1.80 (m, 1H), 1.50-1.40 (m, 10H), 1.40-1.30 (m, 1H)

[0774] Preparation A3-46: tert-butyl 4-[4-[6-chloro-4-[(3S)-3-(tert-butoxycarbonylamino)-1-piperidyl]-3-pyridyl]benzoyl]piperazin-1-carboxylate

[0775] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl]piperazin-1-carboxylate. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.60-7.55 (m, 2H), 7.55-7.50 (m, 2H), 6.90 (s, 1H), 4.55-4.45 (m, 1H), 3.75-3.60 (m, 4H), 3.60-3.40 (m, 5H), 3.05-2.95 (m, 1H), 2.70-2.50 (m, 2H), 1.95-1.85 (m, 1H), 1.55-1.45 (m, 10H), 1.45-1.40 (m, 2H)

[0776] Preparation A3-47: tert-butyl N-[(3S)-1-[2-chloro-5-[1-(2,2,6,6-tetramethyltetrahydropyran-4-yl)pyrazol-4-yl]-4-pyridyl]-3-piperidyl]carbamate

[0777] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,6,6-tetramethyltetrahydropyran-4-yl)pyrazole. 1H NMR (MeOD, 400MHz) δ 8.13 (s, 1H), 8.09 (s, 1H), 7.84 (s, 1H), 7.03 (s, 1H), 4.90-4.80 (m, 1H), 3.65-3.50 (m, 1H), 3.50-3.40 (m, 1H), 3.30-3.20 (m, 1H), 2.64 (t, 1H), 2.41 (t, 1H), 2.25-2.10 (m, 2H), 2.00-1.85 (m, 2H), 1.85-1.70 (m, 1H), 1.70-1.55 (m, 1H), 1.50-1.35 (m, 15H), 1.31 (s, 6H), 1.25-1.15 (m, 2H)

[0778] Preparation A3-48: tert-butyl N-[(3S)-1-[2-chloro-5-(2-methyl-3-oxo-4H-1,4-benzoxazin-6-yl)-4-pyridyl]-3-piperidyl]carbamate

[0779] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 3,4-dihydro-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2H-1,4-benzoxazine. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.15-7.05 (m, 2H), 7.05-6.95 (m, 1H), 6.87 (s, 1H), 3.75-3.60 (m, 1H), 3.35-3.25 (m, 1H), 3.05-2.90 (m, 1H), 2.70-2.50 (m, 2H), 1.90-1.80 (m, 1H), 1.70-1.65 (m, 1H), 1.61 (s, 3H), 1.60-1.50 (m, 2H), 1.46 (s, 9H)

[0780] Preparation A3-49: tert-butyl N-[(3S)-1-[2-chloro-5-(4-methyl-3-oxo-pyrido[3,2-b][1,4]oxazin-7-yl)-4-pyridyl]-3-piperidyl]carbamate

[0781] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrido[3,2-b][1,4]oxazin-3-one. 1H NMR (CDCl3, 400MHz) δ 8.05-8.00 (m, 2H), 6.88 (s, 1H), 6.69 (s, 1H), 4.95-4.85 (m, 1H), 4.80-4.70 (m, 1H), 4.35-4.25 (m, 1H), 3.53 (s, 3H), 3.25-3.05 (m, 3H), 2.70-2.60 (m, 1H), 2.30-2.20 (m, 1H), 2.00-1.90 (m, 1H), 1.85-1.75 (m, 1H), 1.75-1.65 (m, 1H), 1.60-1.50 (m, 1H), 1.48 (s, 9H)

[0782] Preparation A3-50: tert-butyl N-[(3S)-1-[2-chloro-5-(3-oxo-4H-pyrido[3,2-b][1,4]oxazin-7-yl)-4-pyridyl]-3-piperidyl]carbamate

[0783] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4H-pyrido[3,2-b][1,4]oxazin-3-one. 1H NMR (CDCl3, 400MHz) δ 9.41 (s, 1H), 8.15-8.05 (m, 2H), 7.48 (s, 1H), 6.89 (s, 1H), 4.95-4.85 (m, 1H), 4.80-4.70 (m, 1H), 4.40-4.30 (m, 1H), 3.60-3.50 (m, 1H), 3.45-3.30 (m, 1H), 3.25-3.15 (m, 1H), 2.67 (t, 1H), 2.29 (t, 1H), 2.00-1.90 (m, 1H), 1.85-1.70 (m, 1H), 1.70-1.60 (m, 1H), 1.38 (s, 9H)

[0784] Preparation A3-51: tert-butyl N-[(3S)-1-[2-chloro-5-(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-3-yl)-4-pyridyl]-3-piperidyl]carbamate

[0785] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-1H-1,8-naphthyridin-2-one. 1H NMR (CDCl3, 400MHz) δ 8.27 (s, 1H), 8.20 (s, 1H), 8.04 (s, 1H), 7.70 (s, 1H), 6.90 (s, 1H), 4.45-4.35 (m, 1H), 3.60-3.50 (m, 1H), 3.45-3.35 (m, 1H), 3.20-3.10 (m, 1H), 3.10-3.00 (m, 2H), 2.90-2.70 (m, 2H), 2.67 (t, 1H), 2.40 (t, 1H), 2.00-1.90 (m, 1H), 1.75-1.65 (m, 1H), 1.60-1.50 (m, 1H), 1.42 (s, 9H)

[0786] Preparation A3-52: tert-butyl N-[(3S)-1-[2-chloro-5-[1-(oxetan-3-yl)pyrazol-4-yl]-4-pyridyl]-3-piperidyl]carbamate

[0787] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-(oxetan-3-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.16 (s, 1H), 7.93 (s, 1H), 7.88 (s, 1H), 6.89 (s, 1H), 5.60-5.50 (m, 1H), 5.20-5.05 (m, 4H), 4.50-4.40 (m, 1H), 3.75-3.65 (m, 1H), 3.50-3.40 (m, 1H), 3.20-3.10 (m, 1H), 2.65 (t, 1H), 2.39 (t, 1H), 2.00-1.90 (m, 1H), 1.80-1.70 (m, 1H), 1.70-1.60 (m, 1H), 1.44 (s, 9H)

[0788] Preparation A3-53: methyl 2-[4-[6-chloro-4-[(3S)-3-(tert-butoxycarbonylamino)-1-piperidyl]-3-pyridyl]pyrazol-1-yl]-2-methyl-propanoate

[0789] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to methyl 2-methyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]propanoate. 1H NMR (CDCl3, 400MHz) δ 8.16 (s, 1H), 7.93 (s, 1H), 7.81 (s, 1H), 6.87 (s, 1H), 4.65-4.55 (m, 1H), 3.75 (s, 3H), 3.45-3.35 (m, 1H), 3.10-3.00 (m, 1H), 2.70-2.55 (m, 2H), 2.00-1.90 (m, 6H), 1.70-1.60 (m, 1H), 1.60-1.50 (m, 1H), 1.46 (s, 9H), 1.46-1.25 (m, 2H)

[0790] Preparation A3-54: tert-butyl N-[(3S)-1-[5-(4-acetamidophenyl)-2-chloro-4-pyridyl]-3-piperidyl]carbamate

[0791] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-acetamidobenzeneboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.65-7.60 (m, 2H), 7.50-7.40 (m, 2H), 7.24 (s, 1H), 6.87 (s, 1H), 4.65-4.55 (m, 1H), 3.75-3.65 (m, 1H), 3.35-3.25 (m, 1H), 3.00-2.90 (m, 1H), 2.70-2.55 (m, 2H), 2.23 (s, 3H), 1.90-1.80 (m, 1H), 1.47 (s, 9H), 1.45-1.30 (m, 2H)

[0792] Preparation A3-55: tert-butyl N-[(3S)-1-[2-chloro-5-[3-(dimethylcarbamoyl)phenyl]-4-pyridyl]-3-piperidyl]carbamate

[0793] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 3-(dimethylcarbamoyl)phenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.06 (s, 1H), 7.67 (s, 1H), 7.60-7.45 (m, 2H), 7.45-7.35 (m, 1H), 6.89 (s, 1H), 4.95-4.85 (m, 1H), 3.80-3.70 (m, 1H), 3.35-3.25 (m, 1H), 3.15 (s, 3H), 3.13 (s, 3H), 2.90-2.80 (m, 1H), 2.80-2.70 (m, 1H), 2.70-2.60 (m, 1H), 1.85-1.75 (m, 1H), 1.50-1.30 (m, 11H)

[0794] Preparation A3-56: tert-butyl N-[(3S)-1-[2-chloro-5-[3-methyl-4-(trifluoromethoxy)phenyl]-4-pyridyl]-3-piperidyl]carbamate

[0795] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 3-methyl-4-trifluoromethoxyphenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.39 (s, 1H), 7.35-7.30 (m, 2H), 6.88 (s, 1H), 4.55-4.45 (m, 1H), 3.80-3.65 (m, 1H), 3.35-3.25 (m, 1H), 2.95-2.85 (m, 1H), 2.70-2.60 (m, 2H), 2.40 (s, 3H), 1.90-1.80 (m, 1H), 1.47 (s, 9H), 1.47-1.30 (m, 2H)

[0796] Preparation A3-57: tert-butyl N-[(3S)-1-[2-chloro-5-(4-fluoro-3-methyl-phenyl)-4-pyridyl]-3-piperidyl]carbamate

[0797] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-fluoro-3-methylphenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.01 (s, 1H), 7.35-7.25 (m, 2H), 7.10 (t, 1H), 6.87 (s, 1H), 4.60-4.45 (m, 1H), 3.75-3.65 (m, 1H), 3.25-3.15 (m, 1H), 2.95-2.85 (m, 1H), 2.75-2.65 (m, 2H), 2.36 (s, 3H), 1.85-1.75 (m, 1H), 1.47 (s, 9H), 1.47-1.35 (m, 2H)

[0798] Preparation A3-58: tert-butyl 4-[4-[6-chloro-4-[(3S)-3-(tert-butoxycarbonylamino)-1-piperidyl]-3-pyridyl]pyrazol-1-yl]piperidin-1-carboxylate

[0799] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]piperidin-1-carboxylate. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.85-7.75 (m, 2H), 6.87 (s, 1H), 4.55-4.45 (m, 1H), 4.40-4.20 (m, 2H), 3.80-3.65 (m, 1H), 3.50-3.40 (m, 1H), 3.15-3.05 (m, 1H), 3.00-2.95 (m, 2H), 2.65-2.50 (m, 1H), 2.50-2.45 (m, 1H), 2.30-2.15 (m, 2H), 2.05-1.90 (m, 2H), 1.75-1.65 (m, 1H), 1.65-1.55 (m, 1H), 1.49 (s, 9H), 1.46 (s, 9H), 1.46-1.25 (m, 2H)

[0800] Preparation A3-59: tert-butyl N-[(3S)-1-[2-chloro-5-(4-isopropoxy-3,5-dimethyl-phenyl)-4-pyridyl]-3-piperidyl]carbamate

[0801] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 3,5-dimethyl-4-isopropoxyphenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.12 (s, 2H), 6.82 (s, 1H), 4.70-4.55 (m, 1H), 4.35-4.20 (m, 1H), 3.85-3.70 (m, 1H), 3.30-3.20 (m, 1H), 3.10-3.00 (m, 1H), 2.90-2.80 (m, 1H), 2.34 (s, 6H), 2.00-1.85 (m, 1H), 1.85-1.70 (m, 1H), 1.48 (s, 9H), 1.35 (d, 6H), 1.35-1.25 (m, 2H)

[0802] Preparation A3-60: tert-butyl N-[(3S)-1-[2-chloro-5-(4-methoxy-3,5-dimethyl-phenyl)-4-pyridyl]-3-piperidyl]carbamate

[0803] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-methoxy-3,5-dimethylphenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.02 (s, 1H), 7.13 (s, 2H), 6.83 (s, 1H), 4.65-4.55 (m, 1H), 3.79 (s, 3H), 3.79-3.70 (m, 1H), 3.30-3.20 (m, 1H), 2.90-2.80 (m, 1H), 2.80-2.70 (m, 1H), 2.70-2.60 (m, 1H), 2.36 (s, 6H), 1.80-1.70 (m, 1H), 1.47 (s, 9H), 1.47-1.35 (m, 2H)

[0804] Preparation A3-61: tert-butyl N-[(3S)-1-[2-chloro-5-(4-morpholinophenyl)-4-pyridyl]-3-piperidyl]carbamate

[0805] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to (4-morpholinophenyl)boronic acid. 1H NMR (CDCl3, 400MHz) δ 8.02 (s, 1H), 7.41 (d, 2H), 6.99 (d, 2H), 6.85 (s, 1H), 4.60-4.50 (m, 1H), 3.95-3.90 (m, 4H), 3.90-3.85 (m, 1H), 3.80-3.70 (m, 1H), 3.35-3.30 (m, 1H), 3.30-3.20 (m, 4H), 3.10-3.00 (m, 1H), 3.00-2.90 (m, 1H), 2.70-2.60 (m, 2H), 1.90-1.80 (m, 1H), 1.60-1.55 (m, 1H), 1.48 (s, 9H), 1.48-1.30 (m, 1H)

[0806] Preparation A3-62: tert-butyl N-[(3S)-1-[2-chloro-5-(3-methyl-4-morpholino-phenyl)-4-pyridyl]-3-piperidyl]carbamate

[0807] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 3-methyl-4-morpholinophenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.02 (s, 1H), 7.35-7.25 (m, 2H), 7.10 (d, 2H), 6.84 (s, 1H), 4.60-4.50 (m, 1H), 3.95-3.85 (m, 4H), 3.75-3.65 (m, 1H), 3.30-3.20 (m, 1H), 3.05-2.95 (m, 4H), 2.95-2.90 (m, 1H), 2.75-2.60 (m, 2H), 2.39 (s, 3H), 1.85-1.75 (m, 1H), 1.60-1.50 (m, 1H), 1.46 (s, 9H), 1.46-1.35 (m, 1H)

[0808] Preparation A3-63: tert-butyl N-[(3S)-1-[2-chloro-5-[4-[4-(2-hydroxyethyl)piperazin-1-carbonyl]phenyl]-4-pyridyl]-3-piperidyl]carbamate

[0809] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to [4-[4-(2-hydroxyethyl)piperazin-1-carbonyl]phenyl]boronic acid. 1H NMR (CDCl3, 400MHz) δ 8.04 (s, 1H), 7.60-7.55 (m, 2H), 7.55-7.50 (m, 2H), 6.90 (s, 1H), 4.55-4.45 (m, 1H), 3.90-3.45 (m, 9H), 3.45-3.35 (m, 1H), 3.05-2.95 (m, 1H), 2.70-2.60 (m, 4H), 2.60-2.40 (m, 6H), 1.95-1.80 (m, 1H), 1.47 (s, 9H), 1.47-1.30 (m, 2H)

[0810] Preparation A3-64: tert-butyl N-[(3S)-1-[2-chloro-5-[4-[((trans)4-hydroxycyclohexyl)carbamoyl]phenyl]-4-pyridyl]-3-piperidyl]carbamate

[0811] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-(trans-4-hydroxycyclohexylcarbamoyl)phenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.90-7.80 (m, 2H), 7.60-7.50 (m, 2H), 6.90 (s, 1H), 6.15-6.05 (m, 1H), 4.50-4.40 (m, 1H), 4.10-3.90 (m, 2H), 3.75-3.60 (m, 2H), 3.35-3.25 (m, 1H), 3.05-2.95 (m, 1H), 2.70-2.60 (m, 1H), 2.60-2.50 (m, 1H), 2.25-2.15 (m, 3H), 2.15-2.00 (m, 3H), 1.95-1.80 (m, 1H), 1.60-1.50 (m, 1H), 1.44 (s, 9H), 1.44-1.30 (m, 2H)

[0812] Preparation A3-65: tert-butyl N-[(3S)-1-[2-chloro-5-[4-(dimethylcarbamoyl)-3-fluoro-phenyl]-4-pyridyl]-3-piperidyl]carbamate

[0813] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-(dimethylcarbamoyl)-3-fluorophenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.51 (t, 1H), 7.40-7.35 (m, 1H), 7.35-7.25 (m, 1H), 6.91 (s, 1H), 4.55-4.45 (m, 1H), 3.75-3.65 (m, 1H), 3.50-3.40 (m, 1H), 3.18 (s, 3H), 3.05-2.95 (m, 4H), 2.65-2.55 (m, 2H), 1.95-1.85 (m, 1H), 1.55-1.50 (m, 1H), 1.46 (s, 9H), 1.46-1.30 (m, 1H)

[0814] Preparation A3-66: tert-butyl N-[(3S)-1-[5-(3-acetylphenyl)-2-chloro-4-pyridyl]-3-piperidyl]carbamate

[0815] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 3-acetylphenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 8.07 (s, 1H), 7.97 (d, 1H), 7.70 (d, 1H), 7.58 (t, 1H), 6.91 (s, 1H), 4.65-4.55 (m, 1H), 3.75-3.65 (m, 1H), 3.30-3.20 (m, 1H), 2.95-2.85 (m, 1H), 2.75-2.65 (m, 2H), 2.67 (s, 3H), 1.81 (t, 1H), 1.60-1.50 (m, 1H), 1.45 (s, 9H), 1.45-1.35 (m, 1H)

[0816] Preparation A3-67: tert-butyl N-[(3S)-1-[2-chloro-5-(3-chloro-4-fluoro-phenyl)-4-pyridyl]-3-piperidyl]carbamate

[0817] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 3-chloro-4-fluorophenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.02 (s, 1H), 7.57 (d, 1H), 7.45-7.35 (m, 1H), 7.25-7.15 (m, 1H), 6.89 (s, 1H), 4.55-4.45 (m, 1H), 3.75-3.65 (m, 1H), 3.35-3.25 (m, 1H), 3.00-2.90 (m, 1H), 2.70-2.60 (m, 2H), 1.90-1.80 (m, 1H), 1.55-1.50 (m, 1H), 1.47 (s, 9H), 1.47-1.35 (m, 1H)

[0818] Preparation A3-68: tert-butyl N-[(3S)-1-[2-chloro-5-[4-fluoro-3-(trifluoromethyl)phenyl]-4-pyridyl]-3-piperidyl]carbamate

[0819] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 4-fluoro-3-(trifluoromethyl)phenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.79 (d, 1H), 7.75-7.65 (m, 1H), 7.33 (t, 1H), 6.91 (s, 1H), 4.55-4.40 (m, 1H), 3.75-3.60 (m, 1H), 3.35-3.25 (m, 1H), 3.00-2.90 (m, 1H), 2.70-2.55 (m, 2H), 1.90-1.80 (m, 1H), 1.60-1.50 (m, 1H), 1.46 (s, 9H), 1.46-1.30 (m, 1H)

[0820] Preparation A3-69: tert-butyl N-[(3S)-1-[2-chloro-5-(3,4-difluorophenyl)-4-pyridyl]-3-piperidyl]carbamate

[0821] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 3,4-difluorophenylboronic acid. 1H NMR (CDCl3, 400MHz) δ 8.01 (s, 1H), 7.40-7.30 (m, 1H), 7.25-7.20 (m, 1H), 7.20-7.15 (m, 1H), 6.90 (s, 1H), 4.50-4.40 (m, 1H), 3.75-3.60 (m, 1H), 3.35-3.25 (m, 1H), 3.05-2.95 (m, 1H), 2.75-2.60 (m, 2H), 1.95-1.80 (m, 1H), 1.65-1.55 (m, 1H), 1.47 (s, 9H), 1.47-1.30 (m, 1H)

[0822] Preparation A3-70: tert-butyl N-[(3S)-1-[2-chloro-5-[3-(dimethylamino)-4-fluoro-phenyl]-4-pyridyl]-3-piperidyl]carbamate

[0823] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to (3-(dimethylamino)-4-fluorophenyl)boronic acid. 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.15-7.05 (m, 1H), 7.00-6.95 (m, 1H), 6.95-6.85 (m, 1H), 6.86 (s, 1H), 4.65-4.55 (m, 1H), 3.75-3.65 (m, 1H), 3.30-3.20 (m, 1H), 2.91 (s, 6H), 2.91-2.85 (m, 1H), 2.75-2.65 (m, 2H), 1.85-1.75 (m, 1H), 1.60-1.50 (m, 1H), 1.47 (s, 9H), 1.47-1.35 (m, 1H)

[0824] Preparation A3-71: tert-butyl N-[(3S)-1-[2-chloro-5-[1-[(3S)-tetrahydrofuran-3-yl]pyrazol-4-yl]-4-pyridyl]-3-piperidyl]carbamate

[0825] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to (S)-1-(tetrahydrofuran-3-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.16 (s, 1H), 7.86 (s, 1H), 7.79 (s, 1H), 6.88 (s, 1H), 5.15-5.05 (m, 1H), 4.55-4.45 (m, 1H), 4.25-4.15 (m, 2H), 4.15-4.05 (m, 1H), 3.98 (q, 1H), 3.80-3.70 (m, 1H), 3.45-3.35 (m, 1H), 3.15-3.00 (m, 1H), 2.70-2.60 (m, 1H), 2.60-2.45 (m, 2H), 2.45-2.35 (m, 1H), 2.00-1.90 (m, 1H), 1.75-1.65 (m, 1H), 1.46 (s, 9H), 1.46-1.30 (m, 1H)

[0826] Preparation A3-72: tert-butyl N-[(3S)-1-[2-chloro-5-[1-[(3R)-tetrahydrofuran-3-yl]pyrazol-4-yl]-4-pyridyl]-3-piperidyl]carbamate

[0827] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to (R)-1-(tetrahydrofuran-3-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.85 (s, 1H), 7.78 (s, 1H), 6.87 (s, 1H), 5.10-5.00 (m, 1H), 4.60-4.50 (m, 1H), 4.25-4.15 (m, 2H), 4.15-4.00 (m, 1H), 3.97 (q, 1H), 3.80-3.70 (m, 1H), 3.45-3.35 (m, 1H), 3.15-3.00 (m, 1H), 2.70-2.60 (m, 1H), 2.60-2.45 (m, 2H), 2.45-2.35 (m, 1H), 2.00-1.90 (m, 1H), 1.75-1.65 (m, 1H), 1.46 (s, 9H), 1.46-1.35 (m, 1H)

[0828] Preparation A3-73: tert-butyl (S)-(1-(2-chloro-5-(1-ethyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0829] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.19 (s, 1H), 7.81-7.68 (m, 2H), 6.91 (s, 1H), 4.67-4.42 (m, 1H), 4.37 (q, 2H), 3.87-3.64 (m, 1H), 3.52-3.26 (m, 1H), 3.15-2.99 (m, 1H), 2.75-2.45 (m, 2H), 2.05-1.89 (m, 1H), 1.78-1.65 (m, 1H), 1.62 (t, 3H), 1.53 (s, 9H), 1.41-1.32 (m, 1H)

[0830] Preparation A3-74: tert-butyl (S)-(1-(2-chloro-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0831] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-isopropylpyrazol-4-boronic acid. 1H NMR (CDCl3, 400MHz) δ 8.23 (s, 1H), 7.84-7.67 (m, 2H), 6.91 (s, 1H), 4.65-4.46 (m, 1H), 3.86-3.62 (m, 1H), 3.48-3.32 (m, 1H), 3.14-2.99 (m, 1H), 2.71-2.47 (m, 2H), 2.02-1.88 (m, 1H), 1.74-1.65 (m, 1H), 1.61 (s, 6H), 1.51 (s, 9H), 1.41-1.34 (m, 1H)

[0832] Preparation A3-75: tert-butyl (S)-(1-(2-chloro-5-(1-cyclopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0833] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.18 (s, 1H), 7.83 (s, 1H), 7.76 (s, 1H), 6.90 (s, 1H), 4.62-4.43 (m, 1H), 3.84-3.63 (m, 2H), 3.49-3.37 (m, 1H), 3.14-3.01 (m, 1H), 2.70-2.45 (m, 2H), 2.04-1.89 (m, 1H), 1.76-1.65 (m, 1H), 1.59-1.52 (m, 1H), 1.52 (s, 9H), 1.41-1.33 (m, 1H), 1.33-1.25 (m, 2H), 1.24-1.21 (m, 1H), 1.14-1.01 (m, 2H)

[0834] Preparation A3-76: tert-butyl (S)-(1-(2-chloro-5-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0835] The titled compound was prepared in accordance with the same procedures as in Preparation A3-1, changing the boronic acid reagent to 1-cyclopropylmethyl-1H-pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.19 (s, 1H), 7.91 (s, 1H), 7.79 (s, 1H), 6.89 (s, 1H), 4.66 (s, 1H), 4.10 (d, 2H), 3.85-3.68 (m, 1H), 3.46-3.31 (m, 1H), 3.11-2.99 (m, 1H), 2.72-2.50 (m, 2H), 1.98-1.89 (m, 1H), 1.78-1.64 (m, 1H), 1.64-1.50 (m, 1H), 1.42-1.33 (m, 2H), 1.33 (s, 9H), 0.76-0.66 (m, 2H), 0.50-0.35 (m, 2H)

[0836] Preparation A4-1: (S)-1-(6-chloro-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol

[0837] Step 1: (S)-1-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-4-yl)piperidin-3-ol (A4)

[0838] 2-Chloro-4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (3.0 g, 11.65 mmol) was dissolved in anhydrous isopropyl alcohol (58.2 mL) and then (S)-3-hydroxypiperidine hydrochloride (1.8 g, 12.82 mmol) and diisopropylethylamine (4.8 mL, 34.95 mmol) were added dropwise thereto. The reaction mixture was stirred at 50℃ for 7 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated to prepare the titled compound, which was used in the subsequent step without further purification.

[0839] Step 2: (S)-1-(6-chloro-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol (A4-1)

[0840] (S)-1-(2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-4-yl)piperidin-3-ol (100.0 mg, 0.30 mmol) was dissolved in anhydrous 1,4-dioxane(2.0 mL) and then 5-bromo-2-tetrahydropyran-4-yl-pyridine (85.8 mg, 0.35 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (24.1 mg, 0.03 mmol), and 2.0M sodium carbonate solution (0.71 mL, 1.43 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 80℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (20.1 mg). (Yield: 18.2%) 1H NMR (CDCl3, 400MHz) δ 8.69 (s, 1H), 8.03 (s, 1H), 7.78 (d, 1H), 7.28 (d, 1H), 6.90 (s, 1H), 4.14-4.11 (m, 2H), 3.61-3.60 (m, 1H), 3.59-3.55 (m, 2H), 3.21-3.20 (m, 1H), 3.17-3.04 (m, 2H), 2.72-2.67 (m, 2H), 1.96-1.91 (m, 5H), 1.66-1.64 (m, 1H), 1.46-1.44 (m, 2H), 1.42-1.41 (m, 1H)

[0841] Preparation A4-2: (S)-1-(6-chloro-6'-((4-methylpiperazin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol

[0842] The titled compound was prepared in accordance with the same procedures as in Preparation A4-1, changing the bromine reagent to 1-((5-bromopyridin-2-yl)methyl)-4-methylpiperazine. 1H NMR (CDCl3, 400MHz) δ 8.73 (s, 1H), 8.05 (s, 1H), 7.79-7.77 (m, 1H), 7.46 (d, 1H), 6.90 (s, 1H), 3.81 (s, 2H), 3.65-3.57 (m, 1H), 3.06-3.02 (m, 2H), 2.75-2.71 (m, 1H), 2.61-2.51 (m, 9H), 2.32-2.28 (m, 4H), 1.89-1.83 (m, 2H), 1.52-1.35 (m, 2H)

[0843] Preparation A4-3: (S)-1-(6-chloro-6'-(morpholinomethyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol

[0844] The titled compound was prepared in accordance with the same procedures as in Preparation A4-1, changing the bromine reagent to 4-((5-bromopyridin-2-yl)methyl)morpholine. 1H NMR (CDCl3, 400MHz) δ 8.73 (s, 1H), 8.04 (s, 1H), 7.81 (d, 1H), 7.53-7.51 (m, 1H), 6.91 (s, 1H), 3.78-3.76 (m, 4H), 3.73-3.72 (m, 3H), 3.20-3.17 (m, 1H), 2.98-2.93 (m, 1H), 2.76-2.66 (m, 2H), 2.67-2.53 (m, 4H), 1.88-1.86 (m, 1H), 1.67-1.63 (m, 1H), 1.49-1.41 (m, 2H)

[0845] Preparation A4-4: (S)-1-(6-chloro-6'-((4-hydroxypiperidin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol

[0846] The titled compound was prepared in accordance with the same procedures as in Preparation A4-1, changing the bromine reagent to 1-[(5-bromo-2-pyridyl)methyl]piperidin-4-ol. 1H NMR (CDCl3, 400MHz) δ 8.71 (s, 1H), 8.05 (s, 1H), 7.80 (d, 1H), 7.53-7.51 (m, 1H), 6.91 (s, 1H), 3.84-3.66 (m, 4H), 3.18-3.16 (m, 1H), 3.00-2.97 (m, 1H), 2.82-2.63 (m, 4H), 2.35-2.26 (m, 2H), 1.93-1.86 (m, 3H), 1.76-1.65 (m, 3H), 1.47-1.43 (m, 3H)

[0847] Preparation A4-5: (S)-(6'-chloro-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(4-methylpiperazin-1-yl)methanone

[0848] The titled compound was prepared in accordance with the same procedures as in Preparation A4-1, changing the bromine reagent to (5-bromopyridin-2-yl)(4-methylpiperazin-1-yl)methanone. 1H NMR (CDCl3, 400MHz) δ 8.76 (s, 1H), 8.38 (s, 1H), 8.05-7.95 (m, 2H), 6.93 (s, 1H), 3.87-3.86 (m, 2H), 3.69-3.68 (m, 2H), 3.63-3.61 (m, 1H), 3.19-3.16 (m, 1H), 3.04-2.99 (m, 1H), 2.70-2.65 (m, 2H), 2.56-2.54 (m, 2H), 2.49-2.46 (m, 2H), 2.35 (s, 3H), 1.90-1.81 (m, 2H), 1.73-1.70 (m, 1H), 1.45-1.42 (m, 2H)

[0849] Preparation A4-6: (S)-(6'-chloro-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(morpholino)methanone

[0850] The titled compound was prepared in accordance with the same procedures as in Preparation A4-1, changing the bromine reagent to (5-bromopyridin-2-yl)(morpholino)methanone. 1H NMR (CDCl3, 400MHz) δ 8.75 (s, 1H), 8.05 (s, 1H), 8.00-7.97 (m, 1H), 7.86-7.81 (m, 1H), 6.94 (s, 1H), 3.85 (s, 4H), 3.74 (s, 4H), 3.19-3.16 (m, 1H), 3.03-2.96 (m, 1H), 2.80-2.69 (m, 2H), 1.92-1.85 (m, 1H), 1.74-1.68 (m, 2H), 1.47-1.43 (m, 2H)

[0851] Preparation A4-7: (S)-(6'-chloro-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(4-hydroxypiperidin-1-yl)methanone

[0852] The titled compound was prepared in accordance with the same procedures as in Preparation A4-1, changing the bromine reagent to (5-bromopyridin-2-yl)(4-hydroxypiperidin-1-yl)methanone. 1H NMR (CDCl3, 400MHz) δ 8.76 (s, 1H), 8.06 (s, 1H), 7.96 (d, 1H), 7.54 (d, 1H), 6.93 (s, 1H), 4.26-4.23 (m, 1H), 4.04-4.03 (m, 1H), 3.91-3.87 (m, 1H), 3.75-3.67 (m, 1H), 3.51-3.46 (m, 1H), 3.40-3.35 (m, 1H), 3.19-3.16 (m, 1H), 3.02-2.98 (m, 1H), 2.78-2.65 (m, 2H), 2.08-2.03 (m, 1H), 2.01-1.89 (m, 3H), 1.71-1.64 (m, 2H), 1.47-1.44 (m, 2H)

[0853] Preparation A4-8: (S)-6'-chloro-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-carbaldehyde

[0854] The titled compound was prepared in accordance with the same procedures as in Preparation A4-1, changing the bromine reagent to 5-bromo-2-pyridinecarboxaldehyde. 1H NMR (CDCl3, 400MHz) δ 10.13 (s, 1H), 8.97 (s, 1H), 8.07 (d, 3H), 6.96 (s, 1H), 3.77-3.76 (m, 1H), 3.23-3.19 (m, 1H), 2.99-2.96 (m, 1H), 2.78-2.71 (m, 2H), 1.95-1.92 (m, 1H), 1.71-1.68 (m, 1H), 1.52-1.50 (m, 1H), 1.47-1.43 (m, 2H)

[0855] Preparation A4-9: (S)-1-(6'-chloro-5-((1-methylpiperidin-4-yl)oxy)-[2,3'-bipyridin]-4'-yl)piperidin-3-ol

[0856] The titled compound was prepared in accordance with the same procedures as in Preparation A4-1, changing the bromine reagent to 2-bromo-5-[(1-methyl-4-piperidyl)oxy]pyridine. 1H NMR (CD3OD, 400MHz) δ 8.43 (s, 1H), 8.08 (s, 1H), 7.75 (d, 1H), 7.62 (d, 1H), 7.05 (s, 1H), 3.70-3.60 (m, 2H), 3.55-3.40 (m, 3H), 3.30-3.20 (m, 1H), 3.15-3.05 (m, 1H), 2.93 (s, 3H), 2.74 (t, 1H), 2.61 (t, 1H), 2.35-2.10 (m, 3H), 2.10-2.00 (m, 1H), 2.00-1.90 (m, 1H), 1.80-1.65 (m, 1H), 1.50-1.25 (m, 3H)

[0857] Preparation A5-1: tert-butyl (S)-(1-(6-chloro-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate

[0858] Step 1: tert-butyl (S)-(1-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0859] 2-Chloro-4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2.0 g, 7.77 mmol) was dissolved in anhydrous isopropyl alcohol (38.8 mL) and then (S)-3-(tert-butoxycarbonylamino)piperidine (2.33 g, 11.65 mmol) and diisopropylethylamine (3.2 mL, 23.30 mmol) were added dropwise thereto. The reaction mixture was stirred at 50℃ for 8 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (1.0 g). (Yield: 29.4%) 1H NMR (CDCl3, 400MHz) δ 8.48 (s, 1H), 6.73 (s, 1H), 5.37-5.36 (m, 1H), 3.92-3.89 (m, 1H), 3.19-3.12 (m, 3H), 3.04-3.01 (m, 1H), 1.96-1.95 (m, 1H), 1.82-1.79 (m, 1H), 1.72-1.68 (m, 2H), 1.46 (s, 6H), 1.38 (s, 6H)

[0860] Step 2: tert-butyl (S)-(1-(6-chloro-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-4-yl)piperidin-3-yl)carbamate (A5-1)

[0861] tert-Butyl (S)-(1-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-4-yl)piperidin-3-yl)carbamate (150.0 mg, 0.34 mmol) was dissolved in anhydrous 1,4-dioxane (3.40 mL) and then 5-bromo-2-tetrahydropyran-4-yl-pyridine (99.5 mg, 0.41 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (27.9 mg, 0.034 mmol), and 2.0M sodium carbonate solution (0.69 mL, 1.37 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 80℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (51.0 mg). (Yield: 31.5%) 1H NMR (CDCl3, 400MHz) δ 8.65 (s, 1H), 8.03 (s, 1H), 7.82 (d, 1H), 7.28 (s, 1H), 6.89 (s, 1H), 4.51-4.41 (m, 1H), 4.14-4.11 (m, 2H), 3.61-3.55 (m, 3H), 3.37-3.34 (m, 1H), 3.04-2.98 (m, 2H), 2.64-2.54 (m, 2H), 1.94-1.82 (m, 4H), 1.54-1.53 (m, 1H), 1.43 (s, 9H), 1.29-1.27 (m, 1H)

[0862] Preparation A5-2: tert-butyl N-[(3S)-1-[2-chloro-5-[6-(1-methyl-4-piperidyl)-3-pyridyl]-4-pyridyl]-3-piperidyl]carbamate

[0863] The titled compound was prepared in accordance with the same procedures as in Preparation A5-1, changing the bromine reagent to 5-bromo-2-(1-methyl-4-piperidyl)pyridine. 1H NMR (CDCl3, 400MHz) δ 8.63 (s, 1H), 8.02 (s, 1H), 7.79 (d, 1H), 7.29 (d, 1H), 6.88 (s, 1H), 4.52-4.44 (m, 1H), 3.72-3.65 (m, 1H), 3.37-3.34 (m, 1H), 3.04-2.94 (m, 4H), 2.79-2.72 (m, 2H), 2.63-2.55 (m, 2H), 2.35 (s, 3H), 2.14-2.12 (m, 2H), 2.09-2.05 (m, 2H), 2.01-1.87 (m, 4H), 1.45 (s, 9H)

[0864] Preparation A5-3: tert-butyl (S)-(1-(2-chloro-5-(2-(1-methylpiperidin-4-yl)thiazol-5-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0865] The titled compound was prepared in accordance with the same procedures as in Preparation A5-1, changing the bromine reagent to 5-bromo-2-(1-methyl-4-piperidinyl)thiazole. 1H NMR (CD3OD, 400MHz) δ 8.46 (s, 1H), 8.18 (s, 1H), 7.93 (s, 1H), 3.89-3.56 (m, 3H), 3.44 (t, 1H), 3.35 (d, 1H), 3.20-3.14 (m, 3H), 2.88 (s, 3H), 2.71 (t, 1H), 2.41 (d, 3H), 2.24-2.17 (m, 2H), 1.93 (d, 1H), 1.78 (brs, 1H), 1.70-1.66 (m, 1H), 1.40 (s, 9H), 1.39-1.25 (m, 1H)

[0866] Preparation A6-1: (S)-1-(2-chloro-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol

[0867] (S)-1-(2-Chloro-5-iodopyridin-4-yl)piperidin-3-ol (A2, 500.0 mg, 1.48 mmol) was dissolved in anhydrous 1,4-dioxane (10.0 mL) and then 4-ethynyl-1-(trifluoromethyl)-1H-pyrazole (354.6 mg, 2.21 mmol), bis(triphenylphosphine)palladium(II) dichloride (51.8 mg, 0.074 mmol), copper(I) iodide (16.9 mg, 0.089 mmol), and triethylamine (0.41 mL, 2.95 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 80℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (491.7 mg). (Yield: 89.8%) 1H NMR (CDCl3, 400MHz) δ 8.30 (s, 1H), 8.11 (s, 1H), 7.93 (s, 1H), 6.80 (s, 1H), 4.02-4.01 (m, 1H), 3.55-3.51 (m, 2H), 3.36-3.34 (m, 2H), 2.12-1.89 (m, 2H), 1.77-1.72 (m, 2H)

[0868] Preparation A6-2: (S)-1-(2-chloro-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol

[0869] The titled compound was prepared in accordance with the same procedures as in Preparation A6-1, changing the ethyne reagent to 4-ethynyl-tetrahydro-2H-pyrane. 1H NMR (CDCl3, 400MHz) δ 8.19 (s, 1H), 6.74 (s, 1H), 3.99-3.94 (m, 3H), 3.61-3.52 (m, 3H), 3.40-3.37 (m, 1H), 3.33-3.28 (m, 1H), 3.24-3.22 (m, 1H), 3.80 (s, 1H), 2.20-2.19 (m, 1H), 1.98-1.92 (m, 4H), 1.85-1.82 (m, 2H)

[0870] Preparation A6-3: (S)-1-(2-chloro-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol

[0871] The titled compound was prepared in accordance with the same procedures as in Preparation A6-1, changing the ethyne reagent to 1-(difluoromethyl)-4-ethynyl-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.33 (s, 1H), 8.13 (s, 1H), 7.88 (s, 1H), 7.38-7.35 (m, 0.2H), 7.23-7.19 (m, 0.6H), 7.08-7.04 (m, 0.2H), 6.84 (s, 1H), 4.07-3.97 (m, 1H), 3.50-3.44 (m, 1H), 3.43-3.33 (m, 1H), 3.33-3.26 (m, 1H), 2.23-2.12 (m, 1H), 2.06-1.85 (m, 1H), 1.83-1.69 (m, 2H)

[0872] Preparation A6-4: (S)-1-(2-chloro-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol

[0873] The titled compound was prepared in accordance with the same procedures as in Preparation A6-1, changing the ethyne reagent to 1-(2,2-difluoroethyl)-4-ethynyl-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.33-8.34 (s, 1H), 7.81 (s, 2H), 6.83 (s, 1H), 6.30-6.24 (m, 0.2H), 6.16-6.10 (m, 0.6H), 6.01-5.97 (m, 0.2H), 4.56-4.44 (m, 2H), 4.07-3.97 (m, 1H), 3.59-3.47 (m, 2H), 3.41-3.27 (m, 2H), 2.07-1.95 (m, 1H), 1.95-1.86 (m, 1H), 1.80-1.70 (m, 2H)

[0874] Preparation A6-5: (S)-1-(2-chloro-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol

[0875] The titled compound was prepared in accordance with the same procedures as in Preparation A6-1, changing the ethyne reagent to 4-ethynyl-1-(2,2,2-trifluoroethyl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.33 (s, 1H), 7.84 (s, 1H), 7.81 (s, 1H), 6.82 (s, 1H), 4.07-3.97 (m, 1H), 3.59-3.46 (m, 2H), 3.40-3.25 (m, 2H), 2.19-2.14 (m, 1H), 1.95-1.84 (m, 1H), 1.81-1.69 (m, 2H)

[0876] Preparation A7-1: tert-butyl (S)-(1-(2-chloro-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0877] tert-Butyl (S)-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)carbamate(300.0 mg, 0.68 mmol) was dissolved in anhydrous 1,4-dioxane (8.0 mL) and then 4-ethynyl-tetrahydro-2H-pyrane (150.9 mg, 1.37 mmol), bis(triphenylphosphine)palladium(II) dichloride (22.9 mg, 0.033 mmol), copper(I) iodide (7.8 mg, 0.041 mmol), and triethylamine (0.19 mL, 1.37 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 80℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (120.4 mg). (Yield: 41.8%) 1H NMR (CDCl3, 400MHz) δ 8.19 (s, 1H), 7.27 (s, 1H), 4.89-4.88 (m, 1H), 3.97-3.95 (m, 2H), 3.93-3.91 (m, 1H), 3.57-3.52 (m, 3H), 3.39-3.37 (m, 1H), 3.20-3.19 (m, 2H), 2.96-2.92 (m, 1H), 1.94-1.92 (m, 2H), 1.86-1.63 (m, 6H), 1.43 (s, 9H)

[0878] Preparation A7-2: tert-butyl (S)-(1-(2-chloro-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0879] The titled compound was prepared in accordance with the same procedures as in Preparation A7-1, changing the ethyne reagent to 4-ethynyl-1-(trifluoromethyl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.29-8.28 (m, 2H), 7.92 (s, 1H), 6.79 (s, 1H), 4.74-4.73 (m, 1H), 3.89-3.74 (m, 2H), 3.39-3.21 (m, 1H), 3.08-2.99 (m, 1H), 1.92-1.87 (m, 2H), 1.77-1.75 (m, 1H), 1.58-1.55 (m, 1H), 1.42 (s, 9H)

[0880] Preparation A7-3: tert-butyl (S)-(1-(2-chloro-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0881] The titled compound was prepared in accordance with the same procedures as in Preparation A7-1, changing the ethyne reagent to 1-(difluoromethyl)-4-ethynyl-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.28 (s, 1H), 8.19 (s, 1H), 7.82 (s, 1H), 7.33-7.03 (m, 1H), 6.77 (s, 1H), 4.80-4.78 (m, 1H), 3.88 (brs, 1H), 3.80-3.77 (m, 1H), 3.41-3.38 (m, 1H), 3.12-3.11 (m, 2H), 1.92-1.88 (m, 2H), 1.76-1.75 (m, 1H), 1.74-1.73 (m, 1H), 1.42 (s, 9H)

[0882] Preparation A7-4: tert-butyl (S)-(1-(2-chloro-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0883] The titled compound was prepared in accordance with the same procedures as in Preparation A7-1, changing the ethyne reagent to 1-(2,2-difluoroethyl)-4-ethynyl-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.26 (s, 1H), 7.81 (s, 1H), 7.74 (s, 1H), 6.76 (s, 1H), 6.25-5.95 (m, 1H), 4.82-4.80 (m, 1H), 4.50-4.42 (m, 2H), 3.87-3.86 (m, 1H), 3.72-3.69 (m, 1H), 3.43-3.40 (m, 1H), 3.17-3.15 (m, 2H), 1.92-1.88 (m, 2H), 1.75-1.74 (m, 1H), 1.73-1.71 (m, 1H), 1.43 (s, 9H)

[0884] Preparation A7-5: tert-butyl (S)-(1-(2-chloro-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0885] The titled compound was prepared in accordance with the same procedures as in Preparation A7-1, changing the ethyne reagent to 4-ethynyl-1-(2,2,2-trifluoroethyl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.27 (s, 1H), 7.86 (s, 1H), 7.76 (s, 1H), 6.76 (s, 1H), 4.80-4.78 (m, 1H), 4.73-4.67 (q, 2H), 3.87-3.86 (m, 1H), 3.75-3.72 (m, 1H), 3.44-3.41 (m, 1H), 3.16-3.11 (m, 2H), 1.92-1.88 (m, 2H), 1.76-1.74 (m, 1H), 1.72-1.70 (m, 1H), 1.42 (s, 9H)

[0886] Preparation A7-6: tert-butyl (S)-(1-(2-chloro-5-((4-methyltetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0887] The titled compound was prepared in accordance with the same procedures as in Preparation A7-1, changing the ethyne reagent to 4-ethynyl-4-methyltetrahydro-2H-pyrane. 1H NMR (CDCl3, 400MHz) δ 8.66 (s, 1H), 6.86 (s, 1H), 5.03-4.84 (m, 1H), 3.96 (s, 1H), 3.88-3.82 (m, 3H), 3.24-3.19 (m, 1H), 3.10-2.94 (m, 2H), 2.88-2.78 (m, 1H), 2.10-2.02 (m, 2H), 1.38 (s, 9H)

[0888] Preparation A7-7: tert-butyl (S)-(1-(2-chloro-5-((4-hydroxytetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)piperidin-3-yl)carbamate

[0889] The titled compound was prepared in accordance with the same procedures as in Preparation A7-1, changing the ethyne reagent to 4-ethynyltetrahydro-2H-pyran-4-ol. 1H NMR (CDCl3, 400MHz) δ 8.29 (s, 1H), 6.80 (s, 1H), 4.65-4.50 (m, 2H), 4.03-3.92 (m, 2H), 3.90-3.80 (m, 1H), 3.80-3.70 (m, 2H), 3.40-3.29 (m, 1H), 2.86-2.73 (m, 1H), 2.37-2.26 (m, 1H), 2.15-2.09 (m, 2H), 2.03-1.93 (m, 3H), 1.87-1.75 (m, 1H), 1.55 (s, 9H)

[0890] Preparation A7-8: tert-butyl (S)-(1-(2-chloro-5-(3-hydroxy-3-methylbut-1-yn-1-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0891] The titled compound was prepared in accordance with the same procedures as in Preparation A7-1, changing the ethyne reagent to 2-methylbut-3-yn-2-ol. 1H NMR (CDCl3, 400MHz) δ 8.26 (s, 1H), 6.80 (s, 1H), 4.64-4.53 (m, 1H), 4.53-4.42 (m, 1H), 3.98-3.78 (m, 1H), 3.36-3.25 (m, 1H), 2.91-2.74 (m, 1H), 2.47-2.32 (m, 1H), 2.11-2.00 (m, 1H), 2.00-1.87 (m, 1H), 1.87-1.78 (m, 1H), 1.70 (s, 6H), 1.52 (s, 9H)

[0892] Preparation A7-9: tert-butyl (S)-(1-(2-chloro-5-(4-hydroxybut-1-yn-1-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[0893] The titled compound was prepared in accordance with the same procedures as in Preparation A7-1, changing the ethyne reagent to 3-butyn-1-ol. 1H NMR (CDCl3, 400MHz) δ 8.27 (s, 1H), 6.80 (s, 1H), 4.90-4.80 (m, 1H), 4.20 (q, 2H), 3.82-3.74 (m, 1H), 3.35-3.22 (m, 1H), 3.12-3.04 (m, 2H), 1.99-1.85 (m, 2H), 1.82-1.71 (m, 1H), 1.54 (s, 9H), 1.33 (t, 2H)

[0894] Preparation A8-1: (S)-1-(6-chloro-6'-(((S)-3-fluoropyrrolidin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol

[0895] (S)-6'-chloro-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-carbaldehyde(A4-8, 40 mg, 0.13 mmol) was dissolved in dichloromethane (1.0 mL) and then (S)-(+)-3-fluoropyrrolidine hydrochloride (13.0 mg, 0.10 mmol) and triethylamine (0.03 ml, 0.19 mmol) were added dropwise thereto. Then, the mixed solution was stirred at room temperature for 10 minutes. The reaction mixture was cooled to 0℃ with ice water and then sodium borohydride (60.0 mg, 0.28 mmol) was added dropwise thereto. The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, dichloromethane was added to the reaction mixture and then a saturated sodium hydrogen carbonate solution was added thereto. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated to prepare the titled compound (22.5 mg), without further purification. (Yield: 61.0%) 1H NMR (CDCl3, 400MHz) δ 8.67 (s, 1H), 8.03-7.99 (m, 2H), 7.64 (d, 1H), 7.06 (s, 1H), 3.87 (s, 2H), 3.60-3.57 (m, 1H), 3.28-3.25 (m, 2H), 3.12-3.08 (m, 1H), 3.02-2.92 (m, 2H), 2.79-2.71 (m, 1H), 2.59-2.53 (m, 2H), 2.25-2.10 (m, 1H), 2.07-1.91 (m, 2H), 1.70-1.66 (m, 1H), 1.44-1.25 (m, 3H)

[0896] Preparation A8-2: (3S)-1-[2-chloro-5-[6-[(3-hydroxypyrrolidin-1-yl)methyl]-3-pyridyl]-4-pyridyl]piperidin-3-ol

[0897] The titled compound was prepared in accordance with the same procedures as in Preparation A8-1, changing the amine reagent to pyrrolidin-3-ol. 1H NMR (CDCl3, 400MHz) δ 8.70 (s, 1H), 8.02-7.99 (m, 2H), 7.64 (d, 1H), 7.07 (s, 1H), 4.41 (brs, 1H), 4.01-3.99 (m, 2H), 3.60-3.56 (m, 1H), 3.28-3.25 (m, 1H), 3.12-3.09 (m, 1H), 2.99-2.98 (m, 2H), 2.79-2.69 (m, 3H), 2.57 (t, 1H), 2.23-2.16 (m, 1H), 2.02-1.91 (m, 1H), 1.83-1.80 (m, 1H), 1.70-1.67 (m, 1H), 1.44-1.25 (m, 3H)

[0898] Preparation A8-3: (3S)-1-[2-chloro-5-[6-[[3-(dimethylamino)pyrrolidin-1-yl]methyl]-3-pyridyl]-4-pyridyl]piperidin-3-ol

[0899] The titled compound was prepared in accordance with the same procedures as in Preparation A8-1, changing the amine reagent to 3-(dimethylamino)pyrrolidine. 1H NMR (CDCl3, 400MHz) δ 8.70 (s, 1H), 8.05 (s, 1H), 7.80-7.75 (m, 1H), 7.46 (d, 1H), 6.90 (s, 1H), 7.38 (d, 1H), 6.89 (d, 1H), 3.98 (s, 2H), 3.55-3.52 (m, 1H), 3.08-3.04 (m, 2H), 2.85-2.78 (m, 6H), 2.49-2.47 (m, 1H), 2.38-2.34 (m, 4H), 2.22 (s, 6H), 2.03-1.99 (m, 1H), 2.22 (s, 1H), 1.79-1.72 (m, 1H)

[0900] Preparation A8-4: 1-((6'-chloro-4'-((S)-3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)methyl)piperidin-3-ol

[0901] The titled compound was prepared in accordance with the same procedures as in Preparation A8-1, changing the amine reagent to 3-hydroxypiperidine. 1H NMR (CDCl3, 400MHz) δ 8.80-8.70 (m, 1H), 8.05 (s, 1H), 7.84-7.78 (m, 1H), 7.51-7.45 (m, 1H), 6.90 (d, 1H), 3.85-3.82 (m, 2H), 3.61-3.58 (m, 1H), 3.14-3.03 (m, 3H), 2.76-2.71 (m, 2H), 2.56-2.38 (m, 7H), 1.95-1.87 (m, 5H), 1.48-1.39 (m, 2H)

[0902] Preparation A8-5: tert-butyl (S)-(1-((6'-chloro-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)methyl)piperidin-4-yl)carbamate

[0903] The titled compound was prepared in accordance with the same procedures as in Preparation A8-1, changing the amine reagent to 4-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.68 (s, 1H), 8.00 (s, 2H), 7.63 (d, 1H), 7.07 (s, 1H), 3.75 (s, 2H), 3.60-3.58 (m, 1H), 3.60-3.56 (m, 1H), 3.38-3.23 (m, 2H), 3.14-3.08 (m, 1H), 2.94-2.91 (m, 2H), 2.73-2.68 (m, 1H), 2.57 (t, 1H), 2.30-2.20 (m, 2H), 1.94-1.85 (m, 3H), 1.72-1.65 (m, 1H), 1.57-1.52 (m, 2H), 1.44 (s, 9H), 1.36-1.34 (m, 1H)

[0904] Preparation A9-1: (S)-1-(2-chloro-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyrimidin-4-yl)piperidin-3-ol

[0905] Step 1: (S)-1-(2-chloro-5-iodopyrimidin-4-yl)piperidin-3-ol (A9)

[0906] 2,4-Dichloro-5-iodo-pyrimidine (500 mg, 1.82 mmol) was dissolved in anhydrous acetonitrile (10.0 mL) and the (S)-3-hydroxypiperidine hydrochloride (275.3 mg, 2.00 mmol) and diisopropylethylamine (1.6 mL, 11.65 mmol) were added dropwise thereto. The reaction mixture was stirred 50℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (290 mg). (Yield: 46.9%) 1H NMR (CDCl3, 400MHz) δ 8.48 (s, 1H), 3.99 (s, 1H), 3.85 (d, 1H), 3.71 / 3.67 (m, 1H), 3.62-3.52 (m, 2H), 2.29-2.28 (m, 1H), 1.95-1.93 (m, 2H), 1.74-1.61 (m, 2H)

[0907] Step 2: (S)-1-(2-chloro-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyrimidin-4-yl)piperidin-3-ol (A9-1)

[0908] (S)-1-(2-Chloro-5-iodopyrimidin-4-yl)piperidin-3-ol (200 mg, 0.59 mmol) was dissolved in anhydrous 1,4-dioxane (6.0 mL) and then 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine (205.8 mg, 0.71 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (48.2 mg, 0.06 mmol), and 2.0M sodium carbonate solution (1.48 mL, 2.95 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 80℃ for 6 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (50.0 mg). (Yield: 22.5%) 1H NMR (CDCl3, 400MHz) δ 8.03 (s, 1H), 7.60 (s, 1H), 7.59 (s, 1H), 4.19-4.15 (m, 1H), 3.90-3.88 (m, 1H), 3.59-3.58 (m, 1H), 3.56-3.55 (m, 1H), 3.48-3.44 (m, 1H), 3.32-3.29 (m, 1H), 3.22-3.02 (m, 2H), 2.34 (s, 3H), 2.22-2.03 (m, 6H), 1.85-1.82 (m, 1H), 1.78-1.75 (m, 1H), 1.66-1.63 (m, 1H), 1.45-1.44 (m, 1H)

[0909] Preparation A10-1: tert-butyl (S)-(1-(6-chloro-3-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridazin-4-yl)piperidin-3-yl) carbamate

[0910] Step 1: tert-butyl (S)-(1-(3-bromo-6-chloropyridazin-4-yl)piperidin-3-yl)carbamate (A10)

[0911] 3-Bromo-4,6-dichloropyridazine (500.0 mg, 2.19 mmol) was dissolved in anhydrous dimethylacetamide (5.0 mL) and then (S)-3-(tert-butoxycarbonylamino)piperidine (659.1 mg, 3.29 mmol) and diisopropylethylamine (1.15 mL, 6.58 mmol) were added dropwise thereto. The reaction mixture was stirred at 90℃ for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (700.0 mg). (Yield: 81.6%) 1H NMR (CDCl3, 400MHz) δ 6.88 (s, 1H), 4.83 (s, 1H), 3.91 (s, 1H), 3.51-3.48 (m, 1H), 3.39-3.34 (m, 1H), 3.14-3.11 (m, 1H), 3.09-3.00 (m, 1H), 1.97-1.90 (m, 2H), 1.89-1.85 (m, 1H), 1.72 (s, 9H), 1.70-1.68 (m, 1H)

[0912] Step 2: tert-butyl (S)-(1-(6-chloro-3-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridazin-4-yl)piperidin-3-yl) carbamate (A10-1)

[0913] tert-Butyl (S)-(1-(6-chloro-3-bromopyridazin-4-yl)piperidin-3-yl)carbamate (100 mg, 0.25 mmol) was dissolved in anhydrous 1,4-dioxane (3.0 mL) and then 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole (70.5 mg, 0.25 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (10.4 mg, 0.013 mmol), and 2.0M sodium carbonate solution (0.38 mL, 0.76 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 90℃ overnight. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (75.4 mg). (Yield: 64.0%) 1H NMR (CDCl3, 400MHz) δ 8.25 (s, 1H), 8.24 (s, 1H), 7.00 (s, 1H), 4.89-4.81 (m, 2H), 4.52-4.51 (m, 1H), 3.80 (s, 1H), 3.56-3.53 (m, 1H), 3.24-3.21 (m, 1H), 2.68-2.67 (m, 1H), 2.50-2.49 (m, 1H), 2.04-2.03 (m, 1H), 1.85-1.82 (m, 1H), 1.81-1.80 (m, 1H), 1.73 (s, 9H), 1.40-1.39 (m, 1H)

[0914] Preparation A11-1: methyl (S)-6-chloro-4-(3-hydroxypiperidin-1-yl)nicotinate

[0915] Methyl-4,6-dichloronicotinate (1.0 g, 4.85 mmol) was dissolved in anhydrous dimethylformamide (20.0 mL) and then (S)-3-hydroxypiperidine hydrochloride (734.7 mg, 5.34 mmol) and diisopropylethylamine (1.7 mL, 9.71 mmol) were added dropwise thereto. The reaction mixture was stirred at 50℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature. Water was added to the reaction mixture and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (1.13 g, Yield: 86.0%). 1H NMR (CDCl3, 400MHz) δ 8.60 (s, 1H), 6.86 (s, 1H), 4.00-3.97 (m, 1H), 3.94 (s, 3H), 3.24-3.18 (m, 3H), 3.14-3.09 (m, 1H), 2.90 -2.87 (m, 1H), 2.07-2.03 (m, 1H), 1.83-1.75 (m, 2H), 1.70-1.63 (m, 1H)

[0916] Preparation A11-2: (S)-6-chloro-4-(3-hydroxypiperidin-1-yl)nicotinamide

[0917] The titled compound was prepared in accordance with the same procedures as in Preparation A11-1, changing the dichloro reagent to 4,6-dichloronicotinamide. 1H NMR (CD3OD, 400MHz) δ 8.20 (s, 1H), 7.00 (s, 1H), 3.86-3.82 (m, 1H), 3.54-3.50 (m, 1H), 3.39-3.36 (m, 1H), 3.11-3.05 (m, 1H), 2.97-2.92 (m, 1H), 2.03-1.89 (m, 2H), 1.69-1.65 (m, 1H), 1.57-1.2 (m, 1H)

[0918] Preparation B1-1: tert-butyl (S)-(1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)(methyl)carbamate

[0919] Step 1: 2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-fluoropyridine (B1)

[0920] 2-Chloro-4-fluoro-5-iodo-pyridine (5.0 g, 19.42 mmol) was dissolved in anhydrous 1,4-dioxane (97.1 mL) and then 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester (5.7 g, 23.30 mmol), bis(triphenylphosphine)palladium(II) dichloride (1.36 g, 1.94 mmol), and 2.0M sodium carbonate solution (29.1 mL, 58.3 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 80℃ for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (3.7 g). (Yield: 76.9%) 1H NMR (CDCl3, 400MHz) δ 8.63 (d, 1H), 8.23 (s, 1H), 8.04 (s, 1H), 7.41-7.11 (m, 2H)

[0921] Step 2: tert-butyl (S)-(1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)(methyl)carbamate (B1-1)

[0922] 2-Chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-fluoropyridine (200 mg, 0.81 mmol) was dissolved in anhydrous dimethylformamide (8.0 mL) and then tert-butyl N-methyl-N-[(3S)-3-piperidyl]carbamate (173.1 mg, 0.81 mmol) and diisopropylethylamine (0.33 mL, 2.42 mmol) were added dropwise thereto. The reaction mixture was stirred at 80℃ overnight. Water was added to the reaction mixture and then the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (208.6 mg). (Yield: 58.4%) 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 2H), 7.97 (s, 1H), 7.41-7.11 (m, 1H), 6.91 (s, 1H), 3.28-3.22 (m, 2H), 2.79 (s, 3H), 2.75-2.71 (m, 1H), 2.43-2.31 (m, 1H), 1.89-1.88 (m, 1H), 1.74-1.73 (m, 1H), 1.63-1.59 (m, 2H), 1.48 (s, 9H)

[0923] Preparation B1-2: tert-butyl (R)-(1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)(methyl)carbamate

[0924] The titled compound was prepared in accordance with the same procedures as in Preparation B1-1, changing the amine reagent to tert-butyl N-methyl-N-[(3R)-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.16 (s, 2H), 7.97 (s, 1H), 7.42-7.11 (m, 1H), 6.91 (s, 1H), 3.29-3.25 (m, 2H), 2.79 (s, 3H), 2.74-2.71 (m, 1H), 2.45-2.43 (m, 1H), 1.90-1.89 (m, 1H), 1.88-1.74 (m, 1H), 1.72-1.64 (m, 2H), 1.48 (s, 9H)

[0925] Preparation B1-3: tert-butyl((3S,4R)-1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-methylpiperidin-3-yl)carbamate

[0926] The titled compound was prepared in accordance with the same procedures as in Preparation B1-1, changing the amine reagent to tert-butyl N-[(3S,4R)-4-methyl-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 8.12 (s, 1H), 7.96 (s, 1H), 7.27 (t, 1H), 6.91 (s, 1H), 4.36-4.33 (m, 1H), 3.53 (d, 1H), 3.40-3.31 (m, 1H), 3.23 (d, 1H), 2.52 (t, 1H), 2.38 (t, 1H), 1.73-1.70 (m, 1H), 1.46 (s, 9H), 1.40-1.30 (m, 2H), 1.07 (d, 3H)

[0927] Preparation B1-4: tert-butyl ((3S,5S)-1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-5-methylpiperidin-3-yl)carbamate

[0928] The titled compound was prepared in accordance with the same procedures as in Preparation B1-1, changing the amine reagent to tert-butyl N-[(3S,5S)-5-methyl-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 8.06 (s, 1H), 7.91 (s, 1H), 7.28 (t, 1H), 6.91 (s, 1H), 7.44 (brs, 1H), 3.97-3.89 (m, 1H), 3.19-3.09 (m, 2H), 2.97-2.93 (m, 1H), 2.27-2.22 (m, 1H), 1.86-1.83 (m, 2H), 1.46 (s, 9H), 1.35-1.27 (m, 1H), 0.82 (d, 3H)

[0929] Preparation B1-5: tert-butyl (S)-(1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-3-methylpiperidin-3-yl)carbamate

[0930] The titled compound was prepared in accordance with the same procedures as in Preparation B1-1, changing the amine reagent to tert-butyl N-[(3S)-3-methyl-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.19 (s, 1H), 8.16 (s, 1H), 7.94 (s, 1H), 7.27 (t, 1H), 6.90 (s, 1H), 4.59 (brs, 1H), 3.50 (d, 1H), 3.11 (d, 1H), 2.55-2.49 (m, 1H), 2.17-2.14 (m, 1H), 1.69-1.60 (m, 1H), 1.50-1.39 (m, 13H), 1.35-1.31 (m, 2H)

[0931] Preparation B1-6: tert-butyl ((3R,4S)-1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-fluoropiperidin-3-yl)carbamate

[0932] The titled compound was prepared in accordance with the same procedures as in Preparation B1-1, changing the amine reagent to tert-butyl N-[(3R,4S)-4-fluoro-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.17 (s, 1H), 8.13 (s, 1H), 7.95 (s, 1H), 7.27 (t, 1H), 6.95 (s, 1H), 4.95 (brs, 1H), 4.89 (d, 1H), 3.94-3.87 (m, 1H), 3.34-3.30 (m, 1H), 3.10-3.05 (m, 1H), 2.85-2.80 (m, 2H), 2.07-2.01 (m, 1H), 1.90-1.73 (m, 1H), 1.47 (s, 9H)

[0933] Preparation B1-7: tert-butyl ((3R,4R)-1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-fluoropiperidin-3-yl)carbamate

[0934] The titled compound was prepared in accordance with the same procedures as in Preparation B1-1, changing the amine reagent to tert-butyl N-[(3R,4R)-4-fluoro-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.18 (s, 1H), 8.11 (s, 1H), 7.95 (s, 1H), 7.28 (t, 1H), 6.95 (s, 1H), 4.70 (brs, 1H), 4.63-4.47 (m, 1H), 3.90-3.82 (m, 1H), 3.57-3.54 (m, 1H), 3.14-3.07 (m, 1H), 2.80-2.77 (m, 2H), 2.09-1.99 (m, 1H), 1.88-1.83 (m, 1H), 1.47 (s, 9H)

[0935] Preparation B1-8: tert-butyl ((3R,4R)-1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-hydroxypiperidin-3-yl)carbamate

[0936] The titled compound was prepared in accordance with the same procedures as in Preparation B1-1, changing the amine reagent to tert-butyl N-[(3R,4R)-4-hydroxy-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.17 (s, 1H), 8.14 (s, 1H), 7.96 (s, 1H), 7.27 (t, 1H), 6.93 (s, 1H), 4.68-4.67 (m, 1H), 3.61-3.54 (m, 3H), 3.25 (d, 1H), 2.73-2.64 (m, 2H), 2.56 (t, 1H), 2.03-1.99 (m, 1H), 1.47 (s, 9H)

[0937] Preparation B1-9: tert-butyl N-[(3R,4R)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-3-hydroxy-4-piperidyl]carbamate

[0938] The titled compound was prepared in accordance with the same procedures as in Preparation B1-1, changing the amine reagent to tert-butyl N-[(3R,4R)-3-hydroxy-4-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.17 (s, 1H), 8.11 (s, 1H), 7.96 (s, 1H), 7.45-7.10 (m, 1H), 6.95 (s, 1H), 4.75-4.60 (m, 1H), 4.05-3.95 (m, 1H), 3.60-3.40 (m, 3H), 3.30-3.20 (m, 1H), 2.67 (t, 1H), 2.57 (t, 1H), 2.00-1.90 (m, 1H), 1.49 (s, 9H)

[0939] Preparation B1-10: tert-butyl N-[(3R,4S)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-3-methyl-4-piperidyl]carbamate

[0940] The titled compound was prepared in accordance with the same procedures as in Preparation B1-1, changing the amine reagent to tert-butyl N-[(3R,4S)-3-methyl-4-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 8.12 (s, 1H), 7.95 (s, 1H), 7.45-7.10 (m, 1H), 6.92 (s, 1H), 4.65-4.55 (m, 1H), 3.90-3.80 (m, 1H), 3.05-2.90 (m, 2H), 2.90-2.75 (m, 2H), 2.25-2.15 (m, 1H), 1.75-1.65 (m, 1H), 1.46 (s, 9H), 0.94 (d, 3H)

[0941] Preparation B2-1: 1-(2-chloro-5-iodopyridin-4-yl)-N,N-dimethylpyrrolidin-3-amine

[0942] 2-chloro-4-fluoro-5-iodopyridine (200 mg, 0.78 mmol) was dissolved in anhydrous dimethylformamide (5.0 mL) and then 3-(dimethylamino)pyrrolidine (88.7 mg, 0.77 mmol) and diisopropylethylamine (0.32 mL, 2.33 mmol) were added dropwise thereto. The reaction mixture was stirred at 50℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (800 mg). (Yield: 60.8%) 1H NMR (CDCl3, 400MHz) δ 8.42 (s, 1H), 6.44 (s, 1H), 3.80-3.70 (m, 1H), 3.70-3.65 (m, 2H), 3.60 (t, 1H), 2.76-2.68 (m, 1H), 2.32 (s, 6H), 2.24-2.18 (m, 1H), 1.90-1.79 (m, 1H)

[0943] Preparation B2-2: (1-(2-chloro-5-iodopyridin-4-yl)-3-methylpyrrolidin-3-yl)methanol

[0944] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (3-methylpyrrolidin-3-yl)methanol. 1H NMR (CDCl3, 400MHz) δ 8.42 (s, 1H), 6.45 (s, 1H), 3.79-3.69 (m, 2H), 3.63 (d, 1H), 3.57 (d, 2H), 3.30 (d, 1H), 2.02-1.95 (m, 1H), 1.75-1.68 (m, 1H), 1.18 (s, 3H)

[0945] Preparation B2-3: 1-(1-(2-chloro-5-iodopyridin-4-yl)-4-fluoropiperidin-4-yl)-N,N-dimethylmethanamine

[0946] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to 1-(4-fluoro-4-piperidyl)-N,N-dimethyl-methanamine. 1H NMR (CDCl3, 400MHz) δ 8.56 (s, 1H), 6.88 (s, 1H), 3.37 (d, 2H), 3.07 (t, 2H), 2.55 (s, 1H), 2.49 (s, 1H), 2.35 (s, 6H), 2.10 (t, 2H), 1.95-1.75 (m, 2H)

[0947] Preparation B2-4: (1-(2-chloro-5-iodopyridin-4-yl)-4-(2,2-difluoroethyl)piperidin-4-yl)methanol

[0948] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to [4-(2,2-difluoroethyl)-4-piperidyl]methanol. 1H NMR (CDCl3, 400MHz) δ 8.55 (s, 1H), 6.86 (s, 1H), 6.29-5.98 (m, 1H), 3.69 (d, 2H), 3.21-3.09 (m, 4H), 2.12-2.01 (m, 2H), 1.83-1.74 (m, 4H), 1.60 (t, 1H)

[0949] Preparation B2-5: (S)-1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-carboxamide

[0950] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (3S)-piperidin-3-carboxamide. 1H NMR (CDCl3, 400MHz) δ 8.57 (s, 1H), 6.90 (s, 1H), 5.99 (s, 1H), 5.49 (s, 1H), 3.60-3.50 (m, 1H), 3.30-3.20 (m, 1H), 3.05-2.85 (m, 2H), 2.80-2.65 (m, 1H), 2.10-1.90 (m, 2H), 1.90-1.75 (m, 2H)

[0951] Preparation B2-6: (R)-1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-carboxamide

[0952] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (3R)-piperidin-3-carboxamide. 1H NMR (CDCl3, 400MHz) δ 8.58 (s, 1H), 6.90 (s, 1H), 5.98 (s, 1H), 5.43 (s, 1H), 3.60-3.50 (m, 1H), 3.30-3.20 (m, 1H), 3.05-2.85 (m, 2H), 2.75-2.65 (m, 1H), 2.10-1.90 (m, 2H), 1.90-1.75 (m, 2H)

[0953] Preparation B2-7: tert-butyl (R)-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)carbamate

[0954] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (R)-3-(tert-butoxycarbonylamino)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.56 (s, 1H), 6.84 (s, 1H), 4.92 (s, 1H), 3.93 (s, 1H), 3.40-3.25 (m, 1H), 3.15-2.95 (m, 2H), 2.95-2.80 (m, 1H), 2.00-1.70 (m, 3H), 1.65-1.50 (m, 1H), 1.46 (s, 9H)

[0955] Preparation B2-8: 2-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)-N,N-dimethylethan-1-amine

[0956] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to dimethyl[2-(piperidin-4-yl)ethyl]amine. 1H NMR (CDCl3, 400MHz) δ 8.53 (s, 1H), 6.81 (s, 1H), 3.53 (d, 2H), 2.71 (t, 2H), 2.33 (t, 2H), 2.24 (s, 6H), 1.84 (d, 2H), 1.51-1.43 (m, 5H)

[0957] Preparation B2-9: 1-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)cyclopropan-1-ol

[0958] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to 1-(piperidin-4-yl)cyclopropan-1-ol. 1H NMR (CDCl3, 400MHz) δ 8.55 (s, 1H), 6.83 (s, 1H), 3.64 (d, 2H), 2.69 (t, 2H), 1.90-1.70 (m, 5H), 1.25-1.15 (m, 1H), 0.80 (t, 2H), 0.55 (t, 2H)

[0959] Preparation B2-10: 1-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)ethan-1-ol

[0960] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to 1-(piperidin-4-yl)ethan-1-ol. 1H NMR (CDCl3, 400MHz) δ 8.54 (s, 1H), 6.83 (s, 1H), 3.71 (s, 1H), 3.70-3.64 (m, 1H), 3.61 (d, 2H), 2.69 (t, 2H), 2.02 (d, 1H), 1.78 (d, 1H), 1.65-1.40 (m, 2H), 1.39 (d, 1H), 1.26 (d, 3H)

[0961] Preparation B2-11: 2-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol

[0962] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to 2-methyl-2-(piperidin-4-yl)propan-1-ol. 1H NMR (CDCl3, 400MHz) δ 8.53 (s, 1H), 6.81 (s, 1H), 3.63 (d, 2H), 3.46 (d, 2H), 2.67 (t, 2H), 1.80 (d, 2H), 1.65-1.45 (m, 2H), 1.33 (t, 1H), 0.92 (s, 6H)

[0963] Preparation B2-12: 1-(2-chloro-5-iodopyridin-4-yl)-4-methylpiperazine

[0964] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to 1-methylpiperazine. 1H NMR (CDCl3, 400MHz) δ 8.55 (s, 1H), 6.84 (s, 1H), 3.21 (s, 4H), 2.64 (s, 4H), 2.38 (s, 3H)

[0965] Preparation B2-13: 2-chloro-5-iodo-4-(3-(2,2,2-trifluoroethyl)piperidin-1-yl)pyridine

[0966] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to 3-(2,2,2-trifluoroethyl)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.56 (s, 1H), 6.83 (s, 1H), 3.56 (d, 1H), 3.34 (d, 1H), 2.80 (t, 1H), 2.50 (t, 1H), 2.30-2.20 (m, 1H), 2.20-2.05 (m, 2H), 1.99 (d, 1H), 1.90-1.70 (m, 2H), 1.40-1.20 (m, 1H)

[0967] Preparation B2-14: 2-chloro-4-(3-(fluoromethyl)piperidin-1-yl)-5-iodopyridine

[0968] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to 3-(fluoromethyl)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.56 (s, 1H), 6.85 (s, 1H), 4.55-4.25 (m, 2H), 3.56 (d, 1H), 3.42 (d, 1H), 2.77 (t, 1H), 2.64 (t, 1H), 2.35-2.15 (m, 1H), 1.95-1.75 (m, 3H), 1.40-1.20 (m, 1H)

[0969] Preparation B2-15: N-(1-(2-chloro-5-iodopyridin-4-yl)piperidin-3-yl)acetamide

[0970] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to 3-acetamidopiperidine. 1H NMR (CDCl3, 400MHz) δ 8.59 (s, 1H), 6.87 (s, 1H), 6.04 (s, 1H), 4.35-4.25 (m, 1H), 3.25 (d, 1H), 3.20-3.10 (m, 1H), 3.05-2.95 (m, 2H), 2.03 (s, 3H), 2.00-1.85 (m, 1H), 1.85-1.65 (m, 3H)

[0971] Preparation B2-16: 2-chloro-5-iodo-4-(4-(trifluoromethyl)piperidin-1-yl)pyridine

[0972] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to 4-(trifluoromethyl)piperidine. 1H NMR (CDCl3, 400MHz) δ 8.58 (s, 1H), 6.85 (s, 1H), 3.63 (d, 2H), 2.73 (t, 2H), 2.35-2.20 (m, 1H), 2.10-2.00 (m, 2H), 1.95-1.80 (m, 2H)

[0973] Preparation B2-17: tert-butyl 8-(2-chloro-5-iodopyridin-4-yl)-2,8-diazaspiro[4.5]decan-2-carboxylate

[0974] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl 2,8-diazaspiro[4.5]decan-2-carboxylate. 1H NMR (CDCl3, 400MHz) δ 8.55 (s, 1H), 6.85 (d, 1H), 3.50-3.40 (m, 2H), 3.40-3.10 (m, 4H), 3.10-2.95 (m, 2H), 1.90-1.70 (m, 6H), 1.48 (s, 9H)

[0975] Preparation B2-18: tert-butyl 2-(2-chloro-5-iodopyridin-4-yl)-2,8-diazaspiro[4.5]decan-8-carboxylate

[0976] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl 2,8-diazaspiro[4.5]decan-8-carboxylate. 1H NMR (CDCl3, 400MHz) δ 8.42 (s, 1H), 6.44 (s, 1H), 3.72 (t, 2H), 3.55-3.45 (m, 4H), 3.45-3.35 (m, 2H), 1.87 (t, 2H), 1.65-1.50 (m, 4H), 1.48 (s, 9H)

[0977] Preparation B2-19: (3R,4R)-1-(2-chloro-5-iodopyridin-4-yl)-4-fluoropiperidin-3-ol

[0978] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl (3R,4R)-4-fluoropiperidin-3-ol. 1H NMR (CDCl3, 400MHz) δ 8.60 (s, 1H), 6.92 (s, 1H), 4.70-4.50 (m, 1H), 4.10-4.00 (m, 1H), 3.51 (d, 1H), 3.35-3.20 (m, 1H), 3.10-3.00 (m, 2H), 2.60 (d, 1H), 2.40-2.25 (m, 1H), 2.10-2.00 (m, 1H)

[0979] Preparation B2-20: (3R,4R)-1-(2-chloro-5-iodopyridin-4-yl)-4-(hydroxymethyl)piperidin-3-ol

[0980] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to trans-4-(hydroxymethyl)-3-piperidinol hydrochloride. 1H NMR (CDCl3, 400MHz) δ 8.56 (s, 1H), 6.86 (s, 1H), 3.95-3.85 (m, 2H), 3.85-3.75 (m, 1H), 3.68 (d, 1H), 3.51 (d, 1H), 3.32 (s, 1H), 2.74 (t, 1H), 2.59 (t, 1H), 2.24 (t, 1H), 1.85-1.70 (m, 2H), 1.55-1.40 (m, 1H)

[0981] Preparation B2-21: tert-butyl (R)-(1-(2-chloro-5-iodopyridin-4-yl)pyrrolidin-3-yl)carbamate

[0982] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (R)-3-(tert-butoxycarbonylamino)pyrrolidine. 1H NMR (CDCl3, 400MHz) δ 8.43 (s, 1H), 6.46 (s, 1H), 4.70 (s, 1H), 4.32 (s, 1H), 3.90-3.80 (m, 1H), 3.80 (q, 1H), 3.62 (q, 1H), 3.55-3.50 (m, 1H), 2.28-2.19 (m, 1H), 2.00-1.90 (m, 1H), 1.47 (s, 9H)

[0983] Preparation B2-22: tert-butyl (S)-(1-(2-chloro-5-iodopyridin-4-yl)pyrrolidin-3-yl)carbamate

[0984] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (S)-3-(tert-butoxycarbonylamino)pyrrolidine. 1H NMR (CDCl3, 400MHz) δ 8.43 (s, 1H), 6.46 (s, 1H), 4.71 (s, 1H), 4.32 (s, 1H), 3.90-3.85 (m, 1H), 3.78 (q, 1H), 3.62 (q, 1H), 3.55-3.50 (m, 1H), 2.28-2.19 (m, 1H), 2.00-1.90 (m, 1H), 1.47 (s, 9H)

[0985] Preparation B2-23: 8-(2-chloro-5-iodopyridin-4-yl)-2-methyl-2,8-diazaspiro[4.5]decane

[0986] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to 2-methyl-2,8-diazaspiro[4.5]decane. 1H NMR (CD3OD, 400MHz) δ 8.50 (s, 1H), 7.02 (d, 1H), 3.20-3.10 (m, 4H), 2.68 (t, 2H), 2.55 (s, 2H), 2.39 (s, 3H), 1.90-1.75 (m, 6H)

[0987] Preparation B2-24: (3S)-1-(2-chloro-5-iodo-4-pyridyl)-N-methyl-pyrrolidin-3-amine

[0988] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (S)-3-(methylamino)pyrrolidine. 1H NMR (CDCl3, 400MHz) δ 8.42 (s, 1H), 6.45 (s, 1H), 3.86-3.81 (m, 1H), 3.73 (q, 1H), 3.62 (q, 1H), 3.51-3.47 (m, 1H), 3.40-3.30 (m, 1H), 2.48 (s, 3H), 2.19-2.11 (m, 1H), 1.90-1.82 (m, 1H)

[0989] Preparation B2-25: (3S)-1-(2-chloro-5-iodo-4-pyridyl)-N-ethyl-pyrrolidin-3-amine

[0990] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (S)-3-(ethylamino)pyrrolidine. 1H NMR (CDCl3, 400MHz) δ 8.41 (s, 1H), 6.44 (s, 1H), 3.86-3.81 (m, 1H), 3.73-3.50 (m, 2H), 3.50-3.40 (m, 2H), 2.80-2.65 (m, 2H), 2.22-2.14 (m, 1H), 1.87-1.79 (m, 1H), 1.27 (t, 3H)

[0991] Preparation B2-26: (R)-N-(1-(2-chloro-5-iodopyridin-4-yl)pyrrolidin-3-yl)acetamide

[0992] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (R)-3-acetamidopyrrolidine. 1H NMR (CDCl3, 400MHz) δ 8.41 (s, 1H), 6.45 (s, 1H), 6.05-5.95 (m, 1H), 4.65-4.55 (m, 1H), 3.96-3.91 (m, 1H), 3.78 (q, 1H), 3.59-3.53 (m, 2H), 2.30-2.20 (m, 1H), 2.10-2.00 (m, 1H), 2.03 (s, 3H)

[0993] Preparation B2-27: (S)-N-(1-(2-chloro-5-iodopyridin-4-yl)pyrrolidin-3-yl)acetamide

[0994] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (S)-3-acetamidopyrrolidine. 1H NMR (CDCl3, 400MHz) δ 8.41 (s, 1H), 6.45 (s, 1H), 6.00-5.90 (m, 1H), 4.65-4.55 (m, 1H), 4.14-3.91 (m, 1H), 3.78 (q, 1H), 3.58-3.53 (m, 2H), 2.30-2.20 (m, 1H), 2.10-1.98 (m, 4H)

[0995] Preparation B2-28: 1-(2-chloro-5-iodo-4-pyridyl)piperidin-3-carboxamide

[0996] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to piperidin-3-carboxamide. 1H NMR (CDCl3, 400MHz) δ 8.58 (s, 1H), 6.90 (s, 1H), 5.98 (s, 1H), 5.41 (s, 1H), 3.56 (d, 1H), 3.30-3.20 (m, 1H), 3.10-2.90 (m, 2H), 2.75-2.65 (m, 1H), 2.10-1.90 (m, 2H), 1.90-1.75 (m, 2H)

[0997] Preparation B2-29: (1S,4S)-4-((2-chloro-5-iodopyridin-4-yl)(methyl)amino)cyclohexan-1-ol

[0998] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to cis-4-(methylamino)cyclohexanol. 1H NMR (CDCl3, 400MHz) δ 8.55 (s, 1H), 6.82 (s, 1H), 4.08 (brs, 1H), 3.59-3.53 (m, 1H), 2.80 (s, 3H), 2.05-2.00 (m, 2H), 1.92-1.88 (m, 2H), 1.65-1.57 (m, 4H), 1.27-1.27 (m, 1H)

[0999] Preparation B2-30: tert-butyl N-[(3S,6R)-1-(2-chloro-5-iodo-4-pyridyl)-6-methyl-3-piperidyl]carbamate

[1000] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3S,6R)-6-methyl-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.71 (s, 1H), 7.00 (s, 1H), 5.20 (s, 1H), 3.94 (s, 1H), 3.73 (s, 1H), 3.11-2.89 (m, 2H), 2.04-1.87 (m, 1H), 1.87-1.63 (m, 3H), 1.54 (s, 9H), 1.08 (d, 3H)

[1001] Preparation B2-31: tert-butyl N-[(3R,4S)-1-(2-chloro-5-iodo-4-pyridyl)-4-methoxy-3-piperidyl]carbamate

[1002] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3R,4S)-4-methoxy-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.62 (s, 1H), 6.92 (s, 1H), 5.27 (d, 1H), 4.11-3.98 (m, 1H), 3.64-3.52 (m, 1H), 3.48 (s, 3H), 3.34-3.25 (m, 1H), 3.23-3.12 (m, 1H), 3.07-2.93 (m, 2H), 2.19-2.08 (m, 1H), 1.97-1.81 (m, 1H), 1.56 (s, 9H)

[1003] Preparation B2-32: tert-butyl N-[(3R,4R)-1-(2-chloro-5-iodo-4-pyridyl)-4-methoxy-3-piperidyl]carbamate

[1004] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3R,4R)-4-methoxypiperidin-3-yl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.66 (s, 1H), 6.96 (s, 1H), 5.38 (s, 1H), 4.05 (s, 1H), 3.50 (s, 3H), 3.45-3.38 (m, 2H), 3.16-3.02 (m, 3H), 2.25-2.08 (m, 1H), 1.95-1.83 (m, 1H), 1.55 (s, 9H)

[1005] Preparation B2-33: tert-butyl N-methyl-N-[[(3R)-1-(2-chloro-5-iodo-4-pyridyl)-3-piperidyl]methyl]carbamate

[1006] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-methyl-N-([(3R)-piperidin-3-yl]methyl)carbamate. 1H NMR (CDCl3, 400MHz) δ 8.55 (s, 1H), 6.82 (s, 1H), 3.55-3.45 (m, 1H), 3.45-3.35 (m, 1H), 3.35-3.15 (m, 1H), 3.15-3.05 (m, 1H), 2.91 (s, 3H), 2.80-2.65 (m, 1H), 2.55-2.40 (m, 1H), 2.25-2.10 (m, 1H), 1.95-1.70 (m, 3H), 1.48 (s, 9H), 1.25-1.10 (m, 1H)

[1007] Preparation B2-34: tert-butyl N-methyl-N-[[(3S)-1-(2-chloro-5-iodo-4-pyridyl)-3-piperidyl]methyl]carbamate

[1008] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-methyl-N-([(3S)-piperidin-3-yl]methyl)carbamate. 1H NMR (CDCl3, 400MHz) δ 8.54 (s, 1H), 6.82 (s, 1H), 3.55-3.45 (m, 1H), 3.45-3.35 (m, 1H), 3.35-3.20 (m, 1H), 3.20-3.05 (m, 1H), 2.90 (s, 3H), 2.85-2.65 (m, 1H), 2.50-2.40 (m, 1H), 2.25-2.10 (m, 1H), 1.95-1.70 (m, 3H), 1.48 (s, 9H), 1.25-1.10 (m, 1H)

[1009] Preparation B2-35: tert-butyl N-[(3R,4R)-1-(2-chloro-5-iodo-4-pyridyl)-3-methyl-4-piperidyl]carbamate

[1010] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3R,4R)-3-methyl-4-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.55 (s, 1H), 6.84 (s, 1H), 4.50-4.40 (m, 1H), 3.60-3.50 (m, 2H), 2.85-2.75 (m, 1H), 2.55-2.45 (m, 1H), 2.20-2.10 (m, 1H), 1.85-1.70 (m, 1H), 1.49 (s, 9H), 1.04 (d, 3H)

[1011] Preparation B2-36: 2-chloro-5-iodo-4-[(3S)-3-methyl-1-piperidyl]pyridine

[1012] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (3S)-3-methylpiperidine. 1H NMR (CDCl3, 400MHz) δ 12.40 (s, 1H), 10.90 (s, 1H), 7.50-7.40 (m, 2H), 6.69 (t, 1H), 6.33 (t, 1H), 5.90-5.70 (m, 4H), 5.20-5.10 (m, 1H), 4.92 (d, 3H)

[1013] Preparation B2-37: 2-chloro-5-iodo-4-[(3S)-3-(fluoromethyl)-1-piperidyl]pyridine

[1014] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (3S)-3-(fluoromethyl)piperidine hydrochloride. 1H NMR (CDCl3, 400MHz) δ 12.50 (s, 1H), 11.00 (s, 1H), 8.45-8.35 (m, 1H), 8.35-8.20 (m, 1H), 7.60-7.50 (m, 1H), 7.45-7.35 (m, 1H), 6.78 (t, 1H), 6.60 (t, 1H), 6.25-6.10 (m, 1H), 5.90-5.70 (m, 3H), 5.35-5.20 (m, 1H)

[1015] Preparation B2-38: 2-chloro-5-iodo-4-[(3R)-3-(difluoromethyl)-1-piperidyl]pyridine

[1016] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to (3R)-3-(difluoromethyl)piperidine hydrochloride. 1H NMR (CDCl3, 400MHz) δ 12.50 (s, 1H), 11.00 (s, 1H), 10.00-9.60 (m, 1H), 7.65-7.50 (m, 1H), 7.40-7.30 (m, 1H), 6.78 (t, 1H), 6.68 (t, 1H), 6.30-6.15 (m, 1H), 6.00-5.80 (m, 2H), 5.80-5.65 (m, 1H), 5.50-5.35 (m, 1H)

[1017] Preparation B2-39: tert-butyl N-[(3S,4S)-1-(2-chloro-5-iodo-4-pyridyl)-3-fluoro-4-piperidyl]carbamate

[1018] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3S,4S)-3-fluoro-4-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.34 (s, 1H), 6.60 (s, 1H), 4.85-4.70 (m, 1H), 4.50-4.30 (m, 1H), 4.05-3.90 (m, 1H), 3.70-3.60 (m, 1H), 3.20-3.05 (m, 1H), 2.20-2.10 (m, 1H), 1.65-1.55 (m, 1H), 1.51 (s, 9H), 1.30-1.20 (m, 1H)

[1019] Preparation B2-40: tert-butyl N-[(3R,4S)-1-(2-chloro-5-iodo-4-pyridyl)-3-fluoro-4-piperidyl]carbamate

[1020] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3R,4S)-3-fluoro-4-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.58 (s, 1H), 6.88 (s, 1H), 5.00-4.90 (m, 1H), 4.90-4.70 (m, 1H), 3.95-3.75 (m, 1H), 3.75-3.65 (m, 1H), 3.20-3.00 (m, 1H), 2.87 (t, 1H), 2.20-2.00 (m, 1H), 1.95-1.85 (m, 1H), 1.49 (s, 9H)

[1021] Preparation B2-41: tert-butyl N-[(3S,4R)-1-(2-chloro-5-iodo-4-pyridyl)-3-fluoro-4-piperidyl]carbamate

[1022] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3S,4R)-3-fluoro-4-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.58 (s, 1H), 6.88 (s, 1H), 5.00-4.90 (m, 1H), 4.90-4.75 (m, 1H), 3.95-3.75 (m, 1H), 3.75-3.60 (m, 1H), 3.20-3.00 (m, 1H), 2.87 (t, 1H), 2.20-2.00 (m, 1H), 1.95-1.85 (m, 1H), 1.49 (s, 9H)

[1023] Preparation B2-42: tert-butyl N-[(3S,5R)-1-(2-chloro-5-iodo-4-pyridyl)-5-fluoro-3-piperidyl]carbamate

[1024] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3S,5R)-5-fluoro-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.68 (s, 1H), 6.98 (s, 1H), 5.28-5.08 (m, 1H), 5.07-4.84 (m, 1H), 4.16-3.98 (m, 1H), 3.45-3.28 (m, 2H), 3.28-3.11 (m, 2H), 2.32-2.13 (m, 1H), 2.07-1.87 (m, 1H), 1.64-1.54 (m, 1H), 1.54 (s, 9H)

[1025] Preparation B2-43: tert-butyl N-[(3S,5S)-1-(2-chloro-5-iodo-4-pyridyl)-5-fluoro-3-piperidyl]carbamate

[1026] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3S,5S)-5-fluoro-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.65 (s, 1H), 6.98 (s, 1H), 5.10-5.00 (m, 1H), 4.98-4.90 (m, 1H), 4.90-4.80 (m, 1H), 4.31-4.18 (m, 1H), 3.49-3.35 (m, 2H), 3.30-3.15 (m, 1H), 3.05-2.92 (m, 1H), 2.15-2.01 (m, 2H), 1.54 (s, 9H)

[1027] Preparation B2-44: tert-butyl N-[(3S,5R)-1-(2-chloro-5-iodo-4-pyridyl)-5-(trifluoromethyl)-3-piperidyl]carbamate

[1028] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3S,5R)-5-(trifluoromethyl)-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.66 (s, 1H), 6.93 (s, 1H), 4.59-4.39 (m, 1H), 4.04-3.85 (m, 1H), 3.81-3.65 (m, 2H), 2.86-2.69 (m, 1H), 2.69-2.56 (m, 1H), 2.52-2.33 (m, 2H), 1.54 (s, 9H)

[1029] Preparation B2-45: tert-butyl N-[(3S,5S)-1-(2-chloro-5-iodo-4-pyridyl)-5-hydroxy-3-piperidyl]carbamate

[1030] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3S,5S)-5-hydroxy-3-piperidyl]carbamate. 1H NMR (CDCl3, 400MHz) δ 8.65 (s, 1H), 6.96 (s, 1H), 5.33-5.13 (m, 1H), 4.22-4.07 (m, 1H), 4.05-3.89 (m, 1H), 3.43-3.27 (m, 2H), 3.07-2.95 (m, 2H), 2.24-2.14 (m, 1H), 2.14-2.06 (m, 1H), 1.70-1.61 (m, 1H), 1.53 (s, 9H)

[1031] Preparation B2-46: tert-butyl N-[(3R,4R)-1-(2-chloro-5-iodo-4-pyridyl)-3-hydroxy-4-piperidyl]carbamate

[1032] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl ((3R,4R)-3-hydroxypiperidin-4-yl)carbamate. 1H NMR (CDCl3, 400MHz) δ 8.58 (s, 1H), 6.89 (s, 1H), 4.80-4.65 (m, 1H), 4.10-3.95 (m, 1H), 3.80-3.65 (m, 2H), 3.60-3.45 (m, 2H), 2.82 (t, 1H), 2.66 (t, 1H), 2.20-2.05 (m, 1H), 1.80-1.65 (m, 1H), 1.50 (s, 9H)

[1033] Preparation B2-47: tert-butyl ((3R,4R)-1-(2-chloro-5-iodopyridin-4-yl)-4-fluoropiperidin-3-yl)carbamate

[1034] The titled compound was prepared in accordance with the same procedures as in Preparation B2-1, changing the amine reagent to tert-butyl N-[(3R,4R)-4-fluoropiperidin-3-yl]carbamate. 1H NMR (CDCl3, 400MHz) 8.68 (s, 1H), 7.00 (s, 1H), 5.31-5.03 (m, 1H), 4.86-4.72 (m, 0.5H), 4.74-4.59 (m, 0.5H), 4.20-3.87 (m, 1H), 3.52-3.32 (m, 1H), 3.25-3.02 (m, 3H), 2.41-2.16 (m, 1H), 2.16-1.96 (m, 1H), 1.48 (s, 9H)

[1035] Preparation B3-1: 1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-N,N-dimethylpyrrolidin-3-amine

[1036] 1-(2-chloro-5-iodopyridin-4-yl)-N,N-dimethylpyrrolidin-3-amine (the B2-1 intermediate, 44.2 mg, 0.13 mmol) was dissolved in anhydrous 1,4-dioxane (1.5 mL) and then 1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-boronic acid pinacol ester (35.0 mg, 0.13 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (5.1 mg, 0.006 mmol), and 2.0M sodium carbonate solution (0.3 mL, 0.6 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 80℃ overnight. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (24.4 mg). (Yield: 51.6%) 1H NMR (CDCl3, 400MHz) δ 7.87 (s, 1H), 7.52 (s, 1H), 7.43 (s, 1H), 6.53 (s, 1H), 4.42-4.33 (m, 1H), 4.13 (d, 2H), 3.57 (t, 2H), 3.26-3.14 (m, 3H), 2.95 (t, 1H), 2.64-3.32 (m, 1H), 2.19 (s, 6H), 2.15-2.00 (m, 5H), 1.80-1.65 (m, 1H)

[1037] Preparation B3-2: (1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-3-methylpyrrolidin-3-yl)methanol

[1038] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-2 intermediate. 1H NMR (CDCl3, 400MHz) δ 7.87 (s, 1H), 7.51 (s, 1H), 7.44 (s, 1H), 6.55 (s, 1H), 4.43-4.35 (m, 1H), 4.14 (d, 2H), 3.58 (t, 2H), 3.46 (d, 2H), 3.15 (t, 2H), 3.11 (d, 1H), 2.79 (d, 1H), 2.20-2.00 (m, 4H), 1.88-1.80 (m, 1H), 1.62-1.55 (m, 2H), 1.55-1.50 (m, 1H), 1.08 (s, 3H)

[1039] Preparation B3-3: 1-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-fluoropiperidin-4-yl)-N,N-dimethylmethanamine

[1040] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-3 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.85 (s, 1H), 7.74 (s, 1H), 6.90 (s, 1H), 4.44-4.38 (m, 1H), 4.15 (d, 2H), 3.56 (t, 2H), 3.15 (d, 2H), 2.95 (t, 2H), 2.50 (s, 1H), 2.44 (s, 1H), 2.32 (s, 6H), 2.30-2.24 (m, 1H), 2.20-2.10 (m, 4H), 2.00-1.90 (m, 2H), 1.70-1.60 (m, 1H)

[1041] Preparation B3-4: (1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-(2,2-difluoroethyl)piperidin-4-yl)methanol

[1042] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-4 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.84 (s, 1H), 7.76 (s, 1H), 6.88 (s, 1H), 6.24-5.93 (m, 1H), 4.44-4.37 (m, 1H), 4.15 (d, 2H), 3.64 (d, 2H), 3.58 (t, 2H), 3.05-2.90 (m, 4H), 2.20-1.95 (m, 7H), 1.65-1.55 (m, 4H), 1.27 (t, 1H)

[1043] Preparation B3-5: (S)-1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-carboxamide

[1044] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-5 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.83 (s, 1H), 7.75 (s, 1H), 6.88 (s, 1H), 5.45-5.40 (m, 1H), 5.25-5.15 (m, 1H), 4.45-4.40 (m, 1H), 4.15 (d, 2H), 3.58 (t, 2H), 3.43 (d, 1H), 3.21 (d, 1H), 2.79 (t, 1H), 2.65 (t, 1H), 2.55-2.40 (m, 1H), 2.37 (t, 1H), 2.20-2.05 (m, 4H), 2.05-1.90 (m, 3H)

[1045] Preparation B3-6: (R)-1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-carboxamide

[1046] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-6 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.83 (s, 1H), 7.75 (s, 1H), 6.89 (s, 1H), 5.45-5.35 (m, 1H), 5.25-5.15 (m, 1H), 4.50-4.30 (m, 1H), 4.15 (d, 2H), 3.58 (t, 2H), 3.43 (d, 1H), 3.22 (d, 1H), 2.79 (t, 1H), 2.66 (t, 1H), 2.50-2.40 (m, 1H), 2.20-2.05 (m, 4H), 2.05-1.90 (m, 1H), 1.85-1.75 (m, 1H), 1.75-1.60 (m, 1H)

[1047] Preparation B3-7: tert-butyl(R)-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[1048] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-7 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.81 (s, 1H), 7.77 (s, 1H), 6.86 (s, 1H), 4.55-4.45 (m, 1H), 4.45-4.35 (m, 1H), 4.15 (d, 2H), 3.80-3.70 (m, 1H), 3.58 (t, 2H), 3.43 (d, 1H), 3.07 (d, 1H), 2.65-2.55 (m, 1H), 2.55-2.45 (m, 1H), 2.25-2.05 (m, 4H), 2.00-1.90 (m, 1H), 1.75-1.65 (m, 1H), 1.45 (s, 9H), 1.40-1.30 (m, 1H)

[1049] Preparation B3-8: 2-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)-N,N-dimethylethan-1-amine

[1050] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-8 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.11 (s, 1H), 7.84 (s, 1H), 7.78 (s, 1H), 6.84 (s, 1H), 4.44-4.38 (m, 1H), 4.15 (d, 2H), 3.59 (t, 2H), 3.32 (d, 2H), 2.57 (t, 2H), 2.40-2.30 (m, 2H), 2.27 (s, 6H), 2.20-2.00 (m, 4H), 1.73 (d, 2H), 1.50-1.40 (m, 4H), 1.30-1.20 (m, 1H)

[1051] Preparation B3-9: 1-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)cyclopropan-1-ol

[1052] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-9 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.13 (s, 1H), 7.85 (s, 1H), 7.82 (s, 1H), 6.89 (s, 1H), 4.50-4.35 (m, 1H), 4.13 (d, 2H), 3.58 (t, 2H), 3.42 (d, 2H), 2.55 (t, 2H), 2.20-2.05 (m, 4H), 1.90-1.70 (m, 5H), 1.20-1.05 (m, 1H), 0.79 (t, 2H), 0.50 (t, 2H)

[1053] Preparation B3-10: 1-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol

[1054] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-10 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.84 (s, 1H), 7.79 (s, 1H), 6.86 (s, 1H), 4.44-4.35 (m, 1H), 4.14 (d, 2H), 3.65-3.50 (m, 4H), 3.45-3.35 (m, 2H), 2.56 (t, 2H), 2.20-2.05 (m, 4H), 1.90 (d, 1H), 1.65 (d, 1H), 1.45-1.35 (m, 2H), 1.35-1.25 (m, 1H), 1.21 (d, 3H)

[1055] Preparation B3-11: 2-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol

[1056] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-11 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.83 (s, 1H), 7.81 (s, 1H), 6.84 (s, 1H), 4.50-4.35 (m, 1H), 4.14 (d, 2H), 3.58 (t, 2H), 3.45-3.35 (m, 4H), 2.54 (t, 2H), 2.20-2.15 (m, 2H), 2.15-2.05 (m, 2H), 1.68 (d, 2H), 1.50-1.30 (m, 2H), 1.30-1.20 (m, 2H), 0.86 (s, 6H)

[1057] Preparation B3-12: 1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-methylpiperazine

[1058] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-12 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.13 (s, 1H), 7.84 (s, 1H), 7.78 (s, 1H), 6.86 (s, 1H), 4.45-4.35 (m, 1H), 4.16 (d, 2H), 3.59 (t, 2H), 3.01 (s, 4H), 2.47 (s, 4H), 2.33 (s, 3H), 2.20-2.05 (m, 4H)

[1059] Preparation B3-13: 2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-4-(3-(2,2,2-trifluoroethyl)piperidin-1-yl)pyridine

[1060] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-13 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 6.85 (s, 1H), 4.44-4.35 (m, 1H), 4.15 (d, 2H), 3.58 (t, 2H), 3.41 (d, 1H), 3.26 (d, 1H), 2.60 (t, 1H), 2.25 (t, 1H), 2.20-2.05 (m, 4H), 2.05-1.80 (m, 4H), 1.80-1.70 (m, 1H), 1.70-1.65 (m, 1H), 1.20-1.05 (m, 1H)

[1061] Preparation B3-14: 2-chloro-4-(3-(fluoromethyl)piperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridine

[1062] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-14 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.13 (s, 1H), 7.80 (s, 1H), 7.76 (s, 1H), 6.87 (s, 1H), 4.45-4.35 (m, 2H), 4.28-4.23 (m, 1H), 4.20-4.10 (m, 3H), 3.58 (t, 2H), 3.42 (d, 1H), 3.27 (d, 1H), 2.56 (t, 1H), 2.43 (t, 1H), 2.20-2.00 (m, 4H), 1.78 (t, 2H), 1.75-1.60 (m, 1H), 1.25-1.10 (m, 1H)

[1063] Preparation B3-15: N-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)acetamide

[1064] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-15 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.14 (s, 1H), 7.82-7.75 (m, 2H), 6.88 (s, 1H), 5.45-5.35 (m, 1H), 4.50-4.35 (m, 1H), 4.15 (d, 2H), 4.10-4.00 (m, 1H), 3.59 (t, 2H), 3.34 (d, 1H), 3.08 (d, 1H), 2.65 (t, 1H), 2.58 (t, 1H), 2.25-2.10 (m, 5H), 2.10-2.05 (m, 1H), 1.99 (s, 3H), 1.95-1.85 (m, 1H), 1.75-1.65 (m, 1H), 1.45-1.35 (m, 1H)

[1065] Preparation B3-16: 2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-4-(4-(trifluoromethyl)piperidin-1-yl)pyridine

[1066] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-16 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.83 (s, 1H), 7.78 (s, 1H), 6.87 (s, 1H), 4.50-4.35 (m, 1H), 4.15 (d, 2H), 3.59 (t, 2H), 3.43 (d, 2H), 2.67 (t, 2H), 2.20-2.05 (m, 5H), 1.91 (d, 2H), 1.70-1.55 (m, 2H)

[1067] Preparation B3-17: tert-butyl 8-[2-chloro-5-(1-tetrahydropyran-4-ylpyrazol-4-yl)-4-pyridyl]-2,8-diazaspiro[4.5]decan-2-carboxylate

[1068] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-17 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.86 (d, 1H), 7.76 (s, 1H), 6.87 (d, 1H), 4.45-4.35 (m, 1H), 4.15 (d, 2H), 3.59 (t, 2H), 3.45-3.30 (m, 2H), 3.25 (s, 1H), 3.17 (s, 1H), 3.05-2.95 (m, 2H), 2.95-2.80 (m, 2H), 2.16-2.05 (m, 4H), 1.80-1.70 (m, 2H), 1.65-1.50 (m, 4H), 1.47 (s, 9H)

[1069] Preparation B3-18: tert-butyl 2-[2-chloro-5-(1-tetrahydropyran-4-ylpyrazol-4-yl)-4-pyridyl]-2,8-diazaspiro[4.5]decan-8-carboxylate

[1070] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-18 intermediate. 1H NMR (CDCl3, 400MHz) δ 7.87 (s, 1H), 7.50 (s, 1H), 7.44 (s, 1H), 6.54 (s, 1H), 4.45-4.35 (m, 1H), 4.14 (d, 2H), 3.58 (t, 2H), 3.45-3.39 (m, 2H), 3.31-3.24 (m, 2H), 3.15 (t, 2H), 2.95 (s, 2H), 2.20-2.00 (m, 4H), 1.73 (t, 2H), 1.46 (s, 9H)

[1071] Preparation B3-19: (3R,4R)-1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-fluoropiperidin-3-ol

[1072] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-19 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.79 (s, 1H), 7.76 (s, 1H), 6.90 (s, 1H), 4.60-4.35 (m, 2H), 4.15 (d, 2H), 3.95-3.80 (m, 1H), 3.58 (t, 2H), 3.45-3.35 (m, 1H), 3.25-3.15 (m, 1H), 2.81-2.70 (m, 2H), 2.25-2.00 (m, 6H), 1.85-1.70 (m, 1H)

[1073] Preparation B3-20: (3R,4R)-1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-(hydroxymethyl)piperidin-3-ol

[1074] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-20 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.13 (s, 1H), 7.81 (s, 1H), 7.72 (s, 1H), 6.89 (s, 1H), 4.45-4.35 (m, 1H), 4.15 (d, 2H), 3.90-3.80 (m, 1H), 3.80-3.65 (m, 2H), 3.58 (t, 2H), 3.48 (d, 1H), 3.32 (d, 1H), 3.19 (s, 1H), 2.59 (t, 1H), 2.45 (t, 1H), 2.25-2.00 (m, 5H), 1.75-1.60 (m, 2H), 1.35-1.20 (m, 1H)

[1075] Preparation B3-21: tert-butyl (R)-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)pyrrolidin-3-yl)carbamate

[1076] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-21 intermediate. 1H NMR (CDCl3, 400MHz) δ 7.88 (s, 1H), 7.51 (s, 1H), 7.45 (s, 1H), 6.56 (s, 1H), 4.60-4.45 (m, 1H), 4.45-4.30 (m, 1H), 4.20-4.05 (m, 3H), 3.58 (t, 2H), 3.40-3.30 (m, 1H), 3.30-3.20 (m, 1H), 3.20-3.12 (m, 1H), 2.93-2.88 (m, 1H), 2.20-2.05 (m, 5H), 1.85-1.75 (m, 1H), 1.44 (s, 9H)

[1077] Preparation B3-22: tert-butyl (S)-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)pyrrolidin-3-yl)carbamate

[1078] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-22 intermediate. 1H NMR (CDCl3, 400MHz) δ 7.88 (s, 1H), 7.51 (s, 1H), 7.45 (s, 1H), 6.56 (s, 1H), 4.60-4.45 (m, 1H), 4.45-4.30 (m, 1H), 4.20-4.05 (m, 3H), 3.58 (t, 2H), 3.40-3.30 (m, 1H), 3.27-3.20 (m, 1H), 3.20-3.12 (m, 1H), 2.93-2.89 (m, 1H), 2.20-2.05 (m, 5H), 1.85-1.75 (m, 1H), 1.44 (s, 9H)

[1079] Preparation B3-23: 8-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-2-methyl-2,8-diazaspiro[4.5]decane

[1080] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-23 intermediate. 1H NMR (CDCl3, 400MHz) δ 8.11 (s, 1H), 8.08 (s, 1H), 7.89 (s, 1H), 7.02 (s, 1H), 4.55-4.45 (m, 1H), 4.09 (d, 2H), 3.60 (t, 2H), 3.55-3.40 (m, 2H), 3.05-2.95 (m, 2H), 2.70-2.65 (m, 2H), 2.57 (s, 1H), 2.45-2.35 (m, 4H), 2.20-2.00 (m, 4H), 1.85-1.75 (m, 2H), 1.75-1.60 (m, 4H)

[1081] Preparation B3-24: (3S)-1-[2-chloro-5-(1-tetrahydropyran-4-ylpyrazol-4-yl)-4-pyridyl]-N-methyl-pyrrolidin-3-amine

[1082] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-24 intermediate. 1H NMR (CD3OD, 400MHz) δ 7.81 (s, 1H), 7.76 (s, 1H), 7.56 (s, 1H), 6.69 (s, 1H), 4.50-4.40 (m, 1H), 4.08 (d, 2H), 3.59 (t, 2H), 3.35-3.25 (m, 2H), 3.25-3.10 (m, 2H), 2.99-2.94 (m, 1H), 2.39 (s, 3H), 2.20-2.00 (m, 6H), 1.80-1.70 (m, 1H)

[1083] Preparation B3-25: (3S)-1-[2-chloro-5-(1-tetrahydropyran-4-ylpyrazol-4-yl)-4-pyridyl]-N-ethyl-pyrrolidin-3-amine

[1084] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-25 intermediate. 1H NMR (CDCl3, 400MHz) δ 7.86 (s, 1H), 7.52 (s, 1H), 7.45 (s, 1H), 6.54 (s, 1H), 4.45-4.30 (m, 1H), 4.14 (d, 2H), 3.57 (t, 2H), 3.40-3.30 (m, 1H), 3.30-3.20 (m, 2H), 3.20-3.10 (m, 1H), 2.90-2.80 (m, 1H), 2.70-2.50 (m, 2H), 2.20-2.00 (m, 6H), 1.80-1.65 (m, 1H), 1.10 (t, 3H)

[1085] Preparation B3-26: (R)-N-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)pyrrolidin-3-yl)acetamide

[1086] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-26 intermediate. 1H NMR (CDCl3, 400MHz) δ 7.88 (s, 1H), 7.51 (s, 1H), 7.46 (s, 1H), 6.56 (s, 1H), 5.65-5.55 (m, 1H), 4.50-4.35 (m, 2H), 4.14 (d, 2H), 3.58 (t, 2H), 3.40-3.30 (m, 1H), 3.30-3.15 (m, 2H), 2.95-2.85 (m, 1H), 2.20-2.00 (m, 5H), 1.98 (s, 3H), 1.90-1.80 (m, 1H)

[1087] Preparation B3-27: (S)-N-(1-(2-chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)pyrrolidin-3-yl)acetamide

[1088] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-27 intermediate. 1H NMR (CDCl3, 400MHz) δ 7.87 (s, 1H), 7.51 (s, 1H), 7.46 (s, 1H), 6.56 (s, 1H), 5.65-5.55 (m, 1H), 4.50-4.30 (m, 2H), 4.15 (d, 2H), 3.58 (t, 2H), 3.40-3.30 (m, 1H), 3.30-3.10 (m, 2H), 2.95-2.85 (m, 1H), 2.20-2.00 (m, 5H), 1.97 (s, 3H), 1.90-1.80 (m, 1H)

[1089] Preparation B3-28: 8-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-2-methyl-2,8-diazaspiro[4.5]decane

[1090] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-23 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.17 (s, 1H), 8.15 (s, 1H), 8.03 (s, 1H), 7.45-7.05 (m, 1H), 6.91 (s, 1H), 2.93 (t, 4H), 2.57 (t, 2H), 2.41 (s, 2H), 2.32 (s, 3H), 1.71 (t, 4H), 1.69-1.62 (m, 2H)

[1091] Preparation B3-29: 8-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-2-methyl-2,8-diazaspiro[4.5]decane

[1092] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-23 intermediate and changing the boronic acid reagent to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.93 (s, 1H), 7.87 (s, 1H), 6.89 (s, 1H), 4.78 (q, 2H), 2.93 (t, 4H), 2.60 (t, 2H), 2.43 (s, 2H), 2.36 (s, 3H), 1.70 (t, 2H), 1.70-1.60 (m, 4H)

[1093] Preparation B3-30: 4-(6'-chloro-4'-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)-[3,3'-bipyridin]-6-yl)morpholine

[1094] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-23 intermediate and changing the boronic acid reagent to 6-(morpholin-4-yl)pyridin-3-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.35 (s, 1H), 7.99 (s, 1H), 7.76 (d, 1H), 6.85 (s, 1H), 6.72 (d, 1H), 3.88 (t, 4H), 3.58 (t, 4H), 2.94 (t, 4H), 2.57 (t, 2H), 2.44 (s, 2H), 2.33 (s, 3H), 1.65 (t, 2H), 1.65-1.45 (m, 4H)

[1095] Preparation B3-31: 2-(1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)-N,N-dimethylethan-1-amine

[1096] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-8 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.16 (s, 1H), 8.15 (s, 1H), 8.02 (s, 1H), 7.45-7.05 (m, 1H), 6.89 (s, 1H), 3.29 (d, 2H), 2.62 (t, 2H), 2.31 (t, 2H), 2.26 (s, 1H), 2.24 (s, 6H), 1.75 (d, 2H), 1.48 (t, 2H), 1.35-1.20 (m, 2H)

[1097] Preparation B3-32: 2-(1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)-N,N-dimethylethan-1-amine

[1098] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-8 intermediate and changing the boronic acid reagent to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.12 (s, 1H), 7.92 (s, 1H), 7.87 (s, 1H), 6.88 (s, 1H), 4.78 (q, 2H), 3.31 (d, 2H), 2.59 (t, 2H), 2.31 (t, 2H), 2.27 (s, 1H), 2.25 (s, 6H), 1.73 (d, 2H), 1.47 (t, 2H), 1.30-1.20 (m, 2H)

[1099] Preparation B3-33: 2-(1-(6-chloro-6'-morpholino-[3,3'-bipyridin]-4-yl)piperidin-4-yl)-N,N-dimethylethan-1-amine

[1100] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-8 intermediate and changing the boronic acid reagent to 6-(morpholin-4-yl)pyridin-3-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.34 (s, 1H), 7.98 (s, 1H), 7.76 (d, 1H), 6.84 (s, 1H), 6.72 (d, 1H), 3.88 (t, 4H), 3.59 (t, 4H), 3.34 (d, 2H), 2.59 (t, 2H), 2.30-2.25 (m, 3H), 2.23 (s, 6H), 1.66 (d, 2H), 1.43 (t, 2H), 1.25-1.10 (m, 2H)

[1101] Preparation B3-34: tert-butyl (R)-(1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)carbamate

[1102] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-7 intermediate and changing the boronic acid reagent to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 7.88 (s, 1H), 7.82 (s, 1H), 6.88 (s, 1H), 4.83-4.80 (m, 2H), 4.47-4.45 (m, 1H), 3.76-3.68 (m, 1H), 3.44-3.41 (m, 1H), 3.12-3.09 (m, 1H), 2.63-2.58 (m, 1H), 2.43-2.41 (m, 1H), 1.97-1.94 (m, 1H), 1.75-1.69 (m, 1H), 1.44 (s, 10H)

[1103] Preparation B3-35: (1S,4S)-4-((2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)(methyl)amino)cyclohexan-1-ol

[1104] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-29 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.04 (d, 2H), 7.86 (s, 1H), 7.26 (t, 1H), 6.86 (s, 1H), 3.96 (brs, 1H), 3.22-3.14 (m, 1H), 2.72 (s, 3H), 1.98-1.88 (m, 2H), 1.80 (d, 2H), 1.36-1.25 (m, 5H)

[1105] Preparation B3-36: tert-butyl N-[(3S,6R)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-6-methyl-3-piperidyl]carbamate

[1106] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-30 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.19 (s, 2H), 8.00 (s, 1H), 7.42-7.38 (m, 0.2H), 7.27-7.22 (m, 0.5H), 7.12-7.07 (m, 0.3H), 6.92-6.82 (m, 1H), 4.59-4.44 (m, 1H), 3.83-3.63 (m, 1H), 3.59-3.43 (m, 1H), 3.38-3.23 (m, 1H), 2.89-2.75 (m, 1H), 1.93-1.82 (m, 1H), 1.82-1.68 (m, 1H), 1.53 (s, 9H), 1.33-1.26 (m, 1H), 0.95 (d, 3H)

[1107] Preparation B3-37: tert-butyl N-[(3R,4S)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-4-methoxy-3-piperidyl]carbamate

[1108] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-31 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.18-8.09 (m, 2H), 7.99 (s, 1H), 7.44-7.40 (m, 0.2H), 7.28-7.26 (m, 0.6H), 7.13-7.11 (m, 0.2H), 6.97 (s, 1H), 5.12-5.01 (m, 1H), 3.91-3.76 (m, 1H), 3.59-3.51 (m, 1H), 3.41 (s, 3H), 3.25-3.14 (m, 1H), 3.00-2.85 (m, 2H), 2.85-2.74 (m, 1H), 2.01-1.89 (m, 1H), 1.52 (s, 9H)

[1109] Preparation B3-38: tert-butyl N-[(3R,4R)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-4-methoxy-3-piperidyl]carbamate

[1110] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-32 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.15 (s, 1H), 8.10 (s, 1H), 7.94 (s, 1H), 7.41-7.39 (m, 0.2H), 7.26-7.24 (m, 0.6H), 7.11-7.00 (m, 0.2H), 4.73-4.69 (m, 1H), 3.71-3.69 (m, 1H), 3.67-3.58 (m, 1H), 3.40 (s, 3H), 3.29-3.22 (m, 1H), 3.11-3.08 (m, 2H), 2.76-2.72 (m, 1H), 1.98-1.96 (m, 1H), 1.26 (s, 9H)

[1111] Preparation B3-39: tert-butyl (R)-((1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)methyl)(methyl)carbamate

[1112] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-33 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.20-8.05 (m, 2H), 8.00 (s, 1H), 7.45-7.10 (m, 1H), 6.89 (s, 1H), 3.30-3.10 (m, 3H), 3.10-2.90 (m, 1H), 2.80-2.70 (m, 3H), 2.59 (t, 1H), 2.45-2.25 (m, 1H), 2.00-1.85 (m, 1H), 1.85-1.70 (m, 2H), 1.65-1.50 (m, 1H), 1.48 (s, 9H), 1.15-1.00 (m, 1H)

[1113] Preparation B3-40: tert-butyl (S)-((1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)methyl)(methyl)carbamate

[1114] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-34 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.20-8.05 (m, 2H), 8.00 (s, 1H), 7.45-7.10 (m, 1H), 6.89 (s, 1H), 3.30-3.05 (m, 3H), 3.05-2.90 (m, 1H), 2.85-2.70 (m, 3H), 2.59 (t, 1H), 2.45-2.25 (m, 1H), 2.00-1.80 (m, 1H), 1.80-1.70 (m, 2H), 1.65-1.55 (m, 1H), 1.45 (s, 9H), 1.20-1.00 (m, 1H)

[1115] Preparation B3-41: tert-butyl ((3R,4R)-1-(2-chloro-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-3-methylpiperidin-4-yl)carbamate

[1116] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-35 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.20-8.10 (m, 2H), 7.98 (s, 1H), 7.45-7.10 (m, 1H), 7.11 (s, 1H), 4.45-4.35 (m, 1H), 3.35-3.20 (m, 3H), 2.69 (t, 1H), 2.40 (t, 1H), 2.05-1.95 (m, 1H), 1.55-1.50 (m, 1H), 1.47 (s, 9H), 0.93 (d, 3H)

[1117] Preparation B3-42: 2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-[(3S)-3-methyl-1-piperidyl]pyridine

[1118] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-36 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.17 (s, 1H), 8.15 (s, 1H), 7.99 (s, 1H), 7.45-7.10 (m, 1H), 6.90 (s, 1H), 3.30-3.15 (m, 2H), 2.60-2.50 (m, 1H), 2.30-2.20 (m, 1H), 1.90-1.80 (m, 1H), 1.80-1.65 (m, 2H), 1.65-1.50 (m, 1H), 1.10-1.00 (m, 1H), 0.87 (d, 3H)

[1119] Preparation B3-43: 2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-[(3S)-3-(fluoromethyl)-1-piperidyl]pyridine

[1120] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-37 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.16 (s, 1H), 8.15 (s, 1H), 7.98 (s, 1H), 7.45-7.10 (m, 1H), 6.93 (s, 1H), 4.45-4.10 (m, 2H), 3.45-3.35 (m, 1H), 3.30-3.15 (m, 1H), 2.59 (t, 1H), 2.52 (t, 1H), 2.15-2.00 (m, 1H), 1.85-1.70 (m, 2H), 1.70-1.55 (m, 1H), 1.30-1.10 (m, 1H)

[1121] Preparation B3-44: 2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-[(3R)-3-(difluoromethyl)-1-piperidyl]pyridine

[1122] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-38 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.18 (s, 1H), 8.14 (s, 1H), 7.97 (s, 1H), 7.45-7.10 (m, 1H), 6.93 (s, 1H), 5.80-5.45 (m, 1H), 3.45-3.35 (m, 1H), 3.30-3.20 (m, 1H), 2.65-2.55 (m, 2H), 2.20-2.00 (m, 1H), 2.00-1.90 (m, 1H), 1.85-1.75 (m, 1H), 1.65-1.50 (m, 1H), 1.45-1.30 (m, 1H)

[1123] Preparation B3-45: tert-butyl N-[(3S,4S)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-3-fluoro-4-piperidyl]carbamate

[1124] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-39 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 7.95 (s, 1H), 7.94 (s, 1H), 7.78 (s, 1H), 7.43-7.12 (m, 1H), 6.70 (s, 1H), 4.45-4.35 (m, 1H), 4.35-4.20 (m, 1H), 4.05-3.90 (m, 1H), 3.70-3.55 (m, 1H), 3.15-3.00 (m, 1H), 3.00-2.95 (m, 1H), 2.20-2.10 (m, 1H), 1.46 (s, 9H), 1.45-1.35 (m, 1H)

[1125] Preparation B3-46: tert-butyl N-[(3R,4S)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-3-fluoro-4-piperidyl]carbamate

[1126] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-40 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.25 (s, 1H), 8.21 (s, 1H), 8.00 (s, 1H), 7.41-7.10 (m, 1H), 6.93 (s, 1H), 4.95-4.85 (m, 1H), 4.85-4.70 (m, 1H), 3.87-3.70 (m, 1H), 3.70-3.60 (m, 1H), 3.35-3.25 (m, 1H), 3.00-2.80 (m, 1H), 2.80-2.70 (m, 1H), 1.90-1.80 (m, 1H), 1.48 (s, 9H)

[1127] Preparation B3-47: tert-butyl N-[(3S,4R)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-3-fluoro-4-piperidyl]carbamate

[1128] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-41 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.25 (s, 1H), 8.21 (s, 1H), 8.07 (s, 1H), 7.41-7.02 (m, 1H), 6.93 (s, 1H), 4.95-4.85 (m, 1H), 4.85-4.70 (m, 1H), 3.85-3.70 (m, 1H), 3.70-3.60 (m, 1H), 3.40-3.25 (m, 1H), 3.00-2.80 (m, 1H), 2.80-2.70 (m, 1H), 1.85-1.75 (m, 1H), 1.48 (s, 9H)

[1129] Preparation B3-48: tert-butyl N-[(3S,5R)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-5-fluoro-3-piperidyl]carbamate

[1130] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-42 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.23 (s, 1H), 8.15 (s, 1H), 7.94 (s, 1H), 7.43-7.39 (m, 0.2H), 7.28-7.25 (m, 0.6H), 7.13-7.10 (m, 0.2H), 7.03 (s, 1H), 5.12-4.97 (m, 1H), 4.84-4.74 (m, 0.5H), 4.72-4.62 (m, 0.5H), 4.03-3.87 (m, 1H), 3.31-3.19 (m, 1H), 3.19-3.10 (m, 2H), 3.07-2.91 (m, 1H), 2.20-2.10 (m, 0.5H), 2.10-2.03 (m, 0.5H), 2.03-1.88 (m, 1H), 1.51 (s, 9H)

[1131] Preparation B3-49: tert-butyl N-[(3S,5S)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-5-fluoro-3-piperidyl]carbamate

[1132] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-43 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.25 (s, 2H), 7.97 (s, 1H), 7.44-7.40 (m, 0.2H), 7.27-7.25 (m, 0.6H), 7.13-7.09 (m, 0.2H), 7.02 (s, 1H), 4.95-4.86 (m, 0.5H), 4.83-4.75 (m, 0.5H), 4.47-4.32 (m, 1H), 4.12-3.98 (m, 1H), 3.63-3.53 (m, 1H), 3.53-3.43 (m, 1H), 2.84-2.76 (m, 0.5H), 2.76-2.68 (m, 0.5H), 2.60-2.49 (m, 1H), 2.42-2.29 (m, 1H), 1.50 (s, 9H)

[1133] Preparation B3-50: tert-butyl N-[(3S,5R)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-5-(trifluoromethyl)-3-piperidyl]carbamate

[1134] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-44 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) 8.64 (s, 1H), 8.12 (s, 1H), 7.99 (s, 1H), 7.28-7.26 (m, 0.2H), 7.26-7.20 (m, 0.6H), 7.02-7.01 (m, 0.2H), 6.93-6.93 (m, 1H), 4.43-4.41 (m, 1H), 3.73-3.71 (m, 2H), 3.63-3.60 (m, 1H), 3.45-3.42 (m, 1H), 2.66-2.52 (m, 1H), 2.49-2.33 (m, 2H), 1.47 (s, 9H)

[1135] Preparation B3-51: tert-butyl N-[(3S,5S)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-5-hydroxy-3-piperidyl]carbamate

[1136] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-45 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.17-8.15 (m, 2H), 7.93 (s, 1H), 7.41-7.40 (m, 0.2H), 7.28-7.20 (m, 0.6H), 7.11-7.09 (m, 0.2H), 6.98 (s, 1H), 5.15-5.10 (m, 1H), 3.92-3.90 (m, 1H), 3.89-3.82 (m, 1H), 3.33-3.30 (m, 1H), 3.12-3.09 (m, 1H), 2.81-2.76 (m, 2H), 2.16-2.13 (m, 1H), 1.55-1.52 (m, 1H), 1.45 (s, 9H)

[1137] Preparation B3-52: tert-butyl N-[(3R,4R)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-3-hydroxy-4-piperidyl]carbamate

[1138] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-46 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.17 (s, 1H), 8.11 (s, 1H), 7.96 (s, 1H), 7.41-7.10 (m, 1H), 6.95 (s, 1H), 4.75-4.65 (m, 1H), 4.10-4.00 (m, 1H), 3.60-3.40 (m, 2H), 3.30-3.20 (m, 1H), 2.75-2.60 (m, 1H), 2.60-2.55 (m, 1H), 2.00-1.90 (m, 1H), 1.48 (s, 9H)

[1139] Preparation B3-53: (3R,4R)-1-[2-chloro-5-[1-(difluoromethyl)pyrazol-4-yl]-4-pyridyl]-4-fluoro-piperidin-3-ol

[1140] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-19 intermediate and changing the boronic acid reagent to 1-(difluoromethyl)pyrazol-4-boronic acid pinacol ester. 1H NMR (CDCl3, 400MHz) δ 8.20 (s, 1H), 8.18 (s, 1H), 7.98 (s, 1H), 7.42-7.12 (m, 1H), 6.96 (s, 1H), 4.60-4.40 (m, 1H), 3.95-3.85 (m, 1H), 3.45-3.35 (m, 1H), 3.25-3.15 (m, 1H), 2.85-2.75 (m, 1H), 2.30-2.20 (m, 1H), 2.20-2.10 (m, 1H), 1.90-1.75 (m, 1H)

[1141] Preparation B3-54: tert-butyl ((3S,5R)-1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-5-fluoropiperidin-3-yl)carbamate

[1142] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-42 intermediate and changing the boronic acid reagent to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.24 (s, 1H), 7.91 (s, 1H), 7.84 (s, 1H), 7.02 (s, 1H), 5.03-4.93 (m, 1H), 4.87-4.75 (m, 3H), 3.99-3.87 (m, 1H), 3.27-3.11 (m, 2H), 3.11-2.95 (m, 2H), 2.21-2.04 (m, 1H), 1.94-1.84 (m, 1H), 1.50 (s, 9H)

[1143] Preparation B3-55: tert-butyl ((3S,5S)-1-(2-chloro-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)-5-fluoropiperidin-3-yl)carbamate

[1144] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-43 intermediate and changing the boronic acid reagent to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.24 (s, 1H), 8.03 (s, 1H), 7.84 (s, 1H), 6.97 (s, 1H), 4.91-4.70 (m, 4H), 4.47-4.32 (m, 1H), 4.13-3.98 (m, 1H), 3.61-3.40 (m, 2H), 2.88-2.69 (m, 1H), 2.51-2.29 (m, 2H), 1.51 (s, 9H)

[1145] Preparation B3-56: tert-butyl N-[(3S,5R)-1-[2-chloro-5-(1-isopropylpyrazol-4-yl)-4-pyridyl]-5-fluoro-3-piperidyl]carbamate

[1146] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-42 intermediate and changing the boronic acid reagent to 1-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.25 (s, 1H), 7.83 (s, 1H), 7.75 (s, 1H), 6.98 (s, 1H), 5.14-4.99 (m, 1H), 4.81-4.72 (m, 0.5H), 4.69-4.63 (m, 0.5H), 4.63-4.51 (m, 1H), 4.05-3.92 (m, 1H), 3.33-3.23 (m, 1H), 3.23-3.14 (m, 1H), 3.14-3.05 (m, 1H), 3.01-2.80 (m, 1H), 2.19-2.06 (m, 0.5H), 2.06-1.89 (m, 1.5H), 1.60 (d, 6H), 1.51 (s, 9H)

[1147] Preparation B3-57: tert-butyl N-[(3S,5S)-1-[2-chloro-5-(1-isopropylpyrazol-4-yl)-4-pyridyl]-5-fluoro-3-piperidyl]carbamate

[1148] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-43 intermediate and changing the boronic acid reagent to 1-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.23 (s, 1H), 7.94 (s, 1H), 7.74 (s, 1H), 6.94 (s, 1H), 4.90-4.81 (m, 1H), 4.77-4.70 (m, 1H), 4.64-4.58 (m, 1H), 4.58-4.47 (m, 1H), 4.15-4.01 (m, 1H), 3.58-3.39 (m, 2H), 2.79-2.59 (m, 1H), 2.59-2.48 (m, 1H), 2.39-2.26 (m, 1H), 1.57 (d, 6H), 1.48 (s, 9H)

[1149] Preparation B3-58: tert-butyl N-[(3R,4R)-1-[2-chloro-5-(1-isopropylpyrazol-4-yl)-4-pyridyl]-4-fluoro-3-piperidyl]carbamate

[1150] The titled compound was prepared in accordance with the same procedures as in Preparation B3-1, using the B2-47 intermediate and changing the boronic acid reagent to 1-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.16 (s, 1H), 7.76 (s, 1H), 7.73 (s, 1H), 6.90 (s, 1H), 4.80-4.70 (m, 1H), 4.65-4.55 (m, 1H), 4.55-4.40 (m, 1H), 4.00-3.85 (m, 1H), 3.55-3.45 (m, 1H), 3.10-3.00 (m, 1H), 2.85-2.75 (m, 1H), 2.05-1.95 (m, 1H), 1.85-1.75 (m, 1H), 1.59 (d, 6H), 1.47 (s, 9H)

[1151] Preparation B4-1: 2-chloro-4-fluoro-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridine

[1152] 2-Chloro-4-fluoro-5-iodopyridine (1.0 g, 3.88 mmol) was dissolved in anhydrous 1,4-dioxane (10.00 mL) and then 4-ethynyl-tetrahydro-2H-pyrane (470.7 mg, 4.27 mmol), bis(triphenylphosphine)palladium(II) dichloride (129.8 mg, 0.18 mmol), copper(I) iodide (44.4 mg, 0.23 mmol), and triethylamine (1.0 mL, 7.77 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 80℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (799.6 mg). (Yield: 85.9%) 1H NMR (CDCl3, 400MHz) δ 8.41 (d, 1H), 7.11 (d, 1H), 3.95-3.92 (m, 2H), 3.58-3.53 (m, 2H), 2.93-2.89 (m, 1H), 1.95-1.91 (m, 2H), 1.81-1.74 (m, 2H)

[1153] Preparation B4-2: 2-chloro-4-fluoro-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridine

[1154] The titled compound was prepared in accordance with the same procedures as in Preparation B4-1, changing the ethyne reagent to 4-ethynyl-1-(trifluoromethyl)-1H-pyrazole. 1H NMR (CDCl3, 400MHz) δ 8.52 (d, 1H), 8.07 (s, 1H), 7.92 (s, 1H), 7.18 (d, 1H)

[1155] Preparation B5-1: 1-(2-chloro-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)azetidin-3-ol

[1156] 2-Chloro-4-fluoro-5-(2-tetrahydropyran-4-ylethynyl)pyridine (the B4-1 intermediate, 100 mg, 0.42 mmol) was dissolved in anhydrous dimethylformamide (2.0 mL) and then 3-hydroxyazetidine hydrochloride (50.3 mg, 0.46 mmol) and diisopropylethylamine (0.17 mL, 1.25 mmol) were added dropwise thereto. Then, the mixed solution was stirred at room temperature overnight. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (83.3 mg). (Yield: 68.2%) 1H NMR (CDCl3, 400MHz) δ 7.99 (s, 1H), 6.16 (s, 1H), 4.77-4.75 (m, 1H), 4.53-4.49 (m, 2H), 4.09-4.08 (m, 2H), 4.06-3.91 (m, 2H), 3.55-3.49 (m, 2H), 2.93-2.81 (m, 1H), 2.51-2.49 (m, 1H), 1.91-1.87 (m, 2H), 1.79-1.72 (m, 2H)

[1157] Preparation B5-2: (R)-1-(2-chloro-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol

[1158] The titled compound was prepared in accordance with the same procedures as in Preparation B5-1, using the B4-2 intermediate and changing the amine reagent to (R)-piperidin-3-ol. 1H NMR (CDCl3, 400MHz) δ 8.27 (s, 1H), 8.16 (s, 1H), 7.92 (s, 1H), 6.83 (s, 1H), 4.01-4.13 (m, 1H), 3.60-3.71 (m, 1H), 3.46-3.20 (m, 2H), 3.17-3.15 (m, 1H), 1.98-1.81 (m, 2H), 1.61-1.56 (m, 2H)

[1159] Preparation C1-1: 2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine

[1160] 2-bromo-4-pyrimidinamine (3.0 g, 17.24 mmol) was dissolved in anhydrous acetonitrile (86.2 mL) and then 2-fluoro-6-methoxyphenylboronic acid (4.4 g, 25.86 mmol), bis(triphenylphosphine)palladium(II) dichloride (605.0 mg, 0.86 mmol), and 2.0M sodium carbonate solution (25.8 mL, 51.72 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 100℃ overnight. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (1.2 g). (Yield: 31.7%) 1H NMR (CDCl3, 400MHz) δ 8.39 (d, 1H), 7.34-7.28 (m, 1H), 6.81-6.76 (m, 2H), 6.43 (d, 1H), 4.97 (brs, 2H), 3.81 (s, 3H)

[1161] Preparation C1-2: 5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-amine

[1162] The titled compound was prepared in accordance with the same procedures as in Preparation C1-1, changing the amine reagent to 6-chloro-5-fluoropyridin-2-amine. 1H NMR (CDCl3, 400MHz) δ 7.37-7.30 (m, 2H), 6.82-6.77 (m, 2H), 6.54-6.51 (m, 1H), 4.41 (brs, 2H), 3.81 (s, 3H)

[1163] Preparation C1-3: 5-chloro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-amine

[1164] The titled compound was prepared in accordance with the same procedures as in Preparation C1-1, changing the amine reagent to 6-bromo-5-chloro-pyridin-2-amine. 1H NMR (CDCl3, 400MHz) δ 7.52 (d, 1H), 7.37-7.33 (m, 1H), 6.82-6.77 (m, 2H), 6.50 (d, 1H), 4.52 (brs, 2H), 3.81 (s, 3H)

[1165] Preparation C1-4: 6-(2-fluoro-6-methoxyphenyl)-5-methylpyridin-2-amine

[1166] The titled compound was prepared in accordance with the same procedures as in Preparation C1-1, changing the amine reagent to 6-bromo-5-methyl-pyridin-2-amine. 1H NMR (CDCl3, 400MHz) δ 7.37 (d, 1H), 7.35-7.31 (m, 1H), 6.81-6.76 (m, 2H), 6.49 (d, 1H), 4.35 (brs, 2H), 3.78 (s, 3H), 1.99 (s, 3H)

[1167] Preparation C1-5: 6-(2-fluoro-6-methoxy-phenyl)-5-methylsulfonyl-pyridin-2-amine

[1168] The titled compound was prepared in accordance with the same procedures as in Preparation C1-1, changing the amine reagent to 6-bromo-5-(methylsulfonyl)pyridin-2-amine. 1H NMR (CDCl3, 400MHz) 8.17 (d, 1H), 7.40 (q, 1H), 6.85-6.79 (m, 2H), 6.61 (d, 1H), 5.06 (s, 2H), 3.81 (s, 3H), 2.84 (s, 3H)

[1169] Preparation C1-6: 2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-amine

[1170] The titled compound was prepared in accordance with the same procedures as in Preparation C1-1, changing the boronic acid reagent to (7-fluoroquinoxalin-6-yl)boronic acid. 1H NMR (CD3OD, 400MHz) 8.94-9.92 (m, 2H), 8.54 (d, 1H), 8.24 (d, 1H), 7.89 (d, 1H), 6.59 (d, 1H)

[1171] Preparation C1-7: 2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine

[1172] The titled compound was prepared in accordance with the same procedures as in Preparation C1-1, changing the boronic acid reagent to (2,4-difluoro-6-methoxy-phenyl)boronic acid. 1H NMR (CD3OD, 400MHz) 8.38 (d, 1H), 6.53-6.50 (m, 2H), 6.43 (d, 1H), 5.00 (brs, 2H), 3.78 (s, 3H)

[1173] Preparation C1-8: 6-(2-fluoro-6-methoxyphenyl)pyridin-2-amine

[1174] The titled compound was prepared in accordance with the same procedures as in Preparation C1-1, changing the amine reagent to 6-bromopyridin-2-amine. 1H NMR (CDCl3, 400MHz) δ 7.52 (t, 1H), 7.34-7.28 (m, 1H), 6.80-6.74 (m, 3H), 6.51 (d, 1H), 4.48 (brs, 2H), 3.79 (s, 3H)

[1175] Preparation C1-9: 2-(2-methoxypyridin-3-yl)pyrimidin-4-amine

[1176] The titled compound was prepared in accordance with the same procedures as in Preparation C1-1, changing the boronic acid reagent to 2-methoxy-3-pyridylboronic acid reagent. 1H NMR (CDCl3, 400MHz) 8.39 (d, 1H), 8.25 (s, 1H), 8.01 (d, 1H), 6.99 (t, 1H), 6.40 (d, 1H), 4.97 (s, 2H), 4.03 (s, 3H)

[1177] Preparation C1-10: methyl 4-(4-aminopyrimidin-2-yl)-3-fluoro-5-methoxybenzoate

[1178] The titled compound was prepared in accordance with the same procedures as in Preparation C1-1, changing the boronic acid reagent to (methyl 3-fluoro-5-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate. 1H NMR (CD3OD, 400MHz) 8.17 (d, 1H), 7.55 (s, 1H), 7.46 (d, 1H), 6.56 (d, 1H), 3.96 (s, 3H), 3.87 (s, 3H)

[1179] Preparation C1-11: [2-(4-aminopyrimidin-2-yl)-3-fluoro-phenyl]methanol

[1180] The titled compound was prepared in accordance with the same procedures as in Preparation C1-1, changing the boronic acid reagent to [2-fluoro-6-(hydroxymethyl)phenyl]boronic acid. 1H NMR (CD3OD, 400MHz) δ 8.22 (d, 1H), 7.53-7.43 (m, 1H), 7.43-7.38 (m, 1H), 7.18-7.11 (m, 1H), 6.60 (d, 1H), 4.54 (s, 2H)

[1181] Preparation C2-1: methyl 6-amino-2-(2-fluoro-6-methoxyphenyl)nicotinate

[1182] Methyl 6-amino-2-chloronicotinate (1.0 g, 5.36 mmol) was dissolved in anhydrous acetonitrile (30.0 mL) and then 2-fluoro-6-methoxyphenylboronic acid (1.82 g, 10.72 mmol), tetrakis(triphenylphosphine)palladium(0) (400.0 mg, 0.35 mmol), and potassium carbonate (2.22 g, 16.08 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 100℃ for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (1.1 g). (Yield: 78.5%) 1H NMR (CDCl3, 400MHz) δ 8.15 (d, 1H), 7.34-7.32 (m, 1H), 6.81-6.75 (m, 2H), 6.51 (d, 1H), 4.94 (brs, 2H), 3.76 (s, 3H), 3.66 (s, 3H)

[1183] Preparation C3-1: 6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-amine

[1184] 6-Chloro-5-nitro-pyridin-2-amine (1.0 g, 5.76 mmol) was dissolved in anhydrous acetonitrile (30.0 mL) and then 2-fluoro-6-methoxyphenylboronic acid (1.82 g, 10.72 mmol), tetrakis(triphenylphosphine)palladium(0) (400.0 mg, 0.35 mmol), and potassium carbonate (2.22 g, 16.08 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 100℃ for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (1.17 g). (Yield: 82.9%) 1H NMR (CDCl3, 400MHz) δ 8.30 (d, 1H), 7.39-7.35 (m, 1H), 6.83 (t, 1H), 6.77 (d, 1H), 6.54 (d, 1H), 5.22 (brs, 2H), 3.76 (s, 3H)

[1185] Preparation C3-2: 6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-amine

[1186] The titled compound was prepared in accordance with the same procedures as in Preparation C3-1, changing the boronic acid reagent to (2,4-difluoro-6-methoxy-phenyl)boronic acid. 1H NMR (CD3OD, 400MHz) 8.26 (d, 1H), 6.75 (d, 1H), 6.66-6.61 (m, 2H), 3.74 (s, 3H)

[1187] Preparation C4-1: 4-(4-aminopyrimidin-2-yl)-3-fluoro-5-methoxybenzaldehyde

[1188] 2-Bromopyrimidin-4-amine (1.9 g, 11.11 mmol) was dissolved in anhydrous acetonitrile (44.9 mL) and water (12.5 mL) and then (2-fluoro-4-formyl-6-methoxy-phenyl)boronic acid (2.0 g, 10.1 mmol), XPhos Pd G2 (794.9 mg, 1.01 mmol), and potassium phosphate tribasic (6.4 g, 30.31 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 100℃ for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (414.6 mg). (Yield: 16.6%) 1H NMR (CDCl3, 400MHz) δ 9.97 (s, 1H), 8.40 (d, 1H), 7.33-7.27 (m, 2H), 6.46 (d, 1H), 5.02 (brs, 2H), 3.88 (s, 3H)

[1189] Preparation C4-2: 5-(4-aminopyrimidin-2-yl)thiophen-3-carbaldehyde

[1190] The titled compound was prepared in accordance with the same procedures as in Preparation C4-1, changing the boronic acid reagent to (4-formylthiophen-2-yl)boronic acid. 1H NMR (CD3OD, 400MHz) δ 9.86 (s, 1H), 8.45 (s, 1H), 8.19 (s, 1H), 8.08 (d, 1H), 6.41 (d, 1H)

[1191] Preparation C5-1: (4-(4-aminopyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)methanol

[1192] 4-(4-Aminopyrimidin-2-yl)-3-fluoro-5-methoxybenzaldehyde (the C4-1 intermediate, 100.0 mg, 0.40 mmol) was dissolved in anhydrous tetrahydrofuran (6.0 mL) and then sodium borohydride (15.3 mg, 0.40 mmol) was added dropwise thereto. Then, the mixed solution was stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture was diluted with dichloromethane and then water was slowly added thereto. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated to prepare the titled compound (69.0 mg), without further purification. (Yield: 68.4%) 1H NMR (CD3OD, 400MHz) δ 8.14 (d, 1H), 6.91 (s, 1H), 6.81 (d, 1H), 6.53 (d, 1H), 4.67 (s, 2H), 3.8 (s, 3H)

[1193] Preparation C5-2: (5-(4-aminopyrimidin-2-yl)thiophen-3-yl)methanol

[1194] The titled compound was prepared in accordance with the same procedures as in Preparation C5-1, using the C4-2 intermediate. 1H NMR (CD3OD, 400MHz) 8.04 (d, 1H), 7.82 (s, 1H), 7.38 (s, 1H), 6.36 (d, 1H), 4.60 (s, 2H)

[1195] Preparation C6-1: 2-(4-((dimethylamino)methyl)-2-fluoro-6-methoxyphenyl)pyrimidin-4-amine

[1196] 4-(4-Aminopyrimidin-2-yl)-3-fluoro-5-methoxybenzaldehyde (the C4-1 intermediate, 100 mg, 0.4 mmol) was dissolved in methanol (2.0 mL) and then 2.0M dimethylamine dissolved in tetrahydrofuran (0.4 mL, 0.8 mmol) and sodium acetate (33.2 mg, 0.40 mmol) were added dropwise thereto. Then, the mixed solution was stirred at room temperature overnight. Sodium borohydride (15.3 mg, 0.40 mmol) was added at room temperature to the reaction mixture, which was then stirred for 1 hour. After completion of the reaction, dichloromethane was added to the reaction mixture and then a saturated sodium hydrogen carbonate solution was added thereto. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated to prepare the titled compound (96.0 mg), without further purification. (Yield: 85.9%) 1H NMR (CD3OD, 400MHz) δ 8.14 (d, 1H), 6.92 (s, 1H), 6.81 (d, 1H), 6.53 (d, 1H), 3.8 (s, 3H), 3.54 (s, 2H), 2.30-2.28 (m, 6H)

[1197] Preparation C6-2: 1-((5-(4-aminopyrimidin-2-yl)thiophen-3-yl)methyl)azetidin-3-ol

[1198] The titled compound was prepared in accordance with the same procedures as in Preparation C6-1, using the C4-2 intermediate and changing the amine reagent to 3-hydroxyazetidine hydrochloride. The product was used in the subsequent reaction without further purification.

[1199] Preparation C7: 3-(6-amino-2-pyridyl)oxazolidin-2-one

[1200] 6-Bromopyridin-2-amine (300.0 mg, 1.734 mmol) was dissolved in anhydrous 1,4-dioxane (3.0 mL) and then oxazolidin-2-one (151.0 mg, 1.734 mmol), palladium(II) acetate (38.9 mg, 0.173 mmol), XantPhos (150.5 mg, 0.26 mmol), and cesium carbonate (1.41 g, 4.335 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 100℃ overnight. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (63.4 mg). (Yield: 20.4%) 1H NMR (CDCl3, 400MHz) δ 7.55 (d, 1H), 7.47 (t, 1H), 6.25 (d, 1H), 4.45 (t, 2H), 4.40-4.30 (s, 2H), 4.22 (t, 2H)

[1201] Preparation C8-1: 6-amino-2-(2-fluoro-6-methoxy-phenyl)pyridin-3-carbonitrile

[1202] 6-Amino-2-chloro-pyridin-3-carbonitrile (500.0 mg, 3.26 mmol) was dissolved in anhydrous 1,4-dioxane (5.0 mL) and water (1.0 mL) and then 2-fluoro-6-methoxyphenylboronic acid (608.7 mg, 3.58 mmol), tetrakis(triphenylphosphine)palladium(0) (376.2 mg, 0.33 mmol), and potassium carbonate (899.9mg, 6.51mmol) were added dropwise thereto. Then, the mixed solution was stirred at 100℃ for 17 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (355.8 mg, Yield: 44.9%). 1H NMR (CDCl3, 400MHz) δ 7.72 (d, 1H), 7.39 (q, 1H), 6.86-6.80 (m, 2H), 6.51 (d, 1H), 5.11 (s, 2H), 3.85 (s, 3H)

[1203] Preparation C8-2: 6-amino-2-(2,4-difluoro-6-methoxy-phenyl)pyridin-3-carbonitrile

[1204] The titled compound was prepared in accordance with the same procedures as in Preparation C8-1, changing the boronic acid reagent to (2,4-difluoro-6-methoxyphenyl)boronic acid. 1H NMR (CDCl3, 400MHz) 7.73 (d, 1H), 6.62-6.51 (m, 3H), 5.04 (s, 2H), 3.84 (s, 3H)

[1205] Example 1: (S)-cyclopropyl(4-(3-hydroxypiperidin-1-yl)-6-((2-(5-methylpyridin-3-yl)pyrimidin-4-yl)amino)pyridin-3-yl)methanone

[1206] (S)-(6-((2-Chloropyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)(cyclopropyl)methanone (Intermediate A1-1, 15.0 mg, 0.04 mmol) was dissolved in anhydrous 1,4-dioxane (0.4 mL) and then (5-methylpyridin-3-yl)boronic acid (10.9 mg, 0.08 mmol), bis(triphenylphosphine)palladium(II) dichloride (1.4 mg, 0.002 mmol), and 2.0M sodium carbonate solution (0.1 mL, 0.20 mmol) were added dropwise thereto. Then, the mixed solution was stirred in a microwave reactor for 1 hour. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (3.7 mg). (Yield: 21.4%) 1H NMR (CDCl3, 400MHz) δ 9.59 (s, 1H), 8.52-8.49 (m, 3H), 8.34-8.32 (m, 2H), 7.94 (s, 1H), 6.78 (d, 1H), 5.82-5.52 (brs, 1H), 4.13-4.05 (m, 2H), 3.31-3.28 (m, 1H), 3.14-3.11 (m, 2H), 2.54-2.51 (m, 1H), 2.46 (s, 3H), 2.18-2.15 (m, 1H), 1.80-1.79 (m, 1H), 1.65-1.63 (m, 2H), 1.28-1.25 (m, 2H), 1.09-1.07 (m, 1H), 1.06-1.01 (m, 1H) MS m / z= 431.1 (M+H)+

[1207] Example 2: (S)-(6-((2-(5-aminopyridin-3-yl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)(cyclopropyl)methanone

[1208] The titled compound (6.8 mg) was prepared in accordance with the same procedures as in Example 1, changing the boronic acid reagent to 3-aminopyridin-5-boronic acid pinacol ester. (Yield: 38.9%) 1H NMR (CDCl3, 400MHz) δ 9.17 (s, 1H), 8.50-8.49 (d, 1H), 8.36 (s, 1H), 8.3 (s, 1H), 8.13 (s, 1H), 8 (s, 1H), 7.89 (brs, 1H), 6.74 (d, 1H), 4.12-4.10 (m, 1H), 4.07 (brs, 2H), 3.32-3.27 (m, 1H), 3.12-3.06 (m, 2H), 2.54-2.52 (m, 1H), 2.15-2.12 (m, 1H), 1.81-1.79 (m, 1H), 1.54-1.51 (m, 2H), 1.28-1.26 (m, 2H), 1.26-1.25 (m, 1H), 1.07-1.06 (m, 1H) MS m / z= 432.0 (M+H)+

[1209] Example 3: (S)-cyclopropyl(4-(3-hydroxypiperidin-1-yl)-6-((2-(5-methoxypyridin-3-yl)pyrimidin-4-yl)amino)pyridin-3-yl)methanone

[1210] The titled compound (4.4 mg) was prepared in accordance with the same procedures as in Example 1, changing the boronic acid reagent to 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine. (Yield: 24.5%) 1H NMR (CDCl3, 400MHz) δ 9.38 (s, 1H), 8.52 (d, 1H), 8.37 (s, 1H), 8.36 (s, 1H), 8.32 (s, 1H), 8.29 (s, 1H), 8.23 (s, 1H), 8.22 (s, 1H), 6.8 (d, 1H), 5.41-5.31 (brs, 1H), 4.13-4.10 (m, 2H), 4.05 (s, 3H), 3.31-3.28 (m, 1H), 3.13-3.10 (m, 2H), 2.55-2.52 (m, 1H), 2.18-2.15 (m, 1H), 1.81-1.80 (m, 1H), 1.60-1.56 (m, 2H), 1.28-1.25 (m, 2H), 1.09-1.07 (m, 1H), 1.06-1.02 (m, 1H) MS m / z= 447.0 (M+H)+

[1211] Example 4: (S)-cyclopropyl(6-((2-(3-hydroxyphenyl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)methanone

[1212] The titled compound (1.4 mg) was prepared in accordance with the same procedures as in Example 1, changing the boronic acid reagent to 3-hydroxyphenylboronic acid. (Yield: 8.0%) 1H NMR (CD3OD, 400MHz) δ 8.46 (d, 1H), 8.24 (s, 1H), 7.99 (s, 1H), 7.85-7.81 (m, 2H), 7.35-7.28 (m, 2H), 6.96-6.93 (m, 1H), 3.90-3.88 (m, 1H), 3.57-3.54 (m, 1H), 3.46-3.43 (m, 1H), 3.02-2.91 (m, 1H), 2.89-2.83 (m, 2H), 2.03-1.96 (m, 1H), 1.82-1.62 (m, 1H), 1.50-1.45 (m, 1H), 1.29-1.20 (m, 2H), 1.19-1.12 (m, 2H) MS m / z= 432.1 (M+H)+

[1213] Example 5: (S)-cyclopropyl(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)methanone

[1214] The titled compound (1.4 mg) was prepared in accordance with the same procedures as in Example 1, changing the boronic acid reagent to 2-fluoro-6-methoxyphenylboronic acid. (Yield: 7.4%) 1H NMR (CDCl3, 400MHz) δ 8.62 (d, 1H), 8.40 (s, 1H), 7.82 (s, 1H), 7.54 (s, 1H), 7.39-7.30 (m, 2H), 6.84-6.80 (m, 2H), 3.88-3.86 (m, 1H), 3.82 (s, 3H), 3.34-3.30 (m, 1H), 3.13-3.07 (m, 1H), 3.04-3.02 (m, 1H), 3.01-2.99 (m, 2H), 2.62-2.58 (m, 1H), 2.24-2.21 (m, 1H), 1.90-1.84 (m, 2H), 1.31-1.26 (m, 2H), 1.04-1.02 (m, 2H) MS m / z= 464.1 (M+H)+

[1215] Example 6: cyclopropyl(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4-(3-hydroxyazetidin-1-yl)pyridin-3-yl)methanone

[1216] Step 1: (6-chloro-4-(3-hydroxyazetidin-1-yl)pyridin-3-yl)(cyclopropyl)methanone

[1217] Cyclopropyl(4,6-dichloropyridin-3-yl)methanone (1.0 g, 4.62 mmol) was dissolved in anhydrous dimethylformamide (23.1 mL) and then 3-hydroxyazetidine hydrochloride (0.61 g, 5.55 mmol) and diisopropylethylamine (1.26 mL, 9.25 mmol) were added dropwise thereto. The reaction mixture was stirred at room temperature overnight. Water was added to the reaction mixture and then the aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (0.94 g). (Yield: 80.5%) 1H NMR (CDCl3, 400MHz) δ 8.46 (s, 1H), 6.31 (s, 1H), 4.75-4.70 (m, 1H), 4.23-4.19 (m, 2H), 3.81-3.77 (m, 2H), 3.03-3.02 (m, 1H), 2.44-2.38 (m, 1H), 1.24-1.21 (m, 2H), 1.11-1.08 (m, 2H)

[1218] Step 2: cyclopropyl(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4-(3-hydroxyazetidin-1-yl)pyridin-3-yl)methanone

[1219] (6-Chloro-4-(3-hydroxyazetidin-1-yl)pyridin-3-yl)(cyclopropyl)methanone (63.4 mg, 0.25 mmol) was dissolved in anhydrous toluene (2.0 mL) and then 2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine (Intermediate C1-1, 50.0 mg, 0.23 mmol), tris(dibenzylideneacetone)dipalladium(0) (20.8 mg, 0.02 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (21.7 mg, 0.04 mmol), and cesium carbonate (111.4 mg, 0.34 mmol) were added dropwise thereto. Then, the mixed solution was refluxed under stirring at 110℃ overnight. After completion of the reaction, the reaction mixture was cooled to room temperature and then water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (10 mg). (Yield: 8.8%) 1H NMR (CD3OD, 400MHz) δ 8.52 (s, 1H), 8.45 (d, 1H), 7.45-7.41 (m, 2H), 7.25 (s, 1H), 6.97 (dd, 1H), 6.87 (dd, 1H), 4.57-4.54 (m, 1H), 4.08-4.04 (m, 2H), 3.81 (s, 3H), 3.66-3.62 (m, 2H), 2.58-2.55 (m, 1H), 1.13-1.05 (m, 4H) MS m / z= 436.0 (M+H)+

[1220] Example 7: (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol

[1221] (S)-1-(2-Chloro-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol (Intermediate A2-1, 40.0 mg, 0.12 mmol) was dissolved in anhydrous 1,4-dioxane (0.5 mL) and then 2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine (Intermediate C1-1, 20.9 mg, 0.09 mmol), tris(dibenzylideneacetone)dipalladium(0) (10.9 mg, 0.012 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (11.39 mg, 0.024 mmol), and cesium carbonate (77.8 mg, 0.24 mmol) were added dropwise thereto. Then, the mixed solution was stirred at 100℃ overnight. After completion of the reaction, the reaction mixture was cooled to room temperature and water was added thereto. The aqueous layer was extracted with ethyl acetate. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated and then purified by silica gel column chromatography to prepare the titled compound (10.6 mg). (Yield: 16.3%) 1H NMR (CDCl3, 400MHz) δ 8.4 (d, 1H), 8.09-8.08 (m, 2H), 7.83 (s, 1H), 7.60 (s, 1H), 7.51-7.50 (m, 1H), 7.44-7.42 (m, 1H), 6.96 (d, 1H), 6.84 (dd, 1H), 4.49-4.46 (m, 1H), 4.10-4.07 (m, 2H), 3.81 (s, 3H), 3.70-3.61 (m, 1H), 3.59-3.56 (m, 2H), 3.31-3.30 (m, 1H), 3.29-3.27 (m, 1H), 2.72-2.60 (m, 1H), 2.45-2.40 (m, 1H), 2.14-2.08 (m, 4H), 1.98-1.97 (m, 1H), 1.33-1.31 (m, 1H), 1.30-1.29 (m, 1H) MS m / z= 546.2 (M+H)+

[1222] Example 8: (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol

[1223] The titled compound (2.6 mg) was prepared in accordance with the same procedures as in Example 7, using Intermediates A6-1 and C1-1. (Yield: 7.9%) 1H NMR (CDCl3, 400MHz) δ 8.60 (d, 1H), 8.23 (s, 1H), 8.06 (s, 1H), 7.90 (s, 1H), 7.78 (s, 1H), 7.45 (s, 1H), 7.37-7.31 (m, 2H), 6.83-6.80 (m, 2H), 3.96-3.95 (m, 1H), 3.82 (s, 3H), 3.45-3.44 (m, 2H), 3.30-3.24 (m, 2H), 1.92-1.83 (m, 4H) MS m / z= 554.1 (M+H)+

[1224] Example 9: (R)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol

[1225] The titled compound (2.8 mg) was prepared in accordance with the same procedures as in Example 7, using Intermediates B5-2 and C1-1. (Yield: 7.9%) 1H NMR (CDCl3, 400MHz) δ 8.60 (d, 1H), 8.22 (s, 1H), 8.06 (s, 1H), 7.97 (s, 1H), 7.90 (s, 1H), 7.49 (s, 1H), 7.37-7.31 (m, 1H), 7.29-7.27 (m, 1H), 6.83-6.80 (m, 2H), 3.95-9.94 (m, 1H), 3.84 (s, 3H), 3.45-3.42 (m, 2H), 3.33-3.28 (m, 1H), 3.24-3.21 (m, 1H), 1.92-1.83 (m, 4H) MS m / z= 554.1 (M+H)+

[1226] Example 10: 1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)azetidin-3-ol

[1227] The titled compound (7.5 mg) was prepared in accordance with the same procedures as in Example 7, using Intermediate B5-1 and C1-1. (Yield: 15.4%) 1H NMR (CD3OD, 400MHz) δ 8.39 (d, 1H), 7.89 (s, 1H), 7.44-7.40 (m, 1H), 7.37 (d, 1H), 6.99 (s, 1H), 6.96 (d, 1H), 6.85 (dd, 1H), 4.59-4.57 (m, 1H), 4.41-4.39 (m, 2H), 3.93-3.88 (m, 4H), 3.81 (s, 3H), 3.56-3.50 (m, 2H), 2.97-2.87 (m, 1H), 1.92-1.87 (m, 2H), 1.74-1.68 (m, 2H) MS m / z= 476.1 (M+H)+

[1228] Example 11: (S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol

[1229] The titled compound (6.0 mg) was prepar...

Claims

1.A compound of Formula 1a or pharmaceutically acceptable salt thereof:<Formula 1a>wherein,R1and R2form a heterocycloalkyl together with the nitrogen atom to which they are bonded, wherein the heterocycloalkyl is optionally substituted with one or two groups selected from the group consisting of halogen, amino, hydroxy, C1∼C6alkyl, C1∼C6alkoxy, C1∼C6alkyl substituted with halogen, C1∼C6alkyl substituted with hydroxy, C3∼C6cycloalkyl, C3∼C6cycloalkyl substituted with hydroxy, mono- or di-C1∼C6alkylamino, aminocarbonyl, C1∼C6alkylcarbonylamino, and mono- or di-C1∼C6alkylamino-C1∼C6alkyl,X is -C(R3)= or -N=,R3is hydrogen, halogen, cyano, nitro, amino, C1∼C3alkyl, C1∼C3alkyl substituted with halogen, hydroxycarbonyl, C1∼C3alkoxycarbonyl, aminocarbonyl, mono- or di-C1∼C3alkylaminocarbonyl, or C1∼C3alkylsulfonyl,R4is, independently each other, halogen, amino, hydroxy, C1∼C6alkyl, C1∼C6alkyl substituted with hydroxy, C1∼C6alkoxy, C3∼C6cycloalkyl, aldehyde, mono- or di-C1∼C3alkylamino, mono- or di-C1∼C3alkylamino-C1∼C6alkyl, C1∼C6alkoxycarbonyl, mono- or di-C1∼C6alkylaminocarbonyl, C1∼C6alkylaminocarbonyl substituted with halogen, C3∼C6cycloalkylaminocarbonyl, C3∼C6cycloalkylaminocarbonyl substituted with halogen, C3∼C6cycloalkylaminocarbonyl substituted with hydroxy, heterocycloalkyl-C1∼C3alkyl optionally substituted with hydroxy, or heterocycloalkylcarbonyl optionally substituted with halogen,o is 0, 1, 2, or 3,L is a bond, -C(O)-, -(CH2)n-, -C(O)NH-, or -C≡C-,n is 1, 2, or 3,Q is a bond; C3∼C6cycloalkyl; a 3- to 12-membered heterocycloalkyl having one to three heteroatoms selected from N, O and S; a 5- to 12-membered heteroaryl having one to three heteroatoms selected from N, O and S; or a 5- to 12-membered aryl,m is 1, 2, or 3,Y is, independently each other, hydrogen, hydroxy, halogen, amino, C1∼C6alkyl, C1∼C6alkyl substituted with hydroxy, C1∼C6alkyl substituted with halogen, C1∼C6alkyl substituted with mono- or di-C1∼C3alkylamino, C1∼C6alkoxy, C1∼C6alkoxy substituted with C1∼C3alkoxy, C1∼C6alkoxy substituted with halogen, C1∼C6alkoxy substituted with mono- or di-C1∼C3alkylamino, C1∼C6alkoxy-C1∼C6alkyl, C3∼C6cycloalkyl, C3∼C6cycloalkyl-C1∼C3alkyl, C3∼C6cycloalkyl-C1∼C3alkyl substituted with halogen, C1∼C3alkylcarbonyl, C3∼C6cycloalkyl-aminocarbonyl substituted with hydroxy, mono- or di-C1∼C3alkylamino, C1∼C6alkylamino substituted with mono- or di-C1∼C3alkylamino, aminocarbonyl-C1∼C6alkyl, C1∼C3alkoxycarbonyl-C1∼C6alkyl, C1∼C3alkylcarbonylamino, mono- or di-C1∼C6alkylaminocarbonyl, mono- or di-C1∼C6alkylaminocarbonylamino, or mono- or di-C1∼C6alkylaminocarbonyl-C1∼C6alkyl, ora heterocycloalkyl-containing group selected from the group consisting of azetidinyl; azetidinyl-C1∼C6alkyl; tetrahydropyranyl; tetrahydrofuranyl; pyrrolidinyl; pyrrolidinyl-C1∼C3alkyl; piperidinyl; piperidinyl-C1∼C3alkyl; piperidinylcarbonyl; piperidinyloxy; piperazinyl; piperazinyl-C1∼C3alkyl; piperazinylcarbonyl; oxetanyl; morpholinyl; morpholinyl-C1∼C3alkyl; and morpholinylcarbonyl, wherein the heterocycloalkyl of the heterocycloalkyl-containing group is optionally substituted with one to four groups selected from the group consisting of halogen, hydroxy, amino, oxo, C1∼C3alkyl, C1∼C3alkyl substituted with hydroxy, and mono- or di-C1∼C3alkylamino.2.The compound or pharmaceutically acceptable salt thereof as claimed in claim 1, wherein R1and R2form piperidine, azetidine, pyrrolidine, piperazine, or 2,8-diazaspiro[4.5]decane together with the nitrogen atom to which they are bonded.3.The compound or pharmaceutically acceptable salt thereof as claimed in claim 1, wherein X is -N=.4.The compound or pharmaceutically acceptable salt thereof as claimed in claim 1, wherein X is -C(R3)= and R3is H, -F, -Cl, -CH3, -CN, -NO2, -NH2, -C(O)OH, -C(O)OCH3, -C(O)NH2, -C(O)N(CH3)2, or -SO2CH3.5.The compound or pharmaceutically acceptable salt thereof as claimed in claim 1, wherein R4is, independently each other, halogen, amino, hydroxy, C1∼C6alkyl, C1∼C6alkyl substituted with hydroxy, C1∼C6alkoxy, aldehyde, mono- or di-C1∼C3alkylamino-C1∼C6alkyl, C1∼C6alkoxycarbonyl, mono- or di-C1∼C6alkylaminocarbonyl, azetidinyl-C1∼C3alkyl substituted with hydroxy, azetidinylcarbonyl optionally substituted with one or two halogens, or pyrrolidinylcarbonyl optionally substituted with one or two halogens.6.The compound or pharmaceutically acceptable salt thereof as claimed in claim 1, wherein Q is a bond, C3∼C6cycloalkyl, tetrahydropyranyl, pyrrolidinyl, phenyl, pyridinyl, pyrazolyl, thiazolyl, imidazo[1,2-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridin-6-yl,2H-benzo[b][1,4]oxazin-3(4H)-onyl, 3,4-dihydroquinolin-2(1H)-onyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, 2H-pyrido[3,2-b]-1,4-oxazin-3(4H)-onyl, 1,4-dihydro-2H-benzo[d][1,3]oxazin-2-onyl, or 3,4-dihydro-1,8-naphthyridin-2(1H)-onyl.7.The compound or pharmaceutically acceptable salt thereof as claimed in claim 1, wherein Y is, independently each other, hydrogen, hydroxy, halogen, amino, C1∼C6alkyl, C1∼C6alkyl substituted with hydroxy, C1∼C6alkyl substituted with halogen, C1∼C6alkyl substituted with mono- or di-C1∼C3alkylamino, C1∼C6alkoxy, C1∼C6alkoxy substituted with C1∼C3alkoxy, C1∼C6alkoxy substituted with halogen, C1∼C6alkoxy substituted with mono- or di-C1∼C3alkylamino, C1∼C6alkoxy-C1∼C6alkyl, C3∼C6cycloalkyl, C3∼C6cycloalkyl-C1∼C3alkyl, C3∼C6cycloalkyl-C1∼C3alkyl substituted with halogen, C1∼C3alkylcarbonyl, C3∼C6cycloalkyl-aminocarbonyl substituted with hydroxy, mono- or di-C1∼C3alkylamino, C1∼C6alkylamino substituted with mono- or di-C1∼C3alkylamino, aminocarbonyl-C1∼C6alkyl, C1∼C3alkoxycarbonyl-C1∼C6alkyl, C1∼C3alkylcarbonylamino, mono- or di-C1∼C6alkylaminocarbonyl, mono- or di-C1∼C6alkylaminocarbonylamino, or mono- or di-C1∼C6alkylaminocarbonyl-C1∼C6alkyl.8.The compound or pharmaceutically acceptable salt thereof as claimed in claim 1, wherein one of Y is a heterocycloalkyl-containing group selected from the group consisting of azetidinyl; azetidinylmethyl; tetrahydropyranyl; tetrahydrofuranyl; pyrrolidinyl; pyrrolidinylmethyl; pyrrolidinylethyl; piperidinyl; piperidinylmethyl; piperidinylcarbonyl; piperidinyloxy; piperazinyl; piperazinylmethyl; piperazinylcarbonyl; oxetanyl; morpholinyl; morpholinylmethyl; morpholinylethyl; and morpholinylcarbonyl, and the remaining Y is hydrogen.9.The compound or pharmaceutically acceptable salt thereof as claimed in claim 8, wherein the heterocycloalkyl of the heterocycloalkyl-containing group is substituted with one to four groups selected from the group consisting of halogen, hydroxy, amino, oxo, C1∼C3alkyl, C1∼C3alkyl substituted with hydroxy, and mono- or di-C1∼C3alkylamino.10.A compound or pharmaceutically acceptable salt thereof, which is selected from the group consisting of:(S)-cyclopropyl(4-(3-hydroxypiperidin-1-yl)-6-((2-(5-methylpyridin-3-yl)pyrimidin-4-yl)amino)pyridin-3-yl)methanone;(S)-(6-((2-(5-aminopyridin-3-yl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)(cyclopropyl)methanone;(S)-cyclopropyl(4-(3-hydroxypiperidin-1-yl)-6-((2-(5-methoxypyridin-3-yl)pyrimidin-4-yl)amino)pyridin-3-yl)methanone;(S)-cyclopropyl(6-((2-(3-hydroxyphenyl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)methanone;(S)-cyclopropyl(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4-(3-hydroxypiperidin-1-yl)pyridin-3-yl)methanone;cyclopropyl(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4-(3-hydroxyazetidin-1-yl)pyridin-3-yl)methanone;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;(R)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)azetidin-3-ol;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(5-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(4-(tetrahydro-2H-pyran-4-yl)phenyl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(4-(4-methylpiperazin-1-yl)phenyl)pyridin-4-yl)piperidin-3-ol;(S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-morpholino-[3,3'-bipyridin]-4-yl)piperidin-3-ol;(S)-1-(2-((2-(4-(hydroxymethyl)thiophen-2-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2,6-difluorophenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(3,6-difluoro-2-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2,3-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2-ethoxy-6-fluorophenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-([1,2,4]triazolo[1,5-a]pyridin-7-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(pyrazolo[1,5-a]pyridin-3-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(quinoxalin-6-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(8-fluoroquinolin-7-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-((4-methylpiperazin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;(S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;(S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-(morpholinomethyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;(S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-((4-hydroxypiperidin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-carboxamide;(S)-1-(2-((6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-(6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(4-methylpiperazin-1-yl)methanone;(S)-(6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(morpholino)methanone;(S)-(6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4'-(3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(4-hydroxypiperidin-1-yl)methanone;(S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-(((S)-3-fluoropyrrolidin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;(3S)-1-(2-((5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;(3S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-((3-hydroxypyrrolidin-1-yl)methyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;N-(4-(3-(dimethylamino)pyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-3-methylpyrrolidin-3-yl)methanol;N-(4-(4-((dimethylamino)methyl)-4-fluoropiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(4-(2,2-difluoroethyl)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)methanol;(3S)-1-(6'-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;1-((6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4'-((S)-3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)methyl)piperidin-3-ol;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-carboxamide;(R)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-carboxamide;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(R)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(6'-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4'-((S)-3-hydroxypiperidin-1-yl)-[3,3'-bipyridin]-6-yl)(4-hydroxypiperidin-1-yl)methanone;(S)-1-(6'-((4-aminopiperidin-1-yl)methyl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;(S)-1-(6'-ethoxy-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;(S)-1-(6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-6'-(trifluoromethyl)-[3,3'-bipyridin]-4-yl)piperidin-3-ol;(3S)-1-(2-((6-(2-fluoro-6-methoxyphenyl)-5-methylpyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinonitrile;methyl 2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinate;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(imidazo[1,2-a]pyridin-6-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(5-([1,2,4]triazolo[4,3-a]pyridin-6-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)nicotinonitrile;N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;1-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)cyclopropan-1-ol;1-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)ethan-1-ol;2-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-yl)-2-methylpropan-1-ol;2-(2-fluoro-6-methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;(S)-1-(2-((2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine;methyl 6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinate;(S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(3S)-1-(2-((5-chloro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)pyridin-2-amine;(R)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-3-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)pyridin-2-ol;(S)-1-(6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-methylpiperidin-4-yl)oxy)-[2,3'-bipyridin]-4'-yl)piperidin-3-ol;(S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-6-amine;(S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(1-methylpiperidin-4-yl)-[3,3'-bipyridin]-6-amine;2-(2-fluoro-6-methoxyphenyl)-N-(5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-4-(3-(2,2,2-trifluoroethyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;2-(2-fluoro-6-methoxyphenyl)-N-(4-(3-(fluoromethyl)piperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;N-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-yl)acetamide;2-(2-fluoro-6-methoxyphenyl)-N-(5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-4-(4-(trifluoromethyl)piperidin-1-yl)pyridin-2-yl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-(2,8-diazaspiro[4.5]decan-8-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-(2,8-diazaspiro[4.5]decan-2-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(3R,4R)-4-fluoro-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3R,4R)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)-4-(hydroxymethyl)piperidin-3-ol;(R)-N-(4-(3-aminopyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(2-(1-methylpiperidin-4-yl)thiazol-5-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-4-(3-aminopiperidin-1-yl)-N-(2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-yl)-6'-(tetrahydro-2H-pyran-4-yl)-[3,3'-bipyridin]-6-amine;4-((S)-3-aminopiperidin-1-yl)-N-(5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-amine;(S)-(4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)methanol;(S)-(4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)methanol;(S)-(4-(4-((4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)methanol;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(4-((dimethylamino)methyl)-2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(4-((dimethylamino)methyl)-2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(4-((dimethylamino)methyl)-2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinamide;2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-N,N-dimethylnicotinamide;4-((S)-3-aminopiperidin-1-yl)-N-(5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(7-fluoroquinoxalin-6-yl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(3-methoxypropyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;2-(2-fluoro-6-methoxyphenyl)-N-(4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;(S)-4-(3-aminopiperidin-1-yl)-N6-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-N6',N6'-dimethyl-[3,3'-bipyridin]-6,6'-diamine;(S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(pyrrolidin-1-yl)-[3,3'-bipyridin]-6-amine;(S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(piperidin-1-yl)-[3,3'-bipyridin]-6-amine;(S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-morpholino-[3,3'-bipyridin]-6-amine;(S)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-(methylamino)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(R)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-(methylamino)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-2-(2-fluoro-6-methoxyphenyl)-N-(4-(3-(methylamino)pyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;(S)-N-(4-(3-(ethylamino)pyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(R)-N-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)pyrrolidin-3-yl)acetamide;(S)-3-(6-((4-(3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyridin-2-yl)oxazolidin-2-one;(S)-N-(1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)pyrrolidin-3-yl)acetamide;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinamide;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)-N,N-dimethylnicotinamide;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-2-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide;(S)-2-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)ethan-1-ol;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;2-(2-fluoro-6-methoxyphenyl)-N-(4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)pyrimidin-4-amine;N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-4-(2-methyl-2,8-diazaspiro[4.5]decan-8-yl)-6'-morpholino-[3,3'-bipyridin]-6-amine;(S)-3-(6-((4-(3-aminopiperidin-1-yl)-6'-morpholino-[3,3'-bipyridin]-6-yl)amino)pyridin-2-yl)oxazolidin-2-one;2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)amino)nicotinic acid;2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)amino)nicotinamide;6-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)-N,N-dimethylnicotinamide;6-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinamide;2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinamide;2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinamide;(3S)-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)pyridin-4-yl)piperidin-3-ol;4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)pyridin-2-amine;N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;4-(4-(2-(dimethylamino)ethyl)piperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-morpholino-[3,3'-bipyridin]-6-amine;(3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;N²-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)pyridin-2-amine;4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-amine;4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-amine;4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-amine;4-((S)-3-aminopiperidin-1-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;6-((5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinamide;(S)-1-(2-((2-(2-fluoro-4-(hydroxymethyl)-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-3-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)propanamide;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(azetidin-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N²-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;N²-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;(S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;N2-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;(S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-5-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridazin-3-amine;(S)-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)(4-methylpiperazin-1-yl)methanone;(3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(trifluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;N²-(4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2-fluoro-6-methoxyphenyl)pyridin-2,5-diamine;(S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((5-amino-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;methyl (S)-4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxybenzoate;(S)-4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxy-N-methylbenzamide;(S)-4-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxy-N,N-dimethylbenzamide;(S)-1-(2-((2-(4-((3-hydroxyazetidin-1-yl)methyl)thiophen-2-yl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-3-fluoro-4-(4-((4-(3-hydroxypiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-5-methoxybenzaldehyde;(S)-1-(2-((2-(2-fluoro-6-methoxy-4-((methylamino)methyl)phenyl)pyrimidin-4-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)-N-((R)-1-methylpyrrolidin-3-yl)nicotinamide;6-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-N-((1R,3R)-3-hydroxycyclopentyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-N-((1R,3S)-3-hydroxycyclopentyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-N-(3-hydroxycyclobutyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-N-((1R,2R)-2-hydroxycyclobutyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;N-(3,3-difluorocyclobutyl)-6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;N-((1R,3R)-3-aminocyclopentyl)-6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;N-((1R,3S)-3-aminocyclopentyl)-6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;6-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-N-((1R,3R)-3-hydroxycyclopentyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;6-((5-amino-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)amino)-N-((1R,3S)-3-hydroxycyclopentyl)-4-((S)-3-hydroxypiperidin-1-yl)nicotinamide;6-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-4-((S)-3-hydroxypiperidin-1-yl)-N-((R)-1-methylpyrrolidin-3-yl)nicotinamide;N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3S,5S)-3-amino-5-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(3R,4R)-3-amino-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-4-ol;N-(4-((3S,5S)-3-amino-5-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;(3R,4R)-3-amino-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-4-ol;(1S,4S)-4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)(methyl)amino)cyclohexan-1-ol;N2-(4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2,5-diamine;N2-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2,5-diamine;(S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(trifluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;(S)-1-(2-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(5-((1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)ethynyl)-2-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)pyridin-4-yl)piperidin-3-ol;(3S)-1-(5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)-2-((6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((6-(2,4-difluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)amino)-5-((tetrahydro-2H-pyran-4-yl)ethynyl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((5-amino-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((5-amino-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(3S)-1-(2-((5-amino-6-(2,4-difluoro-6-methoxyphenyl)pyridin-2-yl)amino)-5-(2-(tetrahydro-2H-pyran-4-yl)ethyl)pyridin-4-yl)piperidin-3-ol;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-methoxy-2-methylpropyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(2-methoxyethoxy)-[3,3'-bipyridin]-6-amine;(S)-(3,3-difluoroazetidin-1-yl)(4-(4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)methanone;(4-(4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)((S)-3-fluoropyrrolidin-1-yl)methanone;(4-(4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((S)-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)((R)-3-fluoropyrrolidin-1-yl)methanone;(S)-(4-(4-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)(3,3-difluoropyrrolidin-1-yl)methanone;(S)-1-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)-2-methylpropan-2-ol;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(azetidin-3-ylmethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-((R)-pyrrolidin-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-((S)-pyrrolidin-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-4-(3-aminopiperidin-1-yl)-N6'-(2-(dimethylamino)ethyl)-N6-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-[3,3'-bipyridin]-6,6'-diamine;(S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(piperazin-1-yl)-[3,3'-bipyridin]-6-amine;(S)-(2-(4-((4-(3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluorophenyl)methanol;(S)-(2-(4-((4-(3-aminopiperidin-1-yl)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluorophenyl)methanol;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(1-methoxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-((3,3-difluorocyclobutyl)methyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(fluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-4-(3-aminopiperidin-1-yl)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-6'-(piperidin-4-yl)-[3,3'-bipyridin]-6-amine;(S)-4-(3-aminopiperidin-1-yl)-6'-(2-(dimethylamino)ethoxy)-N-(2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)-[3,3'-bipyridin]-6-amine;(S)-1-(4'-(3-aminopiperidin-1-yl)-6'-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-[3,3'-bipyridin]-6-yl)-3-ethylurea;(4-(4-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)pyrimidin-2-yl)-3-fluoro-5-methoxyphenyl)((R)-3-fluoropyrrolidin-1-yl)methanone;N-(4-((2R,5S)-5-amino-2-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3R,4S)-3-amino-4-methoxypiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3R,4R)-3-amino-4-methoxypiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)(morpholino)methanone;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-6-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one;(S)-1-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)pyrrolidin-2-one;(S)-7-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one;(S)-7-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-4-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one;(S)-6-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-8-methyl-3,4-dihydroquinolin-2(1H)-one;(S)-6-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1-methyl-3,4-dihydroquinolin-2(1H)-one;(S)-1-(2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)-5-(1-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-4-yl)piperidin-3-ol;(S)-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)(piperazin-1-yl)methanone;(S)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-((methylamino)methyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(R)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-((methylamino)methyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3R,4R)-4-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;6-(4-((S)-3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one;(S)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-methylpiperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-(fluoromethyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(R)-N-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-(3-(difluoromethyl)piperidin-1-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-7-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-4-methyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one;(S)-7-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one;(S)-6-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;methyl (S)-2-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-1H-pyrazol-1-yl)-2-methylpropanoate;(S)-N-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)acetamide;(S)-3-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-N,N-dimethylbenzamide;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(3-methyl-4-(trifluoromethoxy)phenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-fluoro-3-methylphenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-isopropoxy-3,5-dimethylphenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-methoxy-3,5-dimethylphenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-morpholinophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(3-methyl-4-morpholinophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-(4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)(4-(2-hydroxyethyl)piperazin-1-yl)methanone;4-(4-((S)-3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-N-((1r,4S)-4-hydroxycyclohexyl)benzamide;(S)-4-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2-fluoro-N,N-dimethylbenzamide;(S)-1-(3-(4-(3-aminopiperidin-1-yl)-6-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)phenyl)ethan-1-one;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(3-chloro-4-fluorophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(4-fluoro-3-(trifluoromethyl)phenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(3,4-difluorophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(3R,4R)-4-amino-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;(S)-N-(4-(3-aminopiperidin-1-yl)-5-(3-(dimethylamino)-4-fluorophenyl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3R,4S)-4-amino-3-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-((S)-tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((S)-3-aminopiperidin-1-yl)-5-(1-((R)-tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;N-(4-((3S,4S)-4-amino-3-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3S,5R)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3S,5R)-3-amino-5-(trifluoromethyl)piperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;(3S,5S)-5-amino-1-(5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-((2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-4-yl)piperidin-3-ol;N-(4-((3R,4S)-4-amino-3-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3S,4R)-4-amino-3-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;(S)-N-(4-(3-aminopiperidin-1-yl)-5-((4-methyltetrahydro-2H-pyran-4-yl)ethynyl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;(S)-4-((4-(3-aminopiperidin-1-yl)-6-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)ethynyl)tetrahydro-2H-pyran-4-ol;(S)-4-(4-(3-aminopiperidin-1-yl)-6-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)-2-methylbut-3-yn-2-ol;(S)-4-(4-(3-aminopiperidin-1-yl)-6-((2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-yl)amino)pyridin-3-yl)but-3-yn-1-ol;4-((S)-3-aminopiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-(methylsulfonyl)pyridin-2-yl)pyridin-2-amine;2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinonitrile;2-(2,4-difluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinonitrile;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;6-((4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;6-((4-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;6-((4-((S)-3-aminopiperidin-1-yl)-6'-morpholino-[3,3'-bipyridin]-6-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;N-(4-((3S,5R)-3-amino-5-fluoropiperidin-1-yl)-5-(2-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;2-(2-fluoro-6-methoxyphenyl)-6-((4-((S)-3-hydroxypiperidin-1-yl)-5-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)nicotinonitrile;6-((4-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-ethyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-cyclopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;6-((4-((S)-3-aminopiperidin-1-yl)-5-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;6-((5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-4-((3R,4R)-4-fluoro-3-hydroxypiperidin-1-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)nicotinonitrile;N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(6-(2-fluoro-6-methoxyphenyl)-5-nitropyridin-2-yl)pyridin-2-amine;N-(4-((3S,5R)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;N-(4-((3S,5S)-3-amino-5-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;6-((4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2-fluoro-6-methoxyphenyl)-nicotinonitrile;6-((4-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile;N-(4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(2,4-difluoro-6-methoxyphenyl)pyrimidin-4-amine;6-((4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-isopropyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-2-(2,4-difluoro-6-methoxyphenyl)nicotinonitrile; and4-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(1-(difluoromethyl)-1H-pyrazol-4-yl)-N-(5-fluoro-6-(2-fluoro-6-methoxyphenyl)pyridin-2-yl)pyridin-2-amine.11.A pharmaceutical composition for inhibiting hematopoietic progenitor kinase 1 comprising the compound or pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 10 as an active ingredient.12.The pharmaceutical composition as claimed in claim 11, for preventing or treating a blood cancer or a solid tumor.13.The pharmaceutical composition as claimed in claim 11, for preventing or treating melanoma, blastoma, sarcoma, lymphoma, leukemia, bladder cancer, brain tumor, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, endometrioma, hepatic cancer, laryngeal cancer, lung cancer, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, thyroid cancer, ependymoma, glioblastoma, bullous cell tumor, neuroblastoma, osteosarcoma, rhabdomyosarcoma, or nephroblastoma.14.A method for inhibiting hematopoietic progenitor kinase 1 in a mammal, which comprises administering a therapeutically effective amount of the compound or pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 10 to the mammal in need thereof.

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