Bicyclic fused-ring derivative or salt thereof and pharmaceutical composition including the same

Abstract

The present disclosure relates to a bicyclic fused-ring (for example, pteridine, pyridopyrimidine, pyridopyrazine, quinazoline, naphthyridine, or quinoxaline) derivative or a pharmaceutically acceptable salt thereof inducing activation of a triggering receptor expressed on myeloid cells 2 (TREM2), a pharmaceutical composition including the same, and a use thereof. The bicyclic fused-ring derivative or a pharmaceutically acceptable salt thereof may be useful in treatment and prevention of TREM2-mediated neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), FTLD-like syndrome, Parkinson's disease, Huntington's disease and Nasu-Hakola disease.

Description

BICYCLIC FUSED-RING DERIVATIVE OR SALT THEREOF AND PHARMACEUTICAL COMPOSITION INCLUDING THE SAME

[0001] Cross-reference to Related Applications

[0002] This application claims priority to and the benefits of Korean Patent Application No. 10-2024-0098366 filed with the Korean Intellectual Property Office on July, 25, 2024, the disclosure of which is incorporated herein by reference in its entirety.

[0003] The present disclosure relates to a bicyclic fused-ring (for example, pteridine, pyridopyrimidine, pyridopyrazine, quinazoline, naphthyridine, or quinoxaline) derivative or a pharmaceutically acceptable salt thereof inducing activation of a triggering receptor expressed on myeloid cells 2 (TREM2), a pharmaceutical composition including the same, and a use thereof.

[0004] A triggering receptor expressed on myeloid cells 2 (hereinafter, TREM2) is a transmembrane receptor of immunoglobulin superfamily. TREM2 is mainly expressed on immune cells such as macrophages, osteoclasts and microglia. In microglia that are responsible for immune function of a central nervous system, TREM2 plays an important role in inducing activation of the microglia to fight against and remove foreign substances that invade the brain [DeczkowskaA. et al. 2020]. TREM2 expressed in the human body includes an extracellular domain, a single transmembrane helix and a short cytosolic tail, and consists of 230 amino acids. Ligands that bind to TREM2 include endotoxin, bacteria, phospholipids, phosphatidylserine, lipoproteins, amyloid beta oligomers (oligomeric Aβ) and the like [Hammond, T. R. et al. 2019]. It is well known that a signal transducing process by TREM2 activation is performed through an interaction with DAP12 (DNAX activating protein of 12 Kda), an adaptor protein, when ligand mediates downstream signal transduction after binding [Kobayashi M. et al. 2016].

[0005] The TREM2 gene is associated with diseases such as Nasu-Hakola disease (NHD), Alzheimer's disease (AD) and frontotemporal dementia (FTD), and mutants of TREM2 may increase the incidence of Alzheimer's disease up to three times the normal level.

[0006] When a mouse having the TREM2 gene deleted or mutated was crossed with a 5XFAD mouse, an animal model for Alzheimer's disease, the phenotype of Alzheimer's disease was significantly observed compared to a mouse having the TREM2 gene not deleted [Urich et. al 2017]. It was identified that loss of TREM2 function in a central nervous system of other rodents affected activation of microglia, causing a pathological phenomenon of Alzheimer's disease [Parhizkar et al. 2019].

[0007] In a rodent model with increased TREM2 expression, the brain of a 5XFAD mouse had volume decrease and morphological change in the amyloid plaque [Lee et al. 2018]. Changes in immunohistochemical markers associated with brain amyloid pathology were also observed.

[0008] Neurodegenerative diseases that may be treated by signal transduction through TREM2 activation include Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), FTLD-like syndrome, Parkinson's disease, Huntington's disease, Nasu-Hakola disease (NHD, also referred to as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy), multiple sclerosis (MS), Guillain-Barr syndrome, chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis (ALS), rheumatoid arthritis, prion disease and stroke, but are not limited thereto. Accordingly, medical needs for the development of TREM2 activity regulators are increasing to address these indications.

[0009] The inventors of the present disclosure have found that a bicyclic fused-ring (for example, pteridine, pyridopyrimidine, pyridopyrazine, quinazoline, naphthyridine, or quinoxaline) derivative or a pharmaceutically acceptable salt thereof induces activation of TREM2. Accordingly, the bicyclic fused-ring derivative or a pharmaceutically acceptable salt thereof may be useful in treatment and prevention of TREM2-mediated neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), FTLD-like syndrome, Parkinson's disease, Huntington's disease and Nasu-Hakola disease.

[0010] Accordingly, the present disclosure is directed to providing the bicyclic fused-ring derivative or a pharmaceutically acceptable salt thereof, a pharmaceutical composition including the same and a use thereof.

[0011] According to one aspect of the present disclosure, there is provided a bicyclic fused-ring (for example, pteridine, pyridopyrimidine, pyridopyrazine, quinazoline, naphthyridine, or quinoxaline) derivative or a pharmaceutically acceptable salt thereof.

[0012] According to another aspect of the present disclosure, there is provided a pharmaceutical composition including the bicyclic fused-ring derivative or a pharmaceutically acceptable salt thereof as an active ingredient.

[0013] According to still another aspect of the present disclosure, there is provided a use of the bicyclic fused-ring derivative or a pharmaceutically acceptable salt thereof in manufacturing drugs for activation of TREM2.

[0014] It has been found by the present disclosure that a bicyclic fused-ring (for example, pteridine, pyridopyrimidine, pyridopyrazine, quinazoline, naphthyridine, or quinoxaline) derivative or a pharmaceutically acceptable salt thereof induces activation of TREM2. Accordingly, the compound according to the present disclosure or a pharmaceutically acceptable salt thereof can be useful in treating and preventing various neurodegenerative diseases that may be treated by signal transduction through TREM2 activation, such as Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), FTLD-like syndrome, Parkinson's disease, Huntington's disease, Nasu-Hakola disease (also referred to as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy), multiple sclerosis (MS), Guillain-Barr syndrome, chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis (ALS), rheumatoid arthritis, prion disease, or stroke.

[0015] According to one embodiment of the present disclosure, there may be provided a compound selected from the group consisting of a compound represented by the following Chemical Formula 1, optical isomers thereof, solvates thereof, hydrates thereof, and pharmaceutically acceptable salts thereof:

[0016] [Chemical Formula 1]

[0017]

[0018] in Chemical Formula 1,

[0019] X1, X2, X3and X4are each independently N or CH, provided that at least two of X1to X4are N;

[0020] R1and R2are each independently hydrogen, halogen, C1-6alkyl or C1-6haloalkyl;

[0021] A is C6-12aryl or 5- to 12-membered heteroaryl;

[0022] B is C6-12aryl, 5- to 12-membered heteroaryl or 3- to 12-membered heterocycloalkyl;

[0023] C is C6-12aryl or 5- to 12-membered heteroaryl;

[0024] R3are each independently selected from the group consisting of halogen, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6aminoalkyl and C1-6haloalkoxy;

[0025] R4are each independently selected from the group consisting of halogen, -CN, -NO2and -(C(Rx)2)e-Ry;

[0026] Rxare each independently hydrogen, halogen, C1-3alkyl or C1-3haloalkyl;

[0027] e is an integer of 0 to 3;

[0028] Ryis -Ra, -ORa, -SRa, -N(Ra)2, -CORa, -SO2Ra, -CO2Ra, -OCORa, -CON(Ra)2, -SO2N(Ra)2, -NHCORaor -NHSO2Ra;

[0029] Raare each independently hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6aminoalkyl, C3-10cycloalkyl or 3- to 12-membered heterocycloalkyl, the cycloalkyl and the heterocycloalkyl are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-6alkyl and C1-6haloalkyl, and when there are a plurality of Ra, these are the same as or different from each other;

[0030] R5are each independently selected from the group consisting of halogen, -CN, -NO2and -(C(Rx')2)f-Ry';

[0031] Rx'are each independently hydrogen, halogen, C1-3alkyl or C1-3haloalkyl;

[0032] f is an integer of 0 to 3;

[0033] Ry'is -Ra', -ORa', -SRa', -N(Ra')2, -CORa', -SO2Ra', -CO2Ra', -OCORa', -CON(Ra')2, -SO2N(Ra')2, -NHCORa'or -NHSO2Ra';

[0034] Ra'are each independently hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6aminoalkyl, C3-10cycloalkyl or 3- to 12-membered heterocycloalkyl, the cycloalkyl and the heterocycloalkyl are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-6alkyl and C1-6haloalkyl, and when there are a plurality of Ra', these are the same as or different from each other;

[0035] when there are two or more R5, the same or different R5optionally bond to each other to form 5- to 12-membered heteroaryl or 3- to 12-membered heterocycloalkyl together with atoms on ring C to which these bond, and herein, the heteroaryl or heterocycloalkyl is optionally substituted with 1 to 3 Rz;

[0036] Rzare each independently halogen, C1-3alkyl or C1-3haloalkyl;

[0037] n is an integer of 0 to 4; and

[0038] m and o are each independently an integer of 0 to 5.

[0039] According to one embodiment of the present disclosure, there may be provided a pharmaceutical composition including the compound described above; and one or more types of pharmaceutically acceptable carriers.

[0040] In the present specification, the term 'alkyl' means an aliphatic hydrocarbon radical, and includes both linear and branched hydrocarbon radicals. For example, C1-6alkyl is aliphatic hydrocarbon having 1 to 6 carbon atoms, and includes all of methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, neopentyl, isopentyl and the like.

[0041] In addition, the term 'hydroxy' is defined as -OH, and the term 'alkoxy' means a radical obtained by substituting a hydrogen atom of a hydroxy group with alkyl unless otherwise defined. For example, C1-6alkoxy includes all of methoxy, ethoxy, propoxy, n-butoxy, n-pentyloxy, isopropoxy, sec-butoxy, tert-butoxy, neopentyloxy, isopentyloxy and the like.

[0042] In addition, the term 'halogen' means fluorine, bromine, chlorine and iodine.

[0043] In addition, the term 'amino' is defined as -NH2, and the term 'alkylamino' means amino substituted with mono- or di-alkyl. For example, C1-6alkylamino includes amino substituted with mono- or di-C1-6alkyl.

[0044] In addition, the term 'haloalkyl' means alkyl substituted with one or more halogens, the term 'hydroxyalkyl' means alkyl substituted with one or more hydroxys, and the term 'aminoalkyl' means alkyl substituted with one or more aminos.

[0045] In addition, the term 'haloalkoxy' means alkoxy substituted with one or more halogens.

[0046] In addition, the term 'alkylthio' is defined as -SR (in the formula, R is alkyl).

[0047] In addition, the term 'cyano' is defined as -CN.

[0048] In addition, the term 'nitro' is defined as -NO2.

[0049] In addition, the term 'cycloalkyl' means cyclic alkyl, and herein the alkyl has the same definition as above. In addition, the cycloalkyl means a single ring, or a multiring such as a spiro ring, a bridged ring or a fused ring. In addition, the cycloalkyl may include one or more oxo (=O) or thioxo (=S) substituents. For example, the cycloalkyl includes C3-10cycloalkyl, C3-6cycloalkyl and the like. For example, the cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or the like, but is not limited thereto.

[0050] In addition, the term 'heterocycloalkyl' means cycloalkyl containing one or more heteroatoms (preferably, 1, 2, 3 or 4 heteroatoms) selected from among N, O or S. In addition, the heterocycloalkyl means a single ring, or a multiring such as a spiro ring, a bridged ring or a fused ring. In addition, the heterocycloalkyl means a saturated or partially unsaturated ring. In addition, the heterocycloalkyl may include one or more oxo (=O) or thioxo (=S) substituents. For example, the heterocycloalkyl includes 3- to 12-membered heterocycloalkyl, 3- to 7-membered heterocycloalkyl or the like. For example, the heterocycloalkyl includes azetidinyl, pyrrolidinyl, piperidinyl, pyrazolidinyl, morpholinyl, piperazinyl, tetrahydropyranyl, tetrahydrofuranyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, 2H-benzo[b][1,4]oxazin-3(4H)-onyl, hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl, hexahydropyrrolo[1,2-a]pyrazin-6(2H)-onyl, 2,6-diazaspiro[3.3]heptan-2-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl and the like, but are not limited thereto.

[0051] In addition, the term 'aryl' means an aromatic ring, and may be a single ring or a multiring. For example, the aryl includes 3- to 12-membered aryl, 6- to 12-membered aryl or the like. For example, the aryl includes phenyl, naphthyl, biphenyl and the like, but are not limited thereto.

[0052] In addition, the term 'heteroaryl' means an aromatic ring containing one or more heteroatoms (preferably, 1, 2, 3 or 4 heteroatoms) selected from among N, O or S, and may be a single ring or a multiring. For example, the heteroaryl includes 3- to 12-membered heteroaryl, 5- to 12-membered heteroaryl or the like. For example, the heteroaryl includes thiophenyl, furyl, pyrrolyl, pyrazolyl, thiazolyl, oxazolyl, pyridinyl, pyrimidyl, quinolinyl, quinazolinyl, quinoxalinyl, pteridinyl, pyrimidopyridinyl, pyridopyrazinyl, naphthyridinyl and the like, but are not limited thereto.

[0053] In addition, the term 'bicyclic fused-ring' means an aromatic or heteroaromatic ring structure in which two rings are fused through one or more shared atoms, and examples thereof include pteridine, pyridopyrimidine, pyridopyrazine, quinazoline, naphthyridine, quinoxaline and the like.

[0054] One embodiment of the present disclosure provides a compound selected from the group consisting of a compound represented by the following Chemical Formula 1, optical isomers thereof, solvates thereof, hydrates thereof, and pharmaceutically acceptable salts thereof:

[0055] [Chemical Formula 1]

[0056]

[0057] in Chemical Formula 1,

[0058] X1, X2, X3and X4are each independently N or CH, provided that at least two of X1to X4are N;

[0059] R1and R2are each independently hydrogen, halogen, C1-6alkyl or C1-6haloalkyl;

[0060] A is C6-12aryl or 5- to 12-membered heteroaryl;

[0061] B is C6-12aryl, 5- to 12-membered heteroaryl or 3- to 12-membered heterocycloalkyl;

[0062] C is C6-12aryl or 5- to 12-membered heteroaryl;

[0063] R3are each independently selected from the group consisting of halogen, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6aminoalkyl and C1-6haloalkoxy;

[0064] R4are each independently selected from the group consisting of halogen, -CN, -NO2and -(C(Rx)2)e-Ry;

[0065] Rxare each independently hydrogen, halogen, C1-3alkyl or C1-3haloalkyl;

[0066] e is an integer of 0 to 3;

[0067] Ryis -Ra, -ORa, -SRa, -N(Ra)2, -CORa, -SO2Ra, -CO2Ra, -OCORa, -CON(Ra)2, -SO2N(Ra)2, -NHCORaor -NHSO2Ra;

[0068] Raare each independently hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6aminoalkyl, C3-10cycloalkyl or 3- to 12-membered heterocycloalkyl, the cycloalkyl and the heterocycloalkyl are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-6alkyl and C1-6haloalkyl, and when there are a plurality of Ra, these are the same as or different from each other;

[0069] R5are each independently selected from the group consisting of halogen, -CN, -NO2and -(C(Rx')2)f-Ry';

[0070] Rx'are each independently hydrogen, halogen, C1-3alkyl or C1-3haloalkyl;

[0071] f is an integer of 0 to 3;

[0072] Ry'is -Ra', -ORa', -SRa', -N(Ra')2, -CORa', -SO2Ra', -CO2Ra', -OCORa', -CON(Ra')2, -SO2N(Ra')2, -NHCORa'or -NHSO2Ra';

[0073] Ra'are each independently hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6aminoalkyl, C3-10cycloalkyl or 3- to 12-membered heterocycloalkyl, the cycloalkyl and the heterocycloalkyl are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-6alkyl and C1-6haloalkyl, and when there are a plurality of Ra', these are the same as or different from each other;

[0074] when there are two or more R5, the same or different R5optionally bond to each other to form 5- to 12-membered heteroaryl or 3- to 12-membered heterocycloalkyl together with atoms on ring C to which these bond, and herein, the heteroaryl or heterocycloalkyl is optionally substituted with 1 to 3 Rz;

[0075] Rzare each independently halogen, C1-3alkyl or C1-3haloalkyl;

[0076] n is an integer of 0 to 4; and

[0077] m and o are each independently an integer of 0 to 5.

[0078] In one embodiment of the present disclosure, A may be phenyl or 5- or 6-membered heteroaryl.

[0079] In one embodiment of the present disclosure, the compound may be represented by any one of the following Chemical Formulae 2 to 6:

[0080] [Chemical Formula 2]

[0081]

[0082] [Chemical Formula 3]

[0083]

[0084] [Chemical Formula 4]

[0085]

[0086] [Chemical Formula 5]

[0087]

[0088] [Chemical Formula 6]

[0089]

[0090] in Chemical Formulae 2 to 6,

[0091] p is an integer of 0 to 4,

[0092] q is an integer of 0 to 3,

[0093] r is an integer of 0 to 2, and

[0094] X1to X4, R1, R2, R3, R4, R5, m and o have the same definitions as above.

[0095] In one embodiment of the present disclosure, R1and R2may be each independently hydrogen or C1-6alkyl.

[0096] In one embodiment of the present disclosure, R1and R2may be each independently C1-6alkyl.

[0097] In one embodiment of the present disclosure, R1and R2may all be methyl.

[0098] In one embodiment of the present disclosure, at least three of X1to X4may be N.

[0099] In one embodiment of the present disclosure, X1, X2and X4may be N.

[0100] In one embodiment of the present disclosure, X2, X3and X4may be N.

[0101] In one embodiment of the present disclosure, X1, X2, X3and X4may all be N.

[0102] In one embodiment of the present disclosure, B may be selected from among the following substituents:

[0103]

[0104] in the chemical formulae,

[0105] means a site where a bond is formed,

[0106] X5to X9are each independently N or C(R4),

[0107] Y1to Y6are each independently CO, C(R4)2, N(R4), O or S, and

[0108] R4has the same definition as above.

[0109] In one embodiment of the present disclosure, B may be selected from among the following substituents:

[0110]

[0111]

[0112]

[0113] in the chemical formulae,

[0114] means a site where a bond is formed,

[0115] s is an integer of 0 to 3,

[0116] t is an integer of 0 to 2,

[0117] u is an integer of 0 to 4,

[0118] v is an integer of 0 to 5, and

[0119] R4has the same definition as above.

[0120] In one embodiment of the present disclosure, B may be selected from among the following substituents:

[0121]

[0122] in the chemical formulae,

[0123] means a site where a bond is formed.

[0124] In one embodiment of the present disclosure,

[0125] R4are each independently -(C(Rx)2)e-Ry,

[0126] Rxare each independently hydrogen or C1-3alkyl,

[0127] e is an integer of 0 to 2,

[0128] Ryis -Ra, -ORa, -SRa, -N(Ra)2, -CORaor -CO2Ra,

[0129] Raare each independently hydrogen, C1-6alkyl, C3-10cycloalkyl or 3- to 12-membered heterocycloalkyl, the cycloalkyl and the heterocycloalkyl are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-6alkyl and C1-6haloalkyl, and when there are a plurality of Ra, these are the same as or different from each other; and

[0130] m may be an integer of 0 to 3.

[0131] In one embodiment of the present disclosure, C may be selected from among the following substituents:

[0132]

[0133] in the chemical formulae,

[0134] means a site where a bond is formed,

[0135] X10to X14are each independently N or C(R5),

[0136] Y7is N(R5), O or S, and

[0137] R5has the same definition as above.

[0138] In one embodiment of the present disclosure, C may be selected from among the following substituents:

[0139]

[0140] in the chemical formulae,

[0141] means a site where a bond is formed,

[0142] w is an integer of 0 to 2,

[0143] x is an integer of 0 to 5,

[0144] y is an integer of 0 to 4,

[0145] z is an integer of 0 to 3, and

[0146] R5has the same definition as above.

[0147] In one embodiment of the present disclosure, C may be selected from among the following substituents:

[0148]

[0149] in the chemical formulae,

[0150] means a site where a bond is formed.

[0151] In one embodiment of the present disclosure,

[0152] R5are each independently selected from the group consisting of halogen, -CN, -NO2and -Ry',

[0153] Ry'is -Ra', -ORa', -SRa', -N(Ra')2, -CORa', -CO2Ra', -OCORa', -CON(Ra')2, -SO2N(Ra')2or -NHCORa',

[0154] Ra'are each independently hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6aminoalkyl, C3-10cycloalkyl or 3- to 12-membered heterocycloalkyl, the cycloalkyl and the heterocycloalkyl are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-6alkyl and C1-6haloalkyl, and when there are a plurality of Ra', these are the same as or different from each other;

[0155] when there are two or more R5, the same or different R5optionally bond to each other to form 5- to 12-membered heteroaryl or 3- to 12-membered heterocycloalkyl together with atoms on ring C to which these bond, and herein, the heteroaryl or heterocycloalkyl is optionally substituted with 1 to 3 Rz;

[0156] Rzare each independently halogen, C1-3alkyl or C1-3haloalkyl, and

[0157] o may be an integer of 1 to 4.

[0158] One embodiment of the present disclosure provides a compound selected from the group consisting of a compound selected from the group consisting of the following compounds, an optical isomer thereof, a solvate thereof, a hydrate thereof, and a pharmaceutically acceptable salt thereof:

[0159] 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0160] 4-(2,4-difluoro-5-methylphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0161] 4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0162] 4-(5-chloro-2,4-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0163] 6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(2,4,5-trifluorophenyl)pteridine

[0164] 6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(2,3,4-trifluorophenyl)pteridine

[0165] 4-(2,4-difluoro-3-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0166] 4-(3-chloro-2,4-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0167] 4-(2,4-difluoro-3-methylphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0168] 4-(2,4-difluoro-3-methoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0169] 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0170] 4-(2-fluoro-4-(methylthio)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0171] 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0172] 4-(2-fluoro-4-methoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0173] N-cyclopropyl-4-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluoro-N-methylbenzenesulfonamide

[0174] 4-(2-fluoro-4-isopropoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0175] 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0176] 4-(2,4-difluoro-5-methylphenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0177] 4-(4-chloro-2,3-difluoro-5-methoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0178] 4-(5-chloro-2,4-difluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0179] 4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0180] 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0181] 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0182] 4-(4-chloro-2-fluorophenyl)-2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0183] 4-(4-chloro-2-fluorophenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0184] 4-(2-fluoro-4-methylphenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0185] 4-(2-fluoro-4-methylphenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0186] 2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine

[0187] 4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0188] 4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0189] 4-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0190] 4-(2,5-difluoropyridin-4-yl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0191] 6-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine

[0192] 6-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-7-fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one

[0193] 6-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-5-fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one

[0194] 4-(8-fluoroquinolin-7-yl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0195] 4-(4-chloro-2-fluorophenyl)-2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0196] 4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine

[0197] 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine

[0198] 2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine

[0199] 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine

[0200] (3-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-2,6-difluorophenyl)methanol

[0201] 6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(2,3,4-trifluoro-5-methylphenyl)pteridine

[0202] 4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine

[0203] 2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine

[0204] 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine

[0205] 4-(2-fluoro-3-methoxy-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0206] 4-(2,3-difluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0207] 4-(5-chloro-2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0208] 5-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-2-(trifluoromethyl)thiazole

[0209] 6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pteridine

[0210] 3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0211] 4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0212] 4-(6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0213] 4-(6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0214] 4-(4-chloro-2-fluorophenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0215] 2-([3,4-bipyridin]-5-yl)-4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridine

[0216] 4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0217] 4-(2,3-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0218] 4-(2,5-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0219] 4-(3,5-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0220] 4-(2,4-difluorophenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0221] 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine

[0222] 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine

[0223] 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0224] 4-(6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridin-4-yl)-3-fluorobenzonitrile

[0225] 4-(2,4-difluorophenyl)-2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0226] 4-(2,4-difluorophenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0227] 4-(2,4-difluorophenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0228] 2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-4-(2,4-difluorophenyl)-6,7-dimethylpteridine

[0229] 4-(2,4-difluorophenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0230] 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine

[0231] 2-([3,4-bipyridin]-5-yl)-4-(2,4-difluorophenyl)-6,7-dimethylpteridine

[0232] 4-(4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorophenyl)morpholine

[0233] 4-(3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)phenyl)morpholine

[0234] 4-(4-(6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridin-4-yl)-3-fluorophenyl)morpholine

[0235] 4-(4-chloro-2-fluorophenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0236] 4-(4-chloro-2-fluorophenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0237] 2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine

[0238] 4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzamide

[0239] 3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzamide

[0240] 4-fluoro-3-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzamide

[0241] 4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluoro-N,N-dimethylaniline

[0242] 3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)-N,N-dimethylaniline

[0243] 4-(6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridin-4-yl)-3-fluoro-N,N-dimethylaniline

[0244] 4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine

[0245] 4-(2-fluoro-4-methylphenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0246] 4-(2-fluoro-4-methylphenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0247] 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine

[0248] 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine

[0249] 2-([3,4-bipyridin]-5-yl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine

[0250] 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0251] 4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0252] 4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0253] 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine

[0254] 2-([3,4-bipyridin]-5-yl)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine

[0255] 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0256] 2-([2,4-bipyridin]-4-yl)-4-(2,4-difluorophenyl)-6,7-dimethylpteridine

[0257] 4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0258] 4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine

[0259] 4-(6,7-dimethyl-2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0260] 4-(6,7-dimethyl-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0261] 2-([2,4-bipyridin]-4-yl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine

[0262] 4-(2-fluoro-4-chlorophenyl)-6,7-dimethyl-2-(3-trifluoromethyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0263] 4-(6,7-dimethyl-2-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0264] 4-(6,7-dimethyl-2-(3-trifluoromethyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0265] 4-(6,7-dimethyl-2-(3-(4-methylpiperazin-1-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0266] 4-(2-fluoro-4-nitrophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0267] 4-(6,7-dimethyl-2-(3-methyl-5-(2-methylpyridin-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0268] 2-([2,4-bipyridin]-4-yl)-4-(2-fluoro-4-chlorophenyl)-6,7-dimethylpteridine

[0269] 4-[4-(difluoromethyl)-2-fluorophenyl]-6,7-dimethyl-2-[3-methyl-5-(pyridin-4-yl)phenyl]pteridine

[0270] 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(tetrahydrofuran-3-yl)phenyl)pteridine

[0271] 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(tetrahydro-2H-pyran-4-yl)phenyl)pteridine

[0272] 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0273] 4-(6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridin-4-yl)-3-fluorobenzonitrile

[0274] 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0275] 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-methyl-1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0276] 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0277] 4-(2-fluoro-4-chlorophenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0278] 4-(2-fluoro-4-chlorophenyl)-6,7-dimethyl-2-(3-methyl-1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0279] 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0280] 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(2-methylpyridin-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0281] 4-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpyrido[2,3-d]pyrimidin-2-yl)-5-fluorophenyl)morpholine

[0282] 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0283] 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(2-methylpyridin-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0284] (4-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-1H-pyrazol-1-yl)(1-methylpiperidin-4-yl)methanone

[0285] 1-(4-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)phenyl)piperazin-1-yl)ethan-1-one

[0286] 3-fluoro-4-(2-(3-fluoro-5-(2-methylpyridin-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidin-4-yl)benzonitrile

[0287] 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0288] 3-fluoro-4-(2-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0289] 3-fluoro-4-(2-(3-fluoro-4-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0290] 4-(4-(difluoromethyl)-2-fluorophenyl)-2-(3-fluoro-5-(4-(2-methoxyethyl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0291] 3-fluoro-4-(2-(3-fluoro-5-(4-isobutyrylpiperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0292] 4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0293] 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-((1-methylazetidin-3-yl)methyl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0294] 3-fluoro-4-(2-(3-fluoro-5-(4-((1-methylazetidin-3-yl)methyl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0295] 2-(4-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)piperazin-1-yl)-N,N-dimethylethan-1-amine

[0296] 3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylpiperidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0297] tert-butyl (3S,5R)-4-(3-(4-(4-cyano-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-3,5-dimethylpiperazine-1-carboxylate

[0298] 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0299] 3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0300] 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(4-(pyridin-4-yl)-1H-pyrazol-1-yl)pteridine

[0301] 8-(2,4-difluorophenyl)-2,3-dimethyl-6-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazine

[0302] 8-(4-chloro-2-fluorophenyl)-6-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-2,3-dimethylpyrido[2,3-b]pyrazine

[0303] 4-(2-(3-(1-acetylpiperidin-3-yl)-5-methylphenyl)-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile

[0304] 4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(2-methyl-6-(4-methylpiperazin-1-yl)pyridin-4-yl)pteridine

[0305] 4-(2-(3-(1-acetylpyrrolidin-3-yl)-5-methylphenyl)-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile

[0306] 1-(5-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)ethan-1-one

[0307] 1-(3-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)piperidin-1-yl)ethan-1-one

[0308] 3-fluoro-4-(2-(3-methyl-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0309] 2-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)phenyl)hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one

[0310] 4-(2-(3-(1-acetylpyrrolidin-3-yl)-5-fluorophenyl)-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile

[0311] 4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(4-methylpiperazin-1-yl)phenyl)pteridine

[0312] 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(1-methylpyrrolidin-3-yl)phenyl)-6,7-dimethylpteridine

[0313] 1-(6-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-2,6-diazaspiro[3.3]heptan-2-yl)-3,3-dimethylbutan-1-one

[0314] 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(6-isopropyl-2,6-diazaspiro[3.3]heptan-2-yl)phenyl)-6,7-dimethylpteridine

[0315] 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(1-isopropylpiperidin-4-yl)phenyl)-6,7-dimethylpteridine

[0316] 1-(4-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)piperidin-1-yl)ethan-1-one

[0317] 3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylazetidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0318] 4-(6,7-dimethyl-2-(3-morpholino-5-(trifluoromethyl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0319] 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(5-isopropyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-6,7-dimethylpteridine

[0320] 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-isopropylpiperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0321] 1-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-N,N-dimethylazetidin-3-amine

[0322] 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(4-(2-methylpyridin-4-yl)-1H-pyrazol-1-yl)pteridine

[0323] 3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylpyrrolidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0324] 4-(6,7-dimethyl-2-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0325] 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-(1-methylazetidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0326] 1-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-N,N-dimethylazetidin-3-amine

[0327] 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-(1-methylpyrrolidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0328] 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0329] 4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(4-(1-methylazetidin-3-yl)piperazin-1-yl)phenyl)pteridine

[0330] 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(4-(1-isopropylpyrrolidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0331] The compound of Chemical Formula 1 of the present disclosure or a pharmaceutically acceptable salt thereof may be present as a structural isomer such as a tautomer, an R or S isomer having an asymmetric carbon center, a stereoisomer such as a geometric isomer (trans, cis), or an optical isomer (enantiomer). Accordingly, unless otherwise indicated, the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof may include all of cis or trans, optical isomers such as (R) or (S), and racemates (RS).

[0332] The compound of Chemical Formula 1 of the present disclosure may have a form of a pharmaceutically acceptable salt. The salt may include common acid addition salts, for example, salts derived from inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid and bromic acid, and salts derived from organic acids 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 and acetylsalicylic acid. In addition, the salt includes salts derived from amino acids such as glycine, alanine, valine, isoleucine, serine, cysteine, cystine, asparaginic acid, glutamine, lysine, arginine, tyrosine and proline. In addition, the salt includes salts of sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid and toluenesulfonic acid.

[0333] The compound of Chemical Formula 1 according to the present disclosure or a pharmaceutically acceptable salt thereof may have a solvated form. The term 'solvate' in the present specification means a molecular complex including the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable solvent molecules. The term 'hydrate' means that the solvent is water.

[0334] The compound of Chemical Formula 1 according to the present disclosure or a pharmaceutically acceptable salt thereof may be prepared using various methods. For example, the compound of Chemical Formula 1 according to the present disclosure or a pharmaceutically acceptable salt thereof may be prepared using a preparation method including: reacting a compound of Chemical Formula A with a compound of Chemical Formula B-1 or Chemical Formula B-2 to prepare the compound of Chemical Formula 1; and converting the compound of Chemical Formula 1 into a pharmaceutically acceptable salt thereof.

[0335] [Chemical Formula 1]

[0336]

[0337] [Chemical Formula A]

[0338]

[0339] [Chemical Formula B-1]

[0340]

[0341] [Chemical Formula B-2]

[0342]

[0343] In Chemical Formulae 1, A, B-1 and B-2, A, B, C, X1, X2, X3, X4, R1, R2, R3, R4, R5, m, n and o have the same definitions as above.

[0344] The reaction between the compound of Chemical Formula A and the commercially available compound of Chemical Formula B-1 or Chemical Formula B-2 may be performed through a Suzuki reaction. The reaction may be performed using a palladium catalyst, and the palladium catalyst includes palladium diacetate (Pd(OAc)2), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (Pd(dppf)Cl2·CH2Cl2), palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride (PdCl2(dppf)2) or the like. When performing the reaction under the palladium catalyst, a ligand and a base may be added in addition to the palladium catalyst. The ligand includes (S)-2,2-bis(diphenylphosphino)-1,1-binaphthyl (BINAP), 1,1'-bis(diphenylphosphino)ferrocene (dppf), (tri-o-tolyl)phosphine (P(o-Tol)3) or the like, and the base includes an inorganic base such as cesium carbonate (Cs2CO3), sodium carbonate (Na2CO3), potassium carbonate (K2CO3), potassium fluoride (KF), cesium fluoride (CsF), sodium hydroxide (NaOH), potassium phosphonate (K3PO4), sodium tert-butoxide (tert-BuONa) or potassium tert-butoxide (tert-BuOK). The reaction may be performed at 50°C to 150°C, preferably at 80°C to 110°C, in a non-polar organic solvent such as benzene or toluene, or a polar organic solvent such as dioxane, tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane orN,N-dimethylformamide. Other reaction conditions including the reaction time may be determined according to a known method on the Suzuki reaction [Barbara Czako and Laszlo Kurti, STRATEGIC APPLICATIONS of NAMED REACTIONS in ORGANIC SYNTHESIS, 2005].

[0345] The compound of Chemical Formula A may be prepared using a preparation method of the following Reaction Formula 1.

[0346] [Reaction Formula 1]

[0347]

[0348] In Reaction Formula 1, C, X1, X2, X3, X4, R1, R2, R5and o have the same definitions as above.

[0349] The compounds of Chemical Formulae C, D-1 and D-2 are commercially available. The coupling reaction between the compound of Chemical Formula C and the compound of Chemical Formula D-1 or Chemical Formula D-2 may be performed in the presence of a base and a solvent. The base may be cesium carbonate, potassium carbonate, sodium carbonate or the like, and the solvent may be an organic solvent such asN,N-dimethylformamide, dioxane or tetrahydrofuran. In addition, the reaction may be performed at room temperature to 100°C.

[0350] The bicyclic fused-ring derivative according to the present disclosure, that is, the compound of Chemical Formula 1, or a pharmaceutically acceptable salt thereof may be useful in treatment of TREM2-mediated degenerative brain diseases by inducing TREM2 activation. Preferably, the compound of Chemical Formula 1 according to the present disclosure or a pharmaceutically acceptable salt thereof may be useful in preventing or treating various neurodegenerative diseases such as Alzheimer's disease, frontotemporal lobar degeneration (FTLD), FTLD-like syndrome, Parkinson's disease, Huntington's disease, Nasu-Hakola disease, multiple sclerosis, Guillain-Barr syndrome, chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis (ALS), rheumatoid arthritis, prion disease, or stroke.

[0351] Accordingly, the present disclosure includes a pharmaceutical composition inducing activation of TREM2, the composition including a therapeutically effective amount of the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. In one embodiment, the present disclosure provides a pharmaceutical composition for preventing or treating Alzheimer's disease, frontotemporal lobar degeneration (FTLD), FTLD-like syndrome, Parkinson's disease, Huntington's disease, Nasu-Hakola disease, multiple sclerosis, Guillain-Barr syndrome, chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis (ALS), rheumatoid arthritis, prion disease, or stroke, the composition including a therapeutically effective amount of the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0352] The pharmaceutical composition of the present disclosure may include a commonly used pharmaceutically acceptable carrier such as an excipient, a disintegrant, a sweetener, a lubricant or a flavoring agent, and may be formulated into oral preparations such as tablets, capsules, powders, granules, suspensions, emulsions or syrups; or parenteral preparations such as external solutions, external suspensions, external emulsions, gels (ointments or the like), inhalants, sprays or injections using common methods. The formulation may be formulated into various forms such as single-dose or multiple-dose dosage forms.

[0353] The pharmaceutical composition of the present disclosure may include an excipient such as lactose or corn starch, a lubricant such as magnesium stearate, an emulsifier, a suspension, a stabilizing agent, an isotonic agent and the like. When necessary, a sweetener and / or a flavoring agent may be added thereto.

[0354] The composition of the present disclosure may be administered orally, or parenterally including methods of inhalation, intravenous, intraperitoneal, subcutaneous, rectal and topical administration. Accordingly, the composition of the present disclosure may be formulated into various forms such as tablets, capsules, aqueous solutions or suspensions. In the case of oral tablets, a carrier such as lactose or corn starch, and a lubricant such as magnesium stearate may be commonly added thereto. In the case of capsules for oral administration, lactose and / or dry corn starch may be used as a diluent. When an oral aqueous suspension is required, the active ingredient may be combined with an emulsifier and / or a suspending agent. When necessary, a specific sweetener and / or a flavoring agent may be added. For intramuscular, intraperitoneal, subcutaneous and intravenous administration, a sterile solution of the active ingredient is usually prepared, and the pH of the solution needs to be properly adjusted and buffered. For intravenous administration, the total concentration of the solute needs to be adjusted so that isotonicity is provided to the formulation. The composition according to the present disclosure may have a form of an aqueous solution including a pharmaceutically acceptable carrier such as saline having a pH of 7.4. The solution may be introduced into the intramuscular blood stream of a patient by local bolus injection.

[0355] The term "therapeutically effective amount" used in the present disclosure refers to an amount of the compound represented by Chemical Formula 1 effective in treatment or prevention of TREM2-mediated degenerative brain diseases. For example, the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof may be administered to a patient in an effective dose of about 0.001 mg / kg to about 100 mg / kg per day. The dosage may be changed for sure depending on the age, weight, sensitivity or symptoms of a patient, or efficacy of the compound.

[0356] The present disclosure also includes a method for inducing activation of TREM2 in a mammal, the method including administering a therapeutically effective amount of the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof to a mammal. In one embodiment, the present disclosure provides a method for preventing or treating Alzheimer's disease, frontotemporal lobar degeneration (FTLD), FTLD-like syndrome, Parkinson's disease, Huntington's disease, Nasu-Hakola disease, multiple sclerosis, Guillain-Barr syndrome, chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis (ALS), rheumatoid arthritis, prion disease, or stroke, the method including administering a therapeutically effective amount of the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof to a mammal.

[0357] The present disclosure provides a use of the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof in the manufacture of drugs inducing activation of TREM2 in a mammal. In one embodiment, the present disclosure provides a use of the compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof in the manufacture of drugs for preventing or treating Alzheimer's disease, frontotemporal lobar degeneration (FTLD), FTLD-like syndrome, Parkinson's disease, Huntington's disease, Nasu-Hakola disease, multiple sclerosis, Guillain-Barr syndrome, chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis (ALS), rheumatoid arthritis, prion disease, or stroke.

[0358] Hereinafter, the present disclosure will be described in more detail with reference to examples and experimental examples. However, these examples and experimental examples are for illustrative purposes only, and the present disclosure is not limited thereto.

[0359] Compounds prepared in the following examples were analyzed as follows: Nuclear magnetic resonance (NMR) spectrum analysis was performed using a Bruker 400 MHz spectrometer, and chemical shifts were analyzed in ppm. In addition, the molecular weight represented by ESI+ (indicating an m / z value in ESI-MS (cation), and indicating a [M+H]+ peak) was measured using an Agilent 1260 Infinity series liquid chromatography / mass selective detector (MSD, single quadrupole) equipped with an electrostatic spray interface. Column chromatography was performed on silica gel (Merck, 70 to 230 mesh) [W.C. Still, J. Org. Chem., 43, 2923, 1978]. In addition, abbreviations used in the following examples are as follows: methyl is abbreviated as Me, ethyl is abbreviated as Et, and phenyl is abbreviated as Ph. In addition, starting materials of each example are known compounds, and were either synthesized according to literatures, or purchased from reagent companies such as Sigma-Aldrich.

[0360] The following reference examples represent methods for synthesizing intermediates for preparing the compounds of the present disclosure or salts thereof (that is, compounds of examples).

[0361] Reference Example 1. Preparation of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine

[0362] 2,4-dichloro-6,7-dimethylpteridine (200 mg) and 2,4-difluorophenylboronic acid (193 mg) were dissolved in dioxane (4.0 mL) and purified water (1.0 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (35.6 mg) and cesium carbonate (570 mg) thereto, the mixture was stirred for 1 hour at 50°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 1) to prepare the title compound (85 mg, yield: 31.7%). LC / MS (ESI+) m / z [M+H]+: 307.0

[0363] Reference Example 2. Preparation of 2-chloro-4-(2,4-difluoro-5-methylphenyl)-6,7-dimethylpteridine

[0364] The title compound (91 mg, yield: 32.3%) was prepared in the same manner as in Reference Example 1, except that 2,4-difluoro-5-methylphenylboronic acid (210 mg) was used instead of 2,4-difluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 321.0

[0365] Reference Example 3. Preparation of 2-chloro-4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridine

[0366] 2,4-dichloro-6,7-dimethylpteridine (50 mg) and 4-chloro-2-fluorophenylboronic acid (38 mg) were dissolved in dioxane (2.0 mL) and purified water (0.2 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (17.8 mg) and cesium carbonate (213.4 mg) thereto, the mixture was stirred for 1 hour at 90°C. The reaction mixture was cooled to room temperature, and, after adding dichloromethane thereto, washed with a saturated aqueous ammonium chloride solution, and dried with anhydrous sodium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=6 / 1) to prepare the title compound (33 mg, yield: 46.8%). LC / MS (ESI+) m / z [M+H]+: 325.0

[0367] Reference Example 4. Preparation of 2-chloro-4-(5-chloro-2,4-difluorophenyl)-6,7-dimethylpteridine

[0368] The title compound (46 mg, yield: 61.8%) was prepared in the same manner as in Reference Example 3, except that 5-chloro-2,4-difluorophenylboronic acid (42 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 337.0

[0369] Reference Example 5. Preparation of 2-chloro-6,7-dimethyl-4-(2,4,5-trifluorophenyl)pteridine

[0370] The title compound (45 mg, yield: 63.5%) was prepared in the same manner as in Reference Example 3, except that 2,4,5-trifluorophenylboronic acid (38.4 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 325.0

[0371] Reference Example 6. Preparation of 2-chloro-6,7-dimethyl-4-(2,3,4-trifluorophenyl)pteridine

[0372] The title compound (49 mg, yield: 69.1%) was prepared in the same manner as in Reference Example 3, except that 2,3,4-trifluorophenylboronic acid (38.4 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 325.1

[0373] Reference Example 7. Preparation of 2-chloro-4-(2,4-difluoro-3-(trifluoromethyl)phenyl)-6,7-dimethylpteridine

[0374] The title compound (40 mg, yield: 48.9%) was prepared in the same manner as in Reference Example 3, except that 2,4-difluoro-3-(trifluoromethyl)phenylboronic acid (49.3 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 375.1

[0375] Reference Example 8. Preparation of 2-chloro-4-(3-chloro-2,4-difluorophenyl)-6,7-dimethylpteridine

[0376] The title compound (33 mg, yield: 44.3%) was prepared in the same manner as in Reference Example 3, except that 3-chloro-2,4-difluorophenylboronic acid (42 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 341.0

[0377] Reference Example 9. Preparation of 2-chloro-4-(2,4-difluoro-3-methylphenyl)-6,7-dimethylpteridine

[0378] The title compound (46 mg, yield: 65.7%) was prepared in the same manner as in Reference Example 3, except that 2,4-difluoro-3-methylphenylboronic acid (37.5 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 321.0

[0379] Reference Example 10. Preparation of 2-chloro-4-(2,4-difluoro-3-methoxyphenyl)-6,7-dimethylpteridine

[0380] The title compound (37 mg, yield: 50.3%) was prepared in the same manner as in Reference Example 3, except that 2,4-difluoro-3-methoxyphenylboronic acid (41 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 337.1

[0381] Reference Example 11. Preparation of 2-chloro-4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine

[0382] The title compound (45 mg, yield: 57.8%) was prepared in the same manner as in Reference Example 3, except that 2-fluoro-4-(trifluoromethyl)phenylboronic acid (45.4 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 357.0

[0383] Reference Example 12. Preparation of 2-chloro-4-(2-fluoro-4-(methylthio)phenyl)-6,7-dimethylpteridine

[0384] The title compound (37 mg, yield: 56.0%) was prepared in the same manner as in Reference Example 3, except that 2-fluoro-4-(methylthio)phenylboronic acid (40.6 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 335.1

[0385] Reference Example 13. Preparation of 2-chloro-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine

[0386] The title compound (33 mg, yield: 45.2%) was prepared in the same manner as in Reference Example 3, except that 2-fluoro-4-methylphenylboronic acid (33.6 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 303.0

[0387] Reference Example 14. Preparation of 2-chloro-4-(2-fluoro-4-methoxyphenyl)-6,7-dimethylpteridine

[0388] The title compound (45 mg, yield: 64.7%) was prepared in the same manner as in Reference Example 3, except that 2-fluoro-4-methoxyphenylboronic acid (37.1 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 319.0

[0389] Reference Example 15. Preparation of 4-(2-chloro-6,7-dimethylpteridin-4-yl)-N-cyclopropyl-3-fluoro-N-methylbenzenesulfonamide

[0390] The title compound (40 mg, yield: 43.4%) was prepared in the same manner as in Reference Example 3, except that (4-(N-cyclopropyl-N-methylsulfamoyl)-2-fluorophenyl)boronic acid (59.6 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 422.1

[0391] Reference Example 16. Preparation of 2-chloro-4-(2-fluoro-4-isopropoxyphenyl)-6,7-dimethylpteridine

[0392] The title compound (33 mg, yield: 43.6%) was prepared in the same manner as in Reference Example 3, except that 2-fluoro-4-isopropoxyphenylboronic acid (43.2 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 347.1

[0393] Reference Example 17. Preparation of 2-chloro-4-(4-chloro-2,3-difluoro-5-methoxyphenyl)-6,7-dimethylpteridine

[0394] The title compound (19 mg, yield: 23.5%) was prepared in the same manner as in Reference Example 3, except that 4-chloro-2,3-difluoro-5-methoxyphenylboronic acid (48.5 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 371.1

[0395] Reference Example 18. Preparation of 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile

[0396] 2,4-dichloro-6,7-dimethylpteridine (500 mg) and 4-cyano-2-fluorophenylboronic acid (360 mg) were dissolved in dioxane (10.0 mL) and purified water (2.0 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (89.1 mg) and cesium carbonate (2.1 g) thereto, the mixture was stirred for 1 hour at 50°C. The reaction mixture was cooled to room temperature, and, after adding dichloromethane thereto, dried with anhydrous sodium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 1) to prepare the title compound (100 mg, yield: 14.6%). LC / MS (ESI+) m / z [M+H]+: 314.0

[0397] Reference Example 19. Preparation of 2-chloro-4-(2,5-difluoropyridin-4-yl)-6,7-dimethylpteridine

[0398] 2,4-dichloro-6,7-dimethylpteridine (300 mg) and 2,5-difluoropyridine-4-boronic acid (291.3 mg) were dissolved in dioxane (10.0 mL) and purified water (2.0 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (53.5 mg) and cesium carbonate (1.3 g) thereto, the mixture was stirred for 1 hour at 50°C. The reaction mixture was cooled to room temperature, and, after adding dichloromethane thereto, dried with anhydrous sodium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 1) to prepare the title compound (20 mg, yield: 5.0%). LC / MS (ESI+) m / z [M+H]+: 308.0

[0399] Reference Example 20. Preparation of 6-(2-chloro-6,7-dimethylpteridin-4-yl)-7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine

[0400] The title compound (40 mg, yield: 8.8%) was prepared in the same manner as in Reference Example 19, except that (7-fluoro-3,4-dihydro-2H-1,4-benzoxazin-6-yl)boronic acid (361.1 mg) was used instead of 2,5-difluoropyridine-4-boronic acid. LC / MS (ESI+) m / z [M+H]+: 346.0

[0401] Reference Example 21. Preparation of 6-(2-chloro-6,7-dimethylpteridin-4-yl)-7-fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one

[0402] The title compound (70 mg, yield: 14.9%) was prepared in the same manner as in Reference Example 19, except that 7-fluoro-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-boronic acid pinacol ester (537.4 mg) was used instead of 2,5-difluoropyridine-4-boronic acid. LC / MS (ESI+) m / z [M+H]+: 360.1

[0403] Reference Example 22. Preparation of 6-(2-chloro-6,7-dimethylpteridin-4-yl)-5-fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one

[0404] The title compound (90 mg, yield: 19.1%) was prepared in the same manner as in Reference Example 19, except that 5-fluoro-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-boronic acid pinacol ester (537.4 mg) was used instead of 2,5-difluoropyridine-4-boronic acid. LC / MS (ESI+) m / z [M+H]+: 360.1

[0405] Reference Example 23. Preparation of 2-chloro-4-(8-fluoroquinolin-7-yl)-6,7-dimethylpteridine

[0406] The title compound (96 mg, yield: 21.6%) was prepared in the same manner as in Reference Example 19, except that 8-fluoro-quinolin-7-yl boronic acid pinacol ester (500.8 mg) was used instead of 2,5-difluoropyridine-4-boronic acid. LC / MS (ESI+) m / z [M+H]+: 340.0

[0407] Reference Example 24. Preparation of (3-(2-chloro-6,7-dimethylpteridin-4-yl)-2,6-difluorophenyl)methanol

[0408] The title compound (38 mg, yield: 49.3%) was prepared in the same manner as in Reference Example 3, except that [2,4-difluoro-3-(hydroxymethyl)phenyl]boronic acid (41.0 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 337.1

[0409] Reference Example 25. Preparation of 2-chloro-6,7-dimethyl-4-(2,3,4-trifluoro-5-methylphenyl)pteridine

[0410] The title compound (34 mg, yield: 46.0%) was prepared in the same manner as in Reference Example 3, except that (2,3,4-trifluoro-5-methyl)phenylboronic acid (45.4 mg) was used instead of 4-chloro-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 339.0

[0411] Reference Example 26. Preparation of 2-chloro-4-(2-fluoro-3-methoxy-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine

[0412] 2,4-dichloro-6,7-dimethylpteridine (200 mg) and 2-fluoro-3-methoxy-4-(trifluoromethyl)phenylboronic acid pinacol ester (237.9 mg) were dissolved in dioxane (3.6 mL) and purified water (0.7 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (35.7 mg) and cesium carbonate (853.4 mg) thereto, the mixture was stirred for 1 hour at 50°C. The reaction mixture was cooled to room temperature, and, after adding dichloromethane thereto, dried with anhydrous sodium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 1) to prepare the title compound (55 mg, yield: 16.3%). LC / MS (ESI+) m / z [M+H]+: 387.1

[0413] Reference Example 27. Preparation of 2-chloro-4-(2,3-difluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine

[0414] The title compound (30 mg, yield: 9.2%) was prepared in the same manner as in Reference Example 26, except that 2,3-difluoro-4-(trifluoromethyl)phenylboronic acid (197.2 mg) was used instead of 2-fluoro-3-methoxy-4-(trifluoromethyl)phenylboronic acid pinacol ester. LC / MS (ESI+) m / z [M+H]+: 375.1

[0415] Reference Example 28. Preparation of 2-chloro-4-(5-chloro-2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine

[0416] The title compound (30 mg, yield: 8.8%) was prepared in the same manner as in Reference Example 26, except that 5-chloro-2-fluoro-4-(trifluoromethyl)phenylboronic acid (242.4 mg) was used instead of 2-fluoro-3-methoxy-4-(trifluoromethyl)phenylboronic acid pinacol ester. LC / MS (ESI+) m / z [M+H]+: 391.0

[0417] Reference Example 29. Preparation of 5-(2-chloro-6,7-dimethylpteridin-4-yl)-2-(trifluoromethyl)thiazole

[0418] The title compound (50 mg, yield: 16.6%) was prepared in the same manner as in Reference Example 26, except that 2-trifluoromethylthiazol-5-yl boronic acid pinacol ester (341.1 mg) was used instead of 2-fluoro-3-methoxy-4-(trifluoromethyl)phenylboronic acid pinacol ester. LC / MS (ESI+) m / z [M+H]+: 346.1

[0419] Reference Example 30. Preparation of 2-chloro-6,7-dimethyl-4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pteridine

[0420] The title compound (30 mg, yield: 10.0%) was prepared in the same manner as in Reference Example 26, except that 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)-1H-pyrazole (340 mg) was used instead of 2-fluoro-3-methoxy-4-(trifluoromethyl)phenylboronic acid pinacol ester. LC / MS (ESI+) m / z [M+H]+: 345.0

[0421] Reference Example 31. Preparation of 2-chloro-4-(2,3-difluorophenyl)-6,7-dimethylpteridine

[0422] The title compound (110 mg, yield: 41%) was prepared in the same manner as in Reference Example 1, except that 2,3-difluorophenylboronic acid (193 mg) was used instead of 2,4-difluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 307.0

[0423] Reference Example 32. Preparation of 2-chloro-4-(2,5-difluorophenyl)-6,7-dimethylpteridine

[0424] The title compound (93.8 mg, yield: 35%) was prepared in the same manner as in Reference Example 1, except that 2,5-difluorophenylboronic acid (193 mg) was used instead of 2,4-difluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 307.0

[0425] Reference Example 33. Preparation of 2-chloro-4-(3,5-difluorophenyl)-6,7-dimethylpteridine

[0426] The title compound (96.5 mg, yield: 36%) was prepared in the same manner as in Reference Example 1, except that 3,5-difluorophenylboronic acid (193 mg) was used instead of 2,4-difluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 307.0

[0427] Reference Example 34. Preparation of 4-(4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorophenyl)morpholine

[0428] The title compound (136 mg, yield: 16.7%) was prepared in the same manner as in Reference Example 18, except that 2-fluoro-4-morpholinophenylboronic acid (687.6 mg) was used instead of 4-cyano-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 374.1

[0429] Reference Example 35. Preparation of 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorobenzamide

[0430] The title compound (60 mg, yield: 8.3%) was prepared in the same manner as in Reference Example 18, except that 4-carbamoyl-2-fluorophenylboronic acid (559.0 mg) was used instead of 4-cyano-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 332.1

[0431] Reference Example 36. Preparation of 3-(2-chloro-6,7-dimethylpteridin-4-yl)-4-fluorobenzamide

[0432] The title compound (72 mg, yield: 9.9%) was prepared in the same manner as in Reference Example 18, except that 5-carbamoyl-2-fluorophenylboronic acid (559.0 mg) was used instead of 4-cyano-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 332.1

[0433] Reference Example 37. Preparation of 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluoro-N,N-dimethylaniline

[0434] 2,4-dichloro-6,7-dimethylpteridine (1.0 g) and 4-dimethylamino-2-fluorophenylboronic acid (958.6 mg) were dissolved in dioxane (18.0 mL) and purified water (3.5 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (178.3 mg) and cesium carbonate (4.3 g) thereto, the mixture was stirred for 1 hour at 50°C. The reaction mixture was cooled to room temperature, and, after adding dichloromethane thereto, dried with anhydrous sodium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 1) to prepare the title compound (570 mg, yield: 39.4%). LC / MS (ESI+) m / z [M+H]+: 332.1

[0435] Reference Example 38. Preparation of 2-chloro-4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-6,7-dimethylpteridine

[0436] The title compound (110 mg, yield: 17.2%) was prepared in the same manner as in Reference Example 18, except that 4-fluoro-1-methyl-5-(tetramethyl-1,3,2-dioxoborolan-2-yl)-1H-pyrazole (690.8 mg) was used instead of 4-cyano-2-fluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 293.1

[0437] Reference Example 39. Preparation of 2-chloro-4-(2-fluoro-4-nitrophenyl)-6,7-dimethylpteridine

[0438] The title compound (50 mg, yield: 11.4%) was prepared in the same manner as in Reference Example 1, except that 2-fluoro-4-nitrophenylboronic acid (170 mg) was used instead of 2,4-difluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 334.2

[0439] Reference Example 40. Preparation of 2-chloro-4-(2-fluoro-4-(difluoromethyl)phenyl)-6,7-dimethylpteridine

[0440] The title compound (26 mg, yield: 11.2%) was prepared in the same manner as in Reference Example 1, except that 2-fluoro-4-(difluoromethyl)phenylboronic acid (200 mg) was used instead of 2,4-difluorophenylboronic acid. LC / MS (ESI+) m / z [M+H]+: 339.1

[0441] Reference Example 41. Preparation of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0442] The title compound (46 mg, yield: 61.8%) was prepared in the same manner as in Reference Example 1, except that 2,4-dichloro-6,7-dimethylpyrido[2,3-d]pyrimidine (200 mg) was used instead of 2,4-dichloro-6,7-dimethylpteridine. LC / MS (ESI+) m / z [M+H]+: 306.1

[0443] Reference Example 42. Preparation of 2-chloro-4-(4-chloro-2-fluorophenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0444] The title compound (33 mg, yield: 46.8%)) was prepared in the same manner as in Reference Example 3, except that 2,4-dichloro-6,7-dimethylpyrido[2,3-d]pyrimidine (50 mg) was used instead of 2,4-dichloro-6,7-dimethylpteridine. LC / MS (ESI+) m / z [M+H]+: 322.2

[0445] Reference Example 43. Preparation of 4-(2-chloro-6,7-dimethylpyrido[2,3-d]pyrimidin-4-yl)-3-fluorobenzonitrile

[0446] The title compound (101 mg, yield: 14.6%) was prepared in the same manner as in Reference Example 18, except that 2,4-dichloro-6,7-dimethylpyrido[2,3-d]pyrimidine (500 mg) was used instead of 2,4-dichloro-6,7-dimethylpteridine. LC / MS (ESI+) m / z [M+H]+: 313.1

[0447] Reference Example 44. Preparation of 8-chloro-2,3-dimethyl-6-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazine

[0448] 6,8-dichloro-2,3-dimethylpyrido[2,3-b]pyrazine (600 mg) and 2-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)pyridine (900 mg) were dissolved in dioxane (10.0 mL) and purified water (3.0 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (96.2 mg) and cesium carbonate (1.7 g) thereto, the mixture was stirred for 1 hour at 60°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 1) to prepare the title compound (457 mg, yield: 49.5%). LC / MS (ESI+) m / z [M+H]+: 351.1

[0449] Reference Example 45. Preparation of 8-chloro-6-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-2,3-dimethylpyrido[2,3-b]pyrazine

[0450] The title compound (591 mg, yield: 58.2%) was prepared in the same manner as in Reference Example 44, except that 1-[3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-methyl-piperazine (1.0 g) was used instead of 2-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)pyridine. LC / MS (ESI+) m / z [M+H]+: 386.1

[0451] Example 1. Preparation of 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0452] 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine (45 mg) prepared in Reference Example 1 and 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (62.5 mg) were dissolved in dioxane (2.0 mL) and purified water (0.5 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (5.7 mg) and cesium carbonate (95.6 mg) thereto, the mixture was stirred for 4 hours at 60°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 1) to prepare the title compound (8.5 mg, yield: 13.5%).

[0453] 1H NMR (400 MHz, CDCl3) δ 8.86 (s, 1H), 8.61 (d, 1H), 7.91-7.86 (m, 2H), 7.79 (s, 1H), 7.65 (d, 1H), 7.52 (t, 1H), 7.13 (t, 1H), 7.03 (t, 1H), 3.98 (s, 3H), 2.87 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=429.1 [M+H]+.

[0454] Example 2. Preparation of 4-(2,4-difluoro-5-methylphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0455] The title compound (3.0 mg, yield: 4.6%) was prepared in the same manner as in Example 1, except that 2-chloro-4-(2,4-difluoro-5-methylphenyl)-6,7-dimethylpteridine (45 mg) prepared in Reference Example 2 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0456] 1H NMR (400 MHz, CDCl3) δ 8.86 (s, 1H), 8.62 (d, 1H), 7.90 (s, 1H), 7.80 (s, 1H), 7.69-7.64 (m, 2H), 7.53 (t, 1H), 6.98 (t, 1H), 3.98 (s, 3H), 2.88 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=443.1 [M+H]+.

[0457] Example 3. Preparation of (4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0458] The title compound was prepared in a yield of 11.8% in the same manner as in Example 1, except that 2-chloro-4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridine (20 mg) prepared in Reference Example 3 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0459] 1H NMR (400 MHz, MeOD) δ 8.83 (s, 1H), 8.50 (d, 1H), 7.95 (s, 1H), 7.87 (s, 1H), 7.71-7.69 (m, 1H), 7.68 (d, 1H), 7.64-7.60 (m, 1H), 7.47-7.45 (m, 2H), 3.98 (s, 3H), 2.84 (s, 3H), 2.76 (s, 3H). LC / MS (ESI+) m / z=445.1 [M+H]+.

[0460] Example 4. Preparation of (4-(5-chloro-2,4-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0461] The title compound was prepared in a yield of 11.2% in the same manner as in Example 1, except that 2-chloro-4-(5-chloro-2,4-difluorophenyl)-6,7-dimethylpteridine (25 mg) prepared in Reference Example 4 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0462] 1H NMR (400 MHz, MeOD) δ 8.80 (s, 1H), 8.49 (d, 1H), 8.07 (s, 1H), 8.04 (d, 1H), 7.95 (s, 1H), 7.76 (d, 1H), 7.55 (d, 1H), 7.42 (d, 1H), 3.99 (s, 3H), 2.86 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=463.1 [M+H]+.

[0463] Example 5. Preparation of (6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(2,4,5-trifluorophenyl)pteridine

[0464] The title compound was prepared in a yield of 3.8% in the same manner as in Example 1, except that 2-chloro-6,7-dimethyl-4-(2,4,5-trifluorophenyl)pteridine (20 mg) prepared in Reference Example 5 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0465] 1H NMR (400 MHz, MeOD) δ 8.84 (s, 1H), 8.51 (d, 1H), 8.11 (s, 1H), 8.96 (s, 1H), 7.87-7.85 (m, 1H), 7.77 (d, 1H), 7.58-7.56 (m, 1H), 7.48-7.42 (m, 1H), 3.99 (s, 3H), 2.89 (s, 3H), 2.77 (s, 3H). LC / MS (ESI+) m / z=447.1 [M+H]+.

[0466] Example 6. Preparation of 6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(2,3,4-trifluorophenyl)pteridine

[0467] The title compound was prepared in a yield of 3.6% in the same manner as in Example 1, except that 2-chloro-6,7-dimethyl-4-(2,3,4-trifluorophenyl)pteridine (20 mg) prepared in Reference Example 6 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0468] 1H NMR (400 MHz, MeOD) δ 8.86 (s, 1H), 8.52 (d, 1H), 8.12 (s, 1H), 7.97 (s, 1H), 7.92-7.88 (m, 1H), 7.86 (d, 1H), 7.60-7.58 (m, 1H), 7.49-7.45 (m, 1H), 3.99 (s, 3H), 2.89 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=447.1 [M+H]+.

[0469] Example 7. Preparation of 4-(2,4-difluoro-3-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0470] The title compound was prepared in a yield of 3.3% in the same manner as in Example 1, except that 2-chloro-4-(2,4-difluoro-3-(trifluoromethyl)phenyl)-6,7-dimethylpteridine (20 mg) prepared in Reference Example 7 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0471] 1H NMR (400 MHz, MeOD) δ 8.86 (s, 1H), 8.52 (d, 1H), 8.12 (s, 1H), 7.97 (s, 1H), 7.89-7.79 (m, 1H), 7.76 (d, 1H), 7.60-7.56 (m, 1H), 7.46-7.45 (m, 1H), 3.99 (s, 3H), 2.89 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=497.1 [M+H]+.

[0472] Example 8. Preparation of 4-(3-chloro-2,4-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0473] The title compound was prepared in a yield of 3.5% in the same manner as in Example 1, except that 2-chloro-4-(3-chloro-2,4-difluorophenyl)-6,7-dimethylpteridine (20 mg) prepared in Reference Example 8 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0474] 1H NMR (400 MHz, MeOD) δ 8.87 (s, 1H), 8.52 (d, 1H), 8.07 (s, 1H), 7.96 (s, 1H), 7.89-7.80 (m, 1H), 7.75 (d, 1H), 7.58-7.56 (m, 1H), 7.46-7.45 (m, 1H), 3.99 (s, 3H), 2.89 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=463.1 [M+H]+.

[0475] Example 9. Preparation of 4-(2,4-difluoro-3-methylphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0476] The title compound was prepared in a yield of 3.6% in the same manner as in Example 1, except that 2-chloro-4-(2,4-difluoro-3-methylphenyl)-6,7-dimethylpteridine (20 mg) prepared in Reference Example 9 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0477] 1H NMR (400 MHz, MeOD) δ 8.85 (s, 1H), 8.51 (d, 1H), 8.11 (s, 1H), 7.96 (s, 1H), 7.78-7.74 (m, 2H), 7.59-7.55 (m, 1H), 7.22-7.17 (m, 1H), 3.99 (s, 3H), 2.89 (s, 3H), 2.77 (s, 3H). LC / MS (ESI+) m / z=443.1 [M+H]+.

[0478] Example 10. Preparation of 4-(2,4-difluoro-3-methoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0479] The title compound was prepared in a yield of 7.1% in the same manner as in Example 1, except that 2-chloro-4-(2,4-difluoro-3-methoxyphenyl)-6,7-dimethylpteridine (20 mg) prepared in Reference Example 10 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0480] 1H NMR (400 MHz, MeOD) δ 8.80 (s, 1H), 8.48 (d, 1H), 8.09 (s, 1H), 7.94 (s, 1H), 7.74 (d, 1H), 7.59-7.57 (m, 2H), 7.27-7.24 (m, 1H), 4.08 (s, 3H), 3.98 (s, 3H), 2.86 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=459.1 [M+H]+.

[0481] Example 11. Preparation of 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0482] The title compound was prepared in a yield of 12.3% in the same manner as in Example 1, except that 2-chloro-4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine (20 mg) prepared in Reference Example 11 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0483] 1H NMR (400 MHz, MeOD) δ 8.86 (s, 1H), 8.52 (d, 1H), 8.11-8.06 (m, 2H), 7.96 (s, 1H), 7.79-7.72 (m, 3H), 7.59-7.55 (m, 1H), 3.98 (s, 3H), 2.89 (s, 3H), 2.76 (s, 3H). LC / MS (ESI+) m / z=479.1 [M+H]+.

[0484] Example 12. Preparation of 4-(2-fluoro-4-(methylthio)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0485] The title compound was prepared in a yield of 13.7% in the same manner as in Example 1, except that 2-chloro-4-(2-fluoro-4-(methylthio)phenyl)-6,7-dimethylpteridine (20 mg) prepared in Reference Example 12 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0486] 1H NMR (400 MHz, MeOD) δ 8.78 (s, 1H), 8.51 (d, 1H), 7.96 (s, 1H), 7.88 (s, 1H), 7.71-7.69 (m, 1H), 7.67 (d, 1H), 7.64-7.60 (m, 1H), 7.47-7.45 (m, 2H), 3.98 (s, 3H), 2.84 (s, 3H), 2.76 (s, 3H), 2.62 (s, 3H). LC / MS (ESI+) m / z=457.1 [M+H]+.

[0487] Example 13. Preparation of 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0488] The title compound was prepared in a yield of 12.2% in the same manner as in Example 1, except that 2-chloro-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine (20 mg) prepared in Reference Example 13 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0489] 1H NMR (400 MHz, MeOD) δ 8.75 (s, 1H), 8.44 (d, 1H), 8.04 (s, 1H), 7.91 (s, 1H), 7.77-7.71 (m, 2H), 7.52-7.48 (m, 1H), 7.22 (d, 1H), 7.15 (d, 1H), 3.95 (s, 3H), 2.82 (s, 3H), 2.70 (s, 3H), 2.52 (s, 3H). LC / MS (ESI+) m / z=425.2 [M+H]+.

[0490] Example 14. Preparation of 4-(2-fluoro-4-methoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0491] The title compound was prepared in a yield of 8.3% in the same manner as in Example 1, except that 2-chloro-4-(2-fluoro-4-methoxyphenyl)-6,7-dimethylpteridine (20 mg) prepared in Reference Example 14 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0492] 1H NMR (400 MHz, MeOD) δ 8.87 (s, 1H), 8.47 (d, 1H), 8.08 (s, 1H), 7.92-7.74 (m, 3H), 7.55-7.51 (m, 1H), 7.02 (d, 1H), 6.96 (d, 1H), 4.08 (s, 3H), 3.95 (s, 3H), 2.85 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=411.2 [M+H]+.

[0493] Example 15. Preparation of N-cyclopropyl-4-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluoro-N-methylbenzenesulfonamide

[0494] The title compound was prepared in a yield of 9.1% in the same manner as in Example 1, except that 4-(2-chloro-6,7-dimethylpteridin-4-yl)-N-cyclopropyl-3-fluoro-N-methylbenzenesulfonamide (20 mg) prepared in Reference Example 15 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0495] 1H NMR (400 MHz, MeOD) δ 8.87 (s, 1H), 8.47 (d, 1H), 8.16-8.07 (m, 3H), 7.96-7.94 (m, 1H), 7.84-7.77 (m, 2H), 7.48-7.44 (m, 1H), 3.98 (s, 3H), 2.91 (s, 3H), 2.89 (s, 3H), 2.77 (s, 3H), 2.05-2.03 (m, 1H), 0.95-0.83 (m, 4H). LC / MS (ESI+) m / z=544.2 [M+H]+.

[0496] Example 16. Preparation of 4-(2-fluoro-4-isopropoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0497] The title compound was prepared in a yield of 18.7% in the same manner as in Example 1, except that 2-chloro-4-(2-fluoro-4-isopropoxyphenyl)-6,7-dimethylpteridine (20 mg) prepared in Reference Example 16 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0498] 1H NMR (400 MHz, MeOD) δ 8.84 (s, 1H), 8.48 (d, 1H), 8.09 (s, 1H), 7.93 (s, 1H), 7.78-7.75 (m, 1H), 7.59-7.56 (m, 2H), 7.07-7.05 (m, 1H), 6.94-6.89 (m, 1H), 4.75-4.70 (m, 1H), 3.98 (s, 3H), 2.89 (s, 3H), 2.74 (s, 3H), 1.24 (d, 3H), 1.13 (d, 3H). LC / MS (ESI+) m / z=469.2 [M+H]+.

[0499] Example 17. Preparation of 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0500] The title compound (9.8 mg, yield: 2.5%) was prepared in the same manner as in Example 1, except that 1-methyl-4-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (67.5 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0501] 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 8.45 (s, 1H), 7.89-7.88 (m, 2H), 7.77 (s, 1H), 7.47 (s, 1H), 7.13 (t, 1H), 7.03 (t, 1H), 3.97 (s, 3H), 2.87 (s, 3H), 2.74 (s, 3H), 2.49 (s, 3H). LC / MS (ESI+) m / z=443.2 [M+H]+.

[0502] Example 18. Preparation of 4-(2,4-difluoro-5-methylphenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0503] The title compound (6.7 mg, yield: 1.7%) was prepared in the same manner as in Example 2, except that 1-methyl-4-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (67.5 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0504] 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 8.45 (s, 1H), 7.89 (s, 1H), 7.78 (s, 1H), 7.71-7.67 (m, 1H), 7.47 (s, 1H), 6.98 (t, 1H), 3.97 (s, 3H), 2.87 (s, 3H), 2.75 (s, 3H), 2.50 (s, 3H), 2.39 (s, 3H). LC / MS (ESI+) m / z=457.2 [M+H]+.

[0505] Example 19. Preparation of 4-(4-chloro-2,3-difluoro-5-methoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0506] The title compound was prepared in a yield of 12.5% in the same manner as in Example 1, except that 2-chloro-4-(4-chloro-2,3-difluoro-5-methoxyphenyl)-6,7-dimethylpteridine (20 mg) prepared in Reference Example 17 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0507] 1H NMR (400 MHz, MeOD) δ 8.85 (s, 1H), 8.52 (d, 1H), 8.11 (s, 1H), 7.96 (s, 1H), 7.83-7.79 (m, 1H), 7.59-7.55 (m, 1H), 7.40-7.38 (m, 1H), 4.01 (s, 3H), 3.99 (s, 3H), 2.89 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=492.9 [M+H]+.

[0508] Example 20. Preparation of 4-(5-chloro-2,4-difluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0509] The title compound was prepared in a yield of 8.9% in the same manner as in Example 4, except that 1-methyl-4-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (67.5 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0510] 1H NMR (400 MHz, MeOD) δ 8.67 (s, 1H), 8.38 (s, 1H), 8.06 (s, 1H), 7.92-7.88 (m, 2H), 7.59 (s, 1H), 7.50-7.46 (m, 2H), 3.98 (s, 3H), 2.86 (s, 3H), 2.74 (s, 3H), 2.49 (s, 3H). LC / MS (ESI+) m / z=477.1 [M+H]+.

[0511] Example 21. Preparation of 4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0512] The title compound was prepared in a yield of 7.0% in the same manner as in Example 3, except that 1-methyl-4-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (67.5 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0513] 1H NMR (400 MHz, MeOD) δ 8.61 (s, 1H), 8.39 (s, 1H), 8.03 (s, 1H), 7.93-7.87 (m, 1H), 7.73-7.70 (m, 2H), 7.50-7.40 (m, 1H), 3.98 (s, 3H), 2.88 (s, 3H), 2.76 (s, 3H), 2.52 (s, 3H). LC / MS (ESI+) m / z=459.1 [M+H]+.

[0514] Example 22. Preparation of 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0515] The title compound was prepared in a yield of 13.5% in the same manner as in Example 11, except that 1-methyl-4-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (67.5 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0516] 1H NMR (400 MHz, MeOD) δ 8.54 (s, 1H), 8.28 (s, 1H), 8.08 (s, 1H), 7.87-7.74 (m, 2H), 7.67 (s, 1H), 7.65-7.51 (m, 2H), 3.96 (s, 3H), 2.82 (s, 3H), 2.69 (s, 3H), 2.45 (s, 3H). LC / MS (ESI+) m / z=493.1 [M+H]+.

[0517] Example 23. Preparation of 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0518] The title compound was prepared in a yield of 12.9% in the same manner as in Example 13, except that 1-methyl-4-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (67.5 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0519] 1H NMR (400 MHz, MeOD) δ 8.58 (s, 1H), 8.30 (s, 1H), 8.05 (s, 1H), 7.83-7.75 (m, 2H), 7.67 (s, 1H), 7.63-7.51 (m, 2H), 3.97 (s, 3H), 2.79 (s, 3H), 2.70 (s, 3H), 2.50 (s, 3H), 2.44 (s, 3H). LC / MS (ESI+) m / z=493.5 [M+H]+.

[0520] Example 24. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0521] The title compound was prepared in a yield of 3.5% in the same manner as in Example 3, except that 3-(1-ethylpyrazol-4-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0522] 1H NMR (400 MHz, MeOD) δ 8.86 (s, 1H), 8.53 (d, 1H), 8.16 (s, 1H), 7.97 (s, 1H), 7.89-7.78 (m, 2H), 7.59-7.56 (m, 1H), 7.51-7.47 (m, 2H), 4.27 (q, 2H), 2.88 (s, 3H), 2.77 (s, 3H), 1.53 (t, 3H). LC / MS (ESI+) m / z=459.1 [M+H]+.

[0523] Example 25. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0524] The title compound was prepared in a yield of 12.6% in the same manner as in Example 3, except that 3-(1-isopropylpyrazol-4-yl)phenylboronic acid (52 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0525] 1H NMR (400 MHz, MeOD) δ 8.79 (s, 1H), 8.45 (d, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.89-7.87 (m, 1H), 7.76-7.74 (m, 1H), 7.54-7.44 (m, 3H), 4.64-4.58 (m, 1H), 2.88 (s, 3H), 2.77 (s, 3H), 1.58 (d, 3H), 1.54 (d, 3H). LC / MS (ESI+) m / z=473.1 [M+H]+.

[0526] Example 26. Preparation of 4-(2-fluoro-4-methylphenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0527] The title compound was prepared in a yield of 10.0% in the same manner as in Example 13, except that 3-(1-isopropylpyrazol-4-yl)phenylboronic acid (52 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0528] 1H NMR (400 MHz, MeOD) δ 8.82 (s, 1H), 8.48 (d, 1H), 8.17 (s, 1H), 7.96 (s, 1H), 7.78-7.76 (m, 2H), 7.55-7.52 (m, 1H), 7.26-7.24 (m, 1H), 7.16 (d, 1H), 4.62-4.59 (m, 1H), 2.85 (s, 3H), 2.73 (s, 3H), 1.57 (d, 3H), 1.54 (d, 3H). LC / MS (ESI+) m / z=453.2 [M+H]+.

[0529] Example 27. Preparation of 4-(2-fluoro-4-methylphenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0530] The title compound was prepared in a yield of 9.7% in the same manner as in Example 13, except that 3-(1-isobutyl-1H-pyrazol-4-yl)phenylboronic acid (56 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0531] 1H NMR (400 MHz, MeOD) δ 8.83 (s, 1H), 8.49 (d, 1H), 8.12 (s, 1H), 7.97 (s, 1H), 7.77-7.74 (m, 2H), 7.56-7.52 (m, 1H), 7.25 (d, 1H), 7.17 (d, 1H), 4.02 (d, 2H), 2.86 (s, 3H), 2.74 (s, 3H), 2.53 (s, 3H), 2.24-2.18 (m, 1H), 0.99 (s, 3H), 0.97 (s, 3H). LC / MS (ESI+) m / z=467.2 [M+H]+.

[0532] Example 28. Preparation of 2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine

[0533] The title compound was prepared in a yield of 10.1% in the same manner as in Example 11, except that 3-(1-ethylpyrazol-4-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0534] 1H NMR (400 MHz, MeOD) δ 8.82 (s, 1H), 8.49 (d, 1H), 8.14 (s, 1H), 8.08 (t, 1H), 7.96 (s, 1H), 7.78-7.71 (m, 3H), 7.56-7.52 (m, 1H), 4.26 (q, 2H), 2.87 (s, 3H), 2.74 (s, 3H), 1.56 (t, 3H). LC / MS (ESI+) m / z=493.1 [M+H]+.

[0535] Example 29. Preparation of 4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0536] The title compound was prepared in a yield of 26.4% in the same manner as in Example 11, except that 3-(1-isopropylpyrazol-4-yl)phenylboronic acid (52 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0537] 1H NMR (400 MHz, MeOD) δ 8.73 (s, 1H), 8.41 (d, 1H), 8.14 (s, 1H), 8.07 (t, 1H), 7.93 (s, 1H), 7.74-7.71 (m, 3H), 7.51-7.49 (m, 1H), 4.61-4.56 (m, 1H), 2.81 (s, 3H), 2.68 (s, 3H), 1.58 (d, 3H), 1.53 (d, 3H). LC / MS (ESI+) m / z=507.2 [M+H]+.

[0538] Example 30. Preparation of 4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0539] The title compound was prepared in a yield of 20.6% in the same manner as in Example 11, except that 3-(1-isobutyl-1H-pyrazol-4-yl)phenylboronic acid (56 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0540] 1H NMR (400 MHz, MeOD) δ 8.78 (s, 1H), 8.45 (d, 1H), 8.10-8.06 (m, 2H), 7.95 (s, 1H), 7.84-7.72 (m, 3H), 7.53-7.49 (m, 1H), 4.02-3.96 (m, 2H), 2.84 (s, 3H), 2.71 (s, 3H), 2.27-2.21 (m, 1H), 0.98 (s, 3H), 0.94 (s, 3H). LC / MS (ESI+) m / z=521.2 [M+H]+.

[0541] Example 31. Preparation of 4-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0542] The title compound (16.0 mg, yield: 2.8%) was prepared in the same manner as in Example 1, except that 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile (95 mg) prepared in Reference Example 18 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0543] 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 8.58 (d, 1H), 7.95 (t, 1H), 7.77 (s, 1H), 7.70 (s, 1H), 7.68-7.59 (m, 2H), 7.56-7.50 (m, 2H), 3.97 (s, 3H), 2.88 (s, 3H), 2.73 (s, 3H). LC / MS (ESI+) m / z=436.1 [M+H]+.

[0544] Example 32. Preparation of 4-(2,5-difluoropyridin-4-yl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0545] The title compound (2.9 mg, yield: 0.5%) was prepared in the same manner as in Example 1, except that 2-chloro-4-(2,5-difluoropyridin-4-yl)-6,7-dimethylpteridine (95 mg) prepared in Reference Example 19 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0546] 1H NMR (400 MHz, CDCl3) δ 8.84 (s, 1H), 8.60 (d, 1H), 8.29 (s, 1H), 8.09 (s, 1H), 7.90 (s, 1H), 7.80 (s, 1H), 7.67 (d, 1H), 7.54 (t, 1H), 3.99 (s, 3H), 2.90 (s, 3H), 2.77 (s, 3H). LC / MS (ESI+) m / z=430.2 [M+H]+.

[0547] Example 33. Preparation of 6-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine

[0548] The title compound (3.2 mg, yield: 0.5%) was prepared in the same manner as in Example 1, except that 6-(2-chloro-6,7-dimethylpteridin-4-yl)-7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine (98 mg) prepared in Reference Example 20 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0549] 1H NMR (400 MHz, CDCl3) δ 8.88 (s, 1H), 8.65 (d, 1H), 7.92 (s, 1H), 7.82 (s, 1H), 7.66 (d, 1H), 7.54 (t, 1H), 7.17 (d, 1H), 6.75 (d, 1H), 4.39 (d, 2H), 4.01 (s, 3H), 3.51 (s, 2H), 2.89 (s, 3H), 2.79 (s, 3H). LC / MS (ESI+) m / z=468.2 [M+H]+.

[0550] Example 34. Preparation of 6-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-7-fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one

[0551] The title compound (3.1 mg, yield: 0.5%) was prepared in the same manner as in Example 1, except that 6-(2-chloro-6,7-dimethylpteridin-4-yl)-7-fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one (98 mg) prepared in Reference Example 21 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0552] 1H NMR (400 MHz, CDCl3) δ 8.92 (s, 1H), 8.86 (s, 1H), 8.60 (d, 1H), 7.90 (s, 1H), 7.81 (s, 1H), 7.66 (d, 1H), 7.52 (t, 1H), 7.45 (d, 1H), 6.93 (d, 1H), 4.74 (s, 2H), 3.71 (s, 4H), 2.89 (s, 3H), 2.77 (s, 3H). LC / MS (ESI+) m / z=482.1 [M+H]+.

[0553] Example 35. Preparation of 6-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-5-fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one

[0554] The title compound (8.5 mg, yield: 1.4%) was prepared in the same manner as in Example 1, except that 6-(2-chloro-6,7-dimethylpteridin-4-yl)-5-fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one (98 mg) prepared in Reference Example 22 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0555] 1H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.61 (d, 1H), 7.94 (s, 1H), 7.89 (s, 1H), 7.78 (s, 1H), 7.67-7.64 (m, 1H), 7.56-745 (m, 2H), 7.03 (d, 1H), 4.77 (s, 2H), 3.98 (s, 3H), 2.88 (s, 3H), 2.76 (s, 3H). LC / MS (ESI+) m / z=482.2 [M+H]+.

[0556] Example 36. Preparation of 4-(8-fluoroquinolin-7-yl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0557] The title compound (9.5 mg, yield: 22.7%) was prepared in the same manner as in Example 17, except that 2-chloro-4-(8-fluoroquinolin-7-yl)-6,7-dimethylpteridine (98 mg) prepared in Reference Example 23 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0558] 1H NMR (400 MHz, CDCl3) δ 9.07 (s, 1H), 8.66 (s, 1H), 8.47 (s, 1H), 8.31 (d, 1H), 7.98 (t, 1H), 7.86-7.77 (m, 3H), 7.600-7.599 (m, 1H), 7.46 (s, 1H), 3.94 (s, 3H), 2.87 (s, 3H), 2.71 (s, 3H), 2.47 (s, 3H). LC / MS (ESI+) m / z=476.2 [M+H]+.

[0559] Example 37. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0560] The title compound was prepared in a yield of 6.9% in the same manner as in Example 3, except that 3-(1-cyclopropylpyrazol-4-yl)phenylboronic acid (52 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0561] 1H NMR (400 MHz, MeOD) δ 8.72 (s, 1H), 8.43 (d, 1H), 8.13 (s, 1H), 7.90-7.83 (m, 2H), 7.71-7.69 (m, 1H), 7.55-7.43 (m, 3H), 3.73-3.71 (m, 1H), 2.86 (s, 3H), 2.70 (s, 3H), 1.18-1.08 (m, 4H). LC / MS (ESI+) m / z=471.1 [M+H]+.

[0562] Example 38. Preparation of 4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine

[0563] The title compound was prepared in a yield of 7.3% in the same manner as in Example 3, except that (5-(1-methyl-1H-pyrazol-4-yl)pyridine-3-boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0564] 1H NMR (400 MHz, MeOD) δ 9.34 (s, 1H), 8.82 (s, 1H), 8.75 (d, 1H), 8.24-7.88 (m, 3H), 7.45-7.40 (m, 2H), 3.95 (s, 3H), 2.82 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=446.1 [M+H]+.

[0565] Example 39. Preparation of 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine

[0566] The title compound was prepared in a yield of 3.8% in the same manner as in Example 13, except that (5-(1-methyl-1H-pyrazol-4-yl)pyridine-3-boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0567] 1H NMR (400 MHz, MeOD) δ 9.60 (s, 1H), 9.16 (s, 1H), 8.95 (s, 1H), 8.25 (s, 1H), 8.03 (s, 1H), 7.77-7.73 (m, 1H), 7.29-7.18 (m, 2H), 3.99 (s, 3H), 2.90 (s, 3H), 2.79 (s, 3H), 2.50 (s, 3H). LC / MS (ESI+) m / z=426.1 [M+H]+.

[0568] Example 40. Preparation of 2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine

[0569] The title compound was prepared in a yield of 6.4% in the same manner as in Example 11, except that 3-(1-cyclopropylpyrazol-4-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0570] 1H NMR (400 MHz, MeOD) δ 8.78 (s, 1H), 8.46 (d, 1H), 8.16 (s, 1H), 8.06 (t, 1H), 7.91 (s, 1H), 7.76-7.70 (m, 3H), 7.54-7.50 (m, 1H), 3.73-3.71 (m, 1H), 2.85 (s, 3H), 2.72 (s, 3H), 1.40-1.30 (m, 2H), 1.13-1.10 (m, 2H). LC / MS (ESI+) m / z=505.1 [M+H]+.

[0571] Example 41. Preparation of 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine

[0572] The title compound was prepared in a yield of 6.7% in the same manner as in Example 11, except that (5-(1-methyl-1H-pyrazol-4-yl)pyridine-3-boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0573] 1H NMR (400 MHz, MeOD) δ 9.45 (s, 1H), 8.98 (s, 1H), 8.84 (s, 1H), 8.17 (s, 1H), 8.08-7.99 (m, 2H), 7.75-7.69 (m, 2H), 3.96 (s, 3H), 2.85 (s, 3H), 2.73 (s, 3H). LC / MS (ESI+) m / z=480.1 [M+H]+.

[0574] Example 42. Preparation of (3-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-2,6-difluorophenyl)methanol

[0575] The title compound (4.2 mg, yield: 1.1%) was prepared in the same manner as in Example 1, except that (3-(2-chloro-6,7-dimethylpteridin-4-yl)-2,6-difluorophenyl)methanol (50 mg) prepared in Reference Example 24 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0576] 1H NMR (400 MHz, CDCl3) δ 8.84 (s, 1H), 8.60 (d, 1H), 7.90 (s, 1H), 7.83-7.79 (m, 2H), 7.68-7.64 (m, 1H), 7.50 (t, 1H), 7.16 (t, 1H), 4.93 (s, 2H), 3.98 (s, 3H), 2.88 (s, 3H), 2.74 (s, 3H). LC / MS (ESI+) m / z=459.1 [M+H]+.

[0577] Example 43. Preparation of 6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(2,3,4-trifluoro-5-methylphenyl)pteridine

[0578] The title compound (5.9 mg, yield: 1.5%) was prepared in the same manner as in Example 1, except that 2-chloro-6,7-dimethyl-4-(2,3,4-trifluoro-5-methylphenyl)pteridine (34 mg) prepared in Reference Example 25 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0579] 1H NMR (400 MHz, CDCl3) δ 8.84 (s, 1H), 8.60 (d, 2H), 7.90 (s, 1H), 7.79 (s, 1H), 7.67-7.65 (m, 1H), 7.55-7.53 (m, 1H), 7.46-7.44 (m, 1H), 3.98 (s, 3H), 2.88 (s, 3H), 2.76 (s, 3H), 2.42 (s, 3H). LC / MS (ESI+) m / z=461.1 [M+H]+.

[0580] Example 44. Preparation of 4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine

[0581] The title compound was prepared in a yield of 7.3% in the same manner as in Example 3, except that (3-(pyridin-4-yl)phenyl)boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0582] 1H NMR (400 MHz, MeOD) δ 9.08 (s, 1H), 8.81 (d, 1H), 8.68-8.65 (m, 2H), 8.02-7.89 (m, 3H), 7.78-7.69 (m, 2H), 7.50-7.47 (m, 2H), 2.90 (s, 3H), 2.73 (s, 3H). LC / MS (ESI+) m / z=442.1 [M+H]+.

[0583] Example 45. Preparation of 2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine

[0584] The title compound was prepared in a yield of 7.2% in the same manner as in Example 13, except that 3-(1-cyclopropylpyrazol-4-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0585] 1H NMR (400 MHz, MeOD) δ 8.86 (s, 1H), 8.52 (d, 1H), 8.19 (s, 1H), 7.92 (s, 1H), 7.78-7.74 (m, 2H), 7.58-7.55 (m, 1H), 7.27 (d, 1H), 7.18 (d, 1H), 3.76-3.74 (m, 1H), 2.88 (s, 3H), 2.77 (s, 3H), 2.54 (s, 3H), 1.36-1.31 (m, 2H), 1.18-1.11 (m, 2H). LC / MS (ESI+) m / z=451.1 [M+H]+.

[0586] Example 46. Preparation of 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine

[0587] The title compound was prepared in a yield of 7.3% in the same manner as in Example 11, except that (3-(pyridin-4-yl)phenyl)boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0588] 1H NMR (400 MHz, MeOD) δ 9.09 (s, 1H), 8.80 (d, 1H), 8.68-8.66 (m, 2H), 8.09-8.03 (m, 2H), 7.89-7.87 (m, 2H), 7.79-7.68 (m, 3H), 2.91 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=476.1 [M+H]+.

[0589] Example 47. Preparation of 4-(2-fluoro-3-methoxy-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0590] The title compound (14.1 mg, yield: 3.2%) was prepared in the same manner as in Example 1, except that 2-chloro-4-(2-fluoro-3-methoxy-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine (50 mg) prepared in Reference Example 26 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0591] 1H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.60 (d, 1H), 7.89 (s, 1H), 7.79 (s, 1H), 7.66 (d, 1H), 7.58 (s, 1H), 7.52 (t, 3H), 4.09 (s, 3H), 3.98 (s, 3H), 2.89 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=509.1 [M+H]+.

[0592] Example 48. Preparation of 4-(2,3-difluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0593] The title compound (10.0 mg, yield: 2.3%) was prepared in the same manner as in Example 1, except that 2-chloro-4-(2,3-difluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine (55 mg) prepared in Reference Example 27 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0594] 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 8.58 (d, 1H), 7.88 (s, 1H), 7.78 (s, 1H), 7.70-7.60 (m, 3H), 7.52 (t, 1H), 3.97 (s, 1H), 2.89 (s, 1H), 2.76 (s, 1H). LC / MS (ESI+) m / z=497.1 [M+H]+.

[0595] Example 49. Preparation of 4-(5-chloro-2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0596] The title compound (9.3 mg, yield: 2.1%) was prepared in the same manner as in Example 1, except that 2-chloro-4-(5-chloro-2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine (53 mg) prepared in Reference Example 28 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0597] 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 8.59 (d, 1H), 7.97 (d, 1H), 7.89 (s, 1H), 7.79 (s, 1H), 7.67- 7.62 (m, 2H), 7.53 (t, 1H), 3.97 (s, 3H), 2.88 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=513.1 [M+H]+.

[0598] Example 50. Preparation of 5-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-2-(trifluoromethyl)thiazole

[0599] The title compound (3.7 mg, yield: 0.9%) was prepared in the same manner as in Example 1, except that 5-(2-chloro-6,7-dimethylpteridin-4-yl)-2-(trifluoromethyl)thiazole (45 mg) prepared in Reference Example 29 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0600] 1H NMR (400 MHz, CDCl3) δ 9.36 (s, 1H), 8.92 (s, 1H), 8.69 (d, 1H), 7.93 (s, 1H), 7.82 (s, 1H), 7.68 (d, 1H), 7.56 (t, 1H), 4.00 (s, 3H), 2.89 (d, 6H). LC / MS (ESI+) m / z=468.1 [M+H]+.

[0601] Example 51. Preparation of 6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pteridine

[0602] The title compound (11.5 mg, yield: 2.8%) was prepared in the same manner as in Example 1, except that 2-chloro-6,7-dimethyl-4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pteridine (43 mg) prepared in Reference Example 30 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0603] 1H NMR (400 MHz, CDCl3) δ 8.91 (s, 1H), 8.87 (s, 2H), 8.64 (d, 1H), 7.93 (s, 1H), 7.82 (s, 1H), 7.66 (d, 1H), 7.55 (t, 1H), 4.55-4.52 (m, 1H), 4.21 (d, 2H), 3.99 (s, 1H), 3.67-3.61 (m, 2H), 2.87 (s, 6H), 2.27-2.23 (m, 4H). LC / MS (ESI+) m / z=467.2 [M+H]+.

[0604] Example 52. Preparation of 3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0605] The title compound (3.2 mg, yield: 10.8%) was prepared in the same manner as in Example 31, except that 3-(1-isopropylpyrazol-4-yl)phenylboronic acid (52 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0606] 1H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.58 (d, 1H), 7.96 (t, 1H), 7.88 (d, 2H), 7.69 (t, 2H), 7.59 (d, 1H), 7.52 (t, 1H), 7.558-7.550 (m, 1H), 2.89 (s, 3H), 2.74 (s, 3H), 1.58 (d, 6H). LC / MS (ESI+) m / z=464.2 [M+H]+.

[0607] Example 53. Preparation of 4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0608] The title compound (2.4 mg, yield: 8.4%) was prepared in the same manner as in Example 31, except that 1-methyl-4-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (55 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0609] 1H NMR (400 MHz, CDCl3) δ 8.64 (s, 1H), 8.44 (s, 1H), 7.97 (t, 1H), 7.88 (s, 1H), 7.77 (s, 1H), 7.71 (d, 1H), 7.59 (d, 1H), 7.49 (s, 1H), 3.98 (s, 3H), 2.89 (s, 3H), 2.75 (s, 3H), 2.49 (s, 3H). LC / MS (ESI+) m / z=450.1 [M+H]+.

[0610] Example 54. Preparation of 4-(6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0611] The title compound (6.8 mg, yield: 24.7%) was prepared in the same manner as in Example 31, except that (3-(pyridin-3-yl)phenyl)boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0612] 1H NMR (400 MHz, CDCl3) δ 9.00 (s, 2H), 8.80 (d, 1H), 8.66 (s, 1H), 8.04 (d, 1H), 7.98 (t, 1H), 7.79 (d, 1H), 7.732-7.660 (m, 2H), 7.61 (d, 1H) 7.45 (s, 1H), 2.91 (s, 1H), 2.77 (s, 1H). LC / MS (ESI+) m / z=433.1 [M+H]+.

[0613] Example 55. Preparation of 4-(6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0614] The title compound (2.6 mg, yield: 9.4%) was prepared in the same manner as in Example 31, except that (3-(pyridin-4-yl)phenyl)boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0615] 1H NMR (400 MHz, CDCl3) δ 9.04 (s, 1H), 9.82 (d, 1H), 8.71 (s, 2H), 7.97 (t, 1H), 7.83 (d, 1H), 7.726-7.593 (m, 5H), 2.90 (s, 3H), 2.76 (s, 3H). LC / MS (ESI+) m / z=433.1 [M+H]+.

[0616] Example 56. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0617] The title compound was prepared in a yield of 6.5% in the same manner as in Example 3, except that 1-methyl-4-[3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (70 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0618] 1H NMR (400 MHz, MeOD) δ 8.51 (s, 1H), 8.19 (s, 1H), 7.90 (s, 1H), 7.88-7.85 (m, 1H), 7.80 (s, 1H), 7.43-7.23 (m, 3H), 3.99 (s, 3H), 3.96 (s, 3H), 2.91 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=475.1 [M+H]+.

[0619] Example 57. Preparation of 2-([3,4-bipyridin]-5-yl)-4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridine

[0620] The title compound was prepared in a yield of 11.7% in the same manner as in Example 3, except that [3,4'-bipyridin]-5-ylboronic acid (55 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0621] 1H NMR (400 MHz, MeOD) δ 9.99 (s, 1H), 9.25 (s, 1H), 9.05 (s, 1H), 8.77-8.62 (m, 1H), 7.84-7.53 (m, 4H), 7.48-7.29 (m, 2H), 2.91 (s, 3H), 2.79 (s, 3H). LC / MS (ESI+) m / z=443.1 [M+H]+.

[0622] Example 58. Preparation of 4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0623] The title compound was prepared in a yield of 13.5% in the same manner as in Example 3, except that 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (65 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0624] 1H NMR (400 MHz, MeOD) δ 9.02 (s, 1H), 8.75-8.73 (m, 2H), 8.68 (s, 1H), 7.81-7.76 (m, 2H), 7.42-7.33 (m, 2H), 7.29 (s, 1H), 2.88 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=432.1 [M+H]+.

[0625] Example 59. Preparation of 4-(2,3-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0626] The title compound (11.2 mg, yield: 2.4%) was prepared in the same manner as in Example 1, except that 2-chloro-4-(2,3-difluorophenyl)-6,7-dimethylpteridine (75 mg) prepared in Reference Example 31 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0627] 1H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.61 (d, 1H), 7.90 (s, 1H), 7.79 (s, 1H), 7.66-7.61 (m, 2H), 7.54-7.52 (m, 1H), 7.43-7.41 (m, 1H), 7.33-7.31 (m, 1H), 3.98 (s, 3H), 2.88 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=429.1 [M+H]+.

[0628] Example 60. Preparation of 4-(2,5-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0629] The title compound (5.4 mg, yield: 1.2%) was prepared in the same manner as in Example 1, except that 2-chloro-4-(2,5-difluorophenyl)-6,7-dimethylpteridine (80 mg) prepared in Reference Example 32 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0630] 1H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.62 (d, 1H), 7.90 (s, 1H), 7.80 (s, 1H), 7.67-7.65 (m, 1H), 7.58-7.51 (m, 2H), 7.26-7.24 (m, 2H), 3.98 (s, 3H), 2.88 (s, 3H), 2.76 (s, 3H). LC / MS (ESI+) m / z=429.1 [M+H]+.

[0631] Example 61. Preparation of 4-(3,5-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0632] The title compound (1.9 mg, yield: 0.4%) was prepared in the same manner as in Example 1, except that 2-chloro-4-(3,5-difluorophenyl)-6,7-dimethylpteridine (84 mg) prepared in Reference Example 33 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0633] 1H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 8.65-8.59 (m, 2H), 8.50 (s, 1H), 7.91 (s, 1H), 7.80 (s, 1H), 7.67 (d, 1H), 7.55 (t, 1H), 7.40 (q, 1H), 3.99 (s, 3H), 2.89 (s, 3H), 2.84 (s, 3H). LC / MS (ESI+) m / z=429.1 [M+H]+.

[0634] Example 62. Preparation of 4-(2,4-difluorophenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0635] The title compound (4.3 mg, yield: 4.7%) was prepared in the same manner as in Example 1, except that 3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenylboronic acid (65 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0636] 1H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 8.61 (d, 1H), 7.93-7.88 (m, 3H), 7.67 (d, 1H), 7.52 (t, 1H), 7.13 (t, 1H), 7.06 (t, 1H), 4.35 (t, 2H), 3.81 (t, 2H), 3.38 (s, 3H), 2.88 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=473.1 [M+H]+.

[0637] Example 63. Preparation of 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine

[0638] The title compound (5.5 mg, yield: 6.6%) was prepared in the same manner as in Example 1, except that 5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl boronic acid (60 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0639] 1H NMR (400 MHz, CDCl3) δ 9.75 (s, 1H), 9.04 (s, 1H), 8.89 (s, 1H), 7.93 (s, 1H), 7.88 (q, 1H), 7.82 (s, 1H), 7.14 (t, 1H), 7.04 (t, 1H), 4.00 (s, 3H), 2.89 (s, 3H), 2.77 (s, 3H). LC / MS (ESI+) m / z=430.1 [M+H]+.

[0640] Example 64. Preparation of 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine

[0641] The title compound (6.7 mg, yield: 8.1%) was prepared in the same manner as in Example 1, except that 3-(pyridin-4-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0642] 1H NMR (400 MHz, CDCl3) δ 9.06 (s, 1H), 8.85 (d, 1H), 8.72 (d, 1H), 7.90-7.80 (m, 2H), 7.68-7.65 (m, 3H), 7.13 (t, 1H), 7.04 (t, 1H), 2.89 (s, 3H), 2.76 (s, 3H). LC / MS (ESI+) m / z=426.1 [M+H]+.

[0643] Example 65. Preparation of 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0644] The title compound (3.2 mg, yield: 3.9%) was prepared in the same manner as in Example 1, except that 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (55 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0645] 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 8.73 (d, 1H), 8.67 (s, 1H), 7.84 (q, 1H), 7.75 (d, 1H), 7.13 (t, 1H), 7.03 (t, 1H), 2.86 (s, 3H), 2.74 (s, 3H). LC / MS (ESI+) m / z=416.1 [M+H]+.

[0646] Example 66. Preparation of 4-(6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridin-4-yl)-3-fluorobenzonitrile

[0647] The title compound (1.9 mg, yield: 7.1%) was prepared in the same manner as in Example 31, except that 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0648] 1H NMR (400 MHz, CDCl3) δ 9.04 (s, 1H), 8.76 (d, 2H) 8.68 (s, 1H), 7.94 (t, 1H), 7.777-7.718 (m, 3H), 7.61 (d, 1H), 2.90 (s, 3H), 2.76 (s, 3H). LC / MS (ESI+) m / z=423.1 [M+H]+.

[0649] Example 67. Preparation of 4-(2,4-difluorophenyl)-2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0650] The title compound (4.2 mg, yield: 4.2%) was prepared in the same manner as in Example 1, except that 3-(1-ethylpyrazol-4-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0651] 1H NMR (400 MHz, CDCl3) δ 8.88 (s, 1H), 8.62 (d, 1H), 7.92 (s, 1H), 7.89 (d, 1H), 7.85 (s, 1H), 7.67 (d, 1H), 7.53 (t, 1H), 7.14 (t, 1H), 7.04 (t, 1H), 4.26 (q, 2H), 2.89 (t, 3H), 2.76 (t, 3H), 1.58 (t, 3H). LC / MS (ESI+) m / z=443.1 [M+H]+.

[0652] Example 68. Preparation of 4-(2,4-difluorophenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0653] The title compound (7.1 mg, yield: 6.8%) was prepared in the same manner as in Example 1, except that 3-(1-isopropylpyrazol-4-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0654] 1H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 8.60 (d, 1H), 7.90-7.88 (m, 3H), 7.67 (d, 1H), 7.52 (t, 1H), 7.13 (t, 1H), 7.03 (t, 1H), 4.59-4.55 (m, 1H), 2.88 (s, 3H), 2.75 (s, 3H), 1.59 (d, 6H). LC / MS (ESI+) m / z=457.2 [M+H]+.

[0655] Example 69. Preparation of 4-(2,4-difluorophenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0656] The title compound (16.3 mg, yield: 15.2%) was prepared in the same manner as in Example 1, except that 3-(1-isobutylpyrazol-4-yl)phenylboronic acid (53 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0657] 1H NMR (400 MHz, CDCl3) δ 8.86 (s, 1H), 8.60 (d, 1H), 7.91 (s, 1H), 7.89 (d, 1H), 7.80 (s, 1H), 7.66 (d, 1H), 7.52 (t, 1H), 7.13 (t, 1H), 7.03 (t, 1H), 3.97 (d, 2H), 2.87 (s, 3H), 2.75 (s, 3H), 2.30-2.26 (m, 1H), 0.97 (d, 6H). LC / MS (ESI+) m / z=471.2 [M+H]+.

[0658] Example 70. Preparation of 2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-4-(2,4-difluorophenyl)-6,7-dimethylpteridine

[0659] The title compound (9.9 mg, yield: 9.5%) was prepared in the same manner as in Example 1, except that 3-(1-cyclopropylpyrazol-4-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0660] 1H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.61 (d, 1H), 7.91-7.86 (m, 3H), 7.65 (d, 1H), 7.52 (t, 1H), 7.13 (t, 1H), 7.03 (t, 1H), 3.68-3.65 (m, 1H), 2.88 (s, 3H), 2.75 (s, 3H), 1.23-1.20 (m, 2H), 1.10-1.05 (m, 2H). LC / MS (ESI+) m / z=455.2 [M+H]+.

[0661] Example 71. Preparation of 4-(2,4-difluorophenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0662] The title compound (18.7 mg, yield: 17.9%) was prepared in the same manner as in Example 1, except that 1-methyl-4-[3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (57 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0663] 1H NMR (400 MHz, CDCl3) δ 8.46 (s, 1H), 8.15 (s, 1H), 7.91-7.87 (m, 2H), 7.76 (s, 1H), 7.18 (s, 1H), 7.12 (t, 1H), 7.03 (t, 1H), 3.96 (s, 6H), 2.87 (s, 3H), 2.74 (s, 3H). LC / MS (ESI+) m / z=459.1 [M+H]+.

[0664] Example 72. Preparation of 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine

[0665] The title compound (6.7 mg, yield: 6.9%) was prepared in the same manner as in Example 1, except that 3-(pyridin-3-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0666] 1H NMR (400 MHz, CDCl3) δ 8.98 (s, 2H), 8.81 (d, 1H), 8.64 (s, 1H), 8.03 (d, 1H), 7.88 (q, 1H), 7.76 (d, 1H), 7.66 (t, 1H), 7.41 (t, 1H), 7.13 (t, 1H), 7.03 (t, 1H), 2.88 (s, 3H), 2.76 (s, 3H). LC / MS (ESI+) m / z=426.1 [M+H]+.

[0667] Example 73. Preparation of 2-([3,4-bipyridin]-5-yl)-4-(2,4-difluorophenyl)-6,7-dimethylpteridine

[0668] The title compound (11.5 mg, yield: 11.8%) was prepared in the same manner as in Example 1, except that [3,4'-bipyridin]-5-yl boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0669] 1H NMR (400 MHz, CDCl3) δ 10.05 (s, 1H), 9.25 (s, 1H), 9.04 (s, 1H), 8.82-8.73 (m, 2H), 7.93-7.89 (m, 1H), 7.67 (d, 2H), 7.15 (t, 1H), 7.06 (t, 1H), 2.91 (s, 3H), 2.79 (s, 3H). LC / MS (ESI+) m / z=427.1 [M+H]+.

[0670] Example 74. Preparation of 4-(4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorophenyl)morpholine

[0671] The title compound (5.3 mg, yield: 8.6%) was prepared in the same manner as in Example 17, except that 4-(4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorophenyl)morpholine (50 mg) prepared in Reference Example 34 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0672] 1H NMR (400 MHz, CDCl3) δ 8.70 (s, 1H), 8.50 (s, 1H), 7.91 (t, 2H), 7.80 (s, 1H), 7.48 (s, 1H), 6.90 (d, 1H), 6.75 (d, 1H), 3.99 (s, 1H), 3.92 (d, 4H), 3.36 (d, 4H), 2.88 (s, 3H), 2.78 (s, 3H), 2.51 (s, 3H). LC / MS (ESI+) m / z=510.2 [M+H]+.

[0673] Example 75. Preparation of 4-(3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)phenyl)morpholine

[0674] The title compound (4.8 mg, yield: 7.6%) was prepared in the same manner as in Example 68, except that 4-(4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorophenyl)morpholine (50 mg) prepared in Reference Example 34 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0675] 1H NMR (400 MHz, CDCl3) δ 8.91 (s, 1H), 8.65 (d, 1H), 7.92 (t, 3H), 7.68 (d, 1H), 7.54 (t, 1H), 6.89 (d, 1H), 6.75 (d, 1H), 4.608-4.575 (m, 1H), 3.92 (d, 4H), 3.36 (d, 4H), 2.88 (s, 1H), 2.78 (s, 3H), 1.61 (d, 6H). LC / MS (ESI+) m / z=524.2 [M+H]+.

[0676] Example 76. Preparation of 4-(4-(6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridin-4-yl)-3-fluorophenyl)morpholine

[0677] The title compound (3.2 mg, yield: 0.5%) was prepared in the same manner as in Example 64, except that 4-(4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorophenyl)morpholine (50 mg) prepared in Reference Example 34 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0678] 1H NMR (400 MHz, CDCl3) δ 9.10 (s, 1H), 9.88 (d, 1H) 8.72 (d, 2H), 7.92 (t, 1H), 7.82 (d, 1H), 7.694-7.656 (m, 3H), 6.90 (d, 1H), 6.76 (d, 1H), 3.92 (d, 4H), 3.36 (d, 4H), 3.89 (s, 1H), 2.79 (s, 1H). LC / MS (ESI+) m / z=468.2 [M+H]+.

[0679] Example 77. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0680] The title compound was prepared in a yield of 26.5% in the same manner as in Example 3, except that 3-(1-isobutylpyrazol-4-yl)phenylboronic acid (55 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0681] 1H NMR (400 MHz, MeOD) δ 8.77 (s, 1H), 8.44 (d, 1H), 8.10 (s, 1H), 7.95 (s, 1H), 7.88-7.85 (m, 1H), 7.75-7.70 (m, 1H), 7.53-7.44 (m, 3H), 4.02 (d, 2H), 2.83 (s, 3H), 2.71 (s, 3H), 2.05-2.02 (m, 1H), 0.99 (s, 3H), 0.94 (s, 3H). LC / MS (ESI+) m / z=487.1 [M+H]+.

[0682] Example 78. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0683] The title compound was prepared in a yield of 23.3% in the same manner as in Example 3, except that 3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenylboronic acid (66 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0684] 1H NMR (400 MHz, MeOD) δ 8.86 (s, 1H), 8.52 (d, 1H), 8.15 (s, 1H), 7.89 (s, 1H), 7.88-7.75 (m, 2H), 7.59-7.47 (m, 3H), 4.39 (t, 2H), 3.8 (t, 2H), 3.34 (s, 3H), 2.88 (s, 3H), 2.77 (s, 3H). LC / MS (ESI+) m / z=489.1 [M+H]+.

[0685] Example 79. Preparation of 2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine

[0686] The title compound was prepared in a yield of 9.8% in the same manner as in Example 13, except that 3-(1-ethylpyrazol-4-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0687] 1H NMR (400 MHz, MeOD) δ 8.84 (s, 1H), 8.50 (d, 1H), 8.14 (s, 1H), 7.96 (s, 1H), 7.77-7.74 (m, 2H), 7.58-7.55 (m, 1H), 7.25 (d, 1H), 7.16 (d, 1H), 4.25 (t, 2H), 2.86 (s, 3H), 2.750 (s, 3H), 2.53 (s, 3H), 1.28 (t, 3H). LC / MS (ESI+) m / z=440.2 [M+H]+.

[0688] Example 80. Preparation of 4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzamide

[0689] The title compound (3.2 mg, yield: 11.4%) was prepared in the same manner as in Example 17, except that 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorobenzamide (33 mg) prepared in Reference Example 35 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0690] 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 8.48 (s, 1H), 7.96 (t, 1H), 7.90 (s, 1H), 7.830-7.773 (m, 3H), 7.50 (s, 1H), 3.99 (s, 3H), 2.90 (s, 3H), 2.76 (s, 3H), 2.51 (s, 3H).LC / MS (ESI+) m / z=468.2 [M+H]+.

[0691] Example 81. Preparation of 3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzamide

[0692] The title compound (3.1 mg, yield: 10.7%) was prepared in the same manner as in Example 68, except that 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorobenzamide (35 mg) prepared in Reference Example 35 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0693] 1H NMR (400 MHz, CDCl3) δ 8.71 (s, 1H), 8.41 (d, 1H), 8.37 (s, 1H), 8.24 (s, 1H), 7.963-7.821 (m, 4H), 7.69 (s, 1H), 7.59 (t, 1H), 4.602-4.535 (m, 1H), 2.84 (s, 3H), 2.70 (s, 3H), 2.51 (s, 6H). LC / MS (ESI+) m / z=482.2 [M+H]+.

[0694] Example 82. Preparation of 4-fluoro-3-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzamide

[0695] The title compound (1.5 mg, yield: 5.2%) was prepared in the same manner as in Example 68, except that 3-(2-chloro-6,7-dimethylpteridin-4-yl)-4-fluorobenzamide (35 mg) prepared in Reference Example 36 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0696] 1H NMR (400 MHz, CDCl3) δ 8.88 (s, 1H), 8.60 (d, 1H), 8.33 (s, 1H), 8.16 (s, 1H), 7.9 (d, 1H), 7.70 (d, 1H), 7.55 (t, 1H), 7.39 (t, 1H), 7.14 (s, 1H), 6.85 (s, 1H), 4.611-4.560 (m, 1H), 2.91 (s, 3H), 2.76 (s, 3H), 2.05 (d, 6H). LC / MS (ESI+) m / z=482.2 [M+H]+.

[0697] Example 83. Preparation of 4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluoro-N,N-dimethylaniline

[0698] The title compound (4.2 mg, yield: 6.0%) was prepared in the same manner as in Example 17, except that 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluoro-N,N-dimethylaniline (45 mg) prepared in Reference Example 37 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0699] 1H NMR (400 MHz, CDCl3) δ 8.71 (s, 1H), 8.51 (s, 1H), 7.943-7.901 (m, 2H), 7.80 (s, 1H), 7.75 (s, 1H), 6.70 (d, 1H), 6.57 (d, 1H), 3.99 (s, 3H), 3.12 (s, 6H), 2.87 (s, 3H), 2.78 (s, 3H), 2.51 (s, 3H). LC / MS (ESI+) m / z=468.2 [M+H]+.

[0700] Example 84. Preparation of 3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)-N,N-dimethylaniline

[0701] The title compound (14.6 mg, yield: 10.1%) was prepared in the same manner as in Example 68, except that 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluoro-N,N-dimethylaniline (35 mg) prepared in Reference Example 37 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0702] 1H NMR (400 MHz, CDCl3) δ 8.92 (s, 1H), 8.66 (d, 1H), 7.642-7.903(m, 3H), 7.67 (d, 1H), 7.53 (t, 1H), 6.68 (d, 1H), 6.54 (d, 1H), 4.603-4.570 (m, 1H), 2.87 (s, 3H), 2.77 (s, 3H), 1.60 (d, 6H). LC / MS (ESI+) m / z=482.2 [M+H]+.

[0703] Example 85. Preparation of 4-(6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridin-4-yl)-3-fluoro-N,N-dimethylaniline

[0704] The title compound (19.8 mg, yield: 29.2%) was prepared in the same manner as in Example 64, except that 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluoro-N,N-dimethylaniline (35 mg) prepared in Reference Example 37 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0705] 1H NMR (400 MHz, CDCl3) δ 9.91 (s, 1H), 8.88 (d, 1H), 8.71 (d, 2H), 7.93 (t, 1H), 7.80 (d, 1H), 7.709-7.638 (m, 3H), 6.68 (d, 1H), 6.54 (d, 1H), 3.11 (s, 6H), 2.87 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=451.2 [M+H]+.

[0706] Example 86. Preparation of 4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine

[0707] The title compound was prepared in a yield of 15.5% in the same manner as in Example 3, except that 3-(pyridin-3-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0708] 1H NMR (400 MHz, MeOD) δ 9.01 (s, 1H), 8.87 (d, 1H), 8.83-8.878 (m, 1H), 8.24-8.20 (m, 1H), 7.78-7.50 (m, 4H), 7.48-7.29 (m, 3H), 2.89 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=442.1 [M+H]+.

[0709] Example 87. Preparation of 4-(2-fluoro-4-methylphenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0710] The title compound was prepared in a yield of 13.7% in the same manner as in Example 13, except that 3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenylboronic acid (60 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0711] 1H NMR (400 MHz, MeOD) δ 8.83 (s, 1H), 8.51 (d, 1H), 8.13 (s, 1H), 7.90 (s, 1H), 7.84-7.75 (m, 2H), 7.59-7.47 (m, 3H), 4.34 (t, 2H), 3.78 (t, 2H), 3.34 (s, 3H), 2.88 (s, 3H), 2.77 (s, 3H), 2.50 (s, 3H). LC / MS (ESI+) m / z=403.2 [M+H]+.

[0712] Example 88. Preparation of 4-(2-fluoro-4-methylphenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0713] The title compound was prepared in a yield of 17.6% in the same manner as in Example 13, except that 3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenylboronic acid (55 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0714] 1H NMR (400 MHz, MeOD) δ 8.47 (s, 1H), 8.12 (s, 1H), 8.07 (s, 1H), 7.95-7.92 (m, 1H), 7.77-7.75 (m, 1H), 7.43-7.23 (m, 3H), 3.97 (s, 3H), 3.94 (s, 3H), 2.88 (s, 3H), 2.77 (s, 3H), 2.54 (s, 3H). LC / MS (ESI+) m / z=455.5 [M+H]+.

[0715] Example 89. Preparation of 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine

[0716] The title compound was prepared in a yield of 5.5% in the same manner as in Example 13, except that 3-(pyridin-3-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0717] 1H NMR (400 MHz, MeOD) δ 9.01-8.99 (m, 2H), 8.73 (d, 1H), 8.61-8.59 (m, 1H), 8.25 (d, 1H), 7.89 (d, 1H), 7.77-7.70 (m, 2H), 7.59-7.57 (m, 1H), 7.25 (d, 1H), 7.18 (d, 1H), 2.88 (s, 3H), 2.77 (s, 3H), 2.53 (s, 3H). LC / MS (ESI+) m / z=422.2 [M+H]+.

[0718] Example 90. Preparation of 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine

[0719] The title compound was prepared in a yield of 9.8% in the same manner as in Example 13, except that 3-(pyridin-4-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0720] 1H NMR (400 MHz, MeOD) δ 9.07 (s, 1H), 8.82 (d, 1H), 8.68-8.65 (m, 2H), 8.02-7.89 (m, 3H), 7.78-7.69 (m, 2H), 7.50-7.46 (m, 2H), 2.90 (s, 3H), 2.73 (s, 3H), 2.50 (s, 3H). LC / MS (ESI+) m / z=422.2 [M+H]+.

[0721] Example 91. Preparation of 2-([3,4-bipyridin]-5-yl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine

[0722] The title compound was prepared in a yield of 14.3% in the same manner as in Example 13, except that [3,4'-bipyridin]-5-yl boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0723] 1H NMR (400 MHz, MeOD) δ 9.87 (s, 1H), 9.38 (s, 1H), 9.15 (s, 1H), 8.75-8.69 (m, 2H), 7.95-7.57 (m, 3H), 7.38-7.30 (m, 2H), 2.91 (s, 3H), 2.79 (s, 3H), 2.50 (s, 3H). LC / MS (ESI+) m / z=423.1 [M+H]+.

[0724] Example 92. Preparation of 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0725] The title compound was prepared in a yield of 8.2% in the same manner as in Example 13, except that 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (57 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0726] 1H NMR (400 MHz, MeOD) δ 9.31 (s, 1H), 8.68-8.62 (m, 3H), 7.72-7.70 (m, 2H), 7.32-7.18 (m, 3H), 2.86 (s, 3H), 2.74 (s, 3H), 2.53 (s, 3H). LC / MS (ESI+) m / z=412.1 [M+H]+.

[0727] Example 93. Preparation of 4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0728] The title compound was prepared in a yield of 13.9% in the same manner as in Example 11, except that 3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenylboronic acid (60 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0729] 1H NMR (400 MHz, MeOD) δ 8.80 (s, 1H), 8.48 (d, 1H), 8.09 (s, 1H), 7.97 (s, 1H), 7.78-7.72 (m, 3H), 7.55-7.52 (m, 1H), 4.38 (t, 2H), 3.81 (t, 2H), 3.34 (s, 3H), 2.85 (s, 3H), 2.73 (s, 3H). LC / MS (ESI+) m / z=532.2 [M+H]+.

[0730] Example 94. Preparation of 4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0731] The title compound was prepared in a yield of 12.2% in the same manner as in Example 11, except that 3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenylboronic acid (60 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0732] 1H NMR (400 MHz, MeOD) δ 8.41 (s, 1H), 8.22-7.98 (m, 4H), 7.88-7.72 (m, 1H), 7.23 (s, 1H), 3.96 (s, 3H), 3.92 (s, 3H), 2.83 (s, 3H), 2.70 (s, 3H). LC / MS (ESI+) m / z=509.1 [M+H]+.

[0733] Example 95. Preparation of 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine

[0734] The title compound was prepared in a yield of 5.8% in the same manner as in Example 11, except that 3-(pyridin-3-yl)phenylboronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0735] 1H NMR (400 MHz, MeOD) δ 9.01 (s, 1H), 8.78 (d, 1H), 8.70-8.65 (m, 2H), 8.12-8.00 (m, 2H), 7.87-7.85 (m, 2H), 7.79-7.68 (m, 3H), 2.91 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=476.1 [M+H]+.

[0736] Example 96. Preparation of 2-([3,4-bipyridin]-5-yl)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine

[0737] The title compound was prepared in a yield of 4.7% in the same manner as in Example 11, except that [3,4'-bipyridin]-5-yl boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0738] 1H NMR (400 MHz, MeOD) δ 9.92 (s, 1H), 9.29 (s, 1H), 9.04 (s, 1H), 8.82-8.72 (m, 2H), 7.94-7.55 (m, 3H), 7.25-7.03 (m, 2H), 2.91 (s, 3H), 2.79 (s, 3H). LC / MS (ESI+) m / z=477.1 [M+H]+.

[0739] Example 97. Preparation of 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0740] The title compound was prepared in a yield of 14.1% in the same manner as in Example 11, except that 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (55 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0741] 1H NMR (400 MHz, MeOD) δ 9.30 (s, 1H), 8.66-8.60 (m, 3H), 7.80-7.70 (m, 2H), 7.40-7.18 (m, 3H), 2.86 (s, 3H), 2.73 (s, 3H). LC / MS (ESI+) m / z=466.1 [M+H]+.

[0742] Example 98. Preparation of 2-([2,4-bipyridin]-4-yl)-4-(2,4-difluorophenyl)-6,7-dimethylpteridine

[0743] The title compound (35.3 mg, yield: 36.3%) was prepared in the same manner as in Example 1, except that [2,4'-bipyridin]-4-yl boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0744] 1H NMR (400 MHz, CDCl3) δ 9.10 (s, 1H), 8.94 (d, 1H), 8.77 (s, 2H), 8.62 (d, 1H), 8.08 (d, 2H), 7.88 (q, 1H), 7.15 (t, 1H), 7.05 (t, 1H), 2.91 (s, 3H), 2.79 (s, 3H). LC / MS (ESI+) m / z=427.1 [M+H]+.

[0745] Example 99. Preparation of 4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine

[0746] The title compound (11.7 mg, yield: 20.5%) was prepared in the same manner as in Example 68, except that 2-chloro-4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-6,7-dimethylpteridine (45 mg) prepared in Reference Example 38 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0747] 1H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 8.57 (d, 1H), 7.91 (d, 1H), 7.71 (d, 1H), 7.55 (d, 2H), 4.612-4.580 (m, 1H), 4.24 (s, 3H), 2.91 (s, 3H), 2.83 (s, 3H), 1.61 (d, 6H). LC / MS (ESI+) m / z=444.2 [M+H]+.

[0748] Example 100. Preparation of 4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine

[0749] The title compound (4.3 mg, yield: 8.1%) was prepared in the same manner as in Example 64, except that 2-chloro-4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-6,7-dimethylpteridine (45 mg) prepared in Reference Example 38 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0750] 1H NMR (400 MHz, CDCl3) δ 9.06 (s, 1H), 8.82 (d, 1H), 8.74 (d, 2H), 7.86 (d, 1H), 7.727-7.672 (m, 3H), 7.57 (d, 1H), 4.24 (s, 3H), 2.93 (s, 3H), 2.84 (s, 3H). LC / MS (ESI+) m / z=412.1 [M+H]+.

[0751] Example 101. Preparation of 4-(6,7-dimethyl-2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0752] The title compound (44.8 mg, yield: 30.5%) was prepared in the same manner as in Example 31, except that 1-cyclopropyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (95 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0753] 1H NMR (400 MHz, CDCl3) δ 8.82 (s, 1H) 8.58 (d, 1H), 7.97 (t, 1H), 7.88 (s, 2H), 7.71-7.50 (m, 4H), 3.69-3.66 (m, 1H), 2.89 (s, 3H), 2.74 (s, 3H), 1.25-1.07 (m, 4H). LC / MS (ESI+) m / z=463.2 [M+H]+.

[0754] Example 102. Preparation of 4-(6,7-dimethyl-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0755] The title compound (54.2 mg, yield: 35.5%) was prepared in the same manner as in Example 62, except that 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile (95 mg) prepared in Reference Example 18 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0756] 1H NMR (400 MHz, CDCl3) δ 8.81 (s, 1H), 8.55 (d, 1H), 7.96 (t, 1H), 7.89 (d, 2H), 7.69-7.64 (m, 2H), 7.57 (d, 1H), 7.49 (t, 1H), 4.34 (t, 2H), 3.79 (t, 2H), 3.36 (s, 3H), 2.89 (s, 3H), 2.71 (s, 3H). LC / MS (ESI+) m / z=480.2 [M+H]+.

[0757] Example 103. Preparation of 2-([2,4-bipyridin]-4-yl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine

[0758] The title compound was prepared in a yield of 7.6% in the same manner as in Example 13, except that [2,4'-bipyridin]-4-yl boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0759] 1H NMR (400 MHz, MeOD) δ 7.84-7.75 (m, 2H), 8.21 (d, 1H), 8.08-8.05 (m, 3H), 7.72-7.56 (m, 4H), 2.91 (s, 3H), 2.82 (s, 3H), 2.63 (s, 3H). LC / MS (ESI+) m / z=423.1 [M+H]+.

[0760] Example 104. Preparation of 4-(2-fluoro-4-chlorophenyl)-6,7-dimethyl-2-(3-trifluoromethyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0761] The title compound was prepared in a yield of 18.4% in the same manner as in Example 3, except that 1-methyl-4-[3-trifluoromethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (70.5 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0762] 1H NMR (400 MHz, MeOD) δ 9.07 (s, 1H), 8.79 (s, 1H), 8.24 (s, 1H), 7.95-7.73 (m, 2H), 7.90-7.88 (m, 1H), 7.52-7.48 (m, 2H), 4.01 (s, 3H), 2.90 (s, 3H), 2.79 (s, 3H). LC / MS (ESI+) m / z=513.1 [M+H]+.

[0763] Example 105. Preparation of 4-(6,7-dimethyl-2-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0764] The title compound (1.4 mg, yield: 1.9%) was prepared in the same manner as in Example 31, except that 1-methyl-4-[3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (55 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0765] 1H NMR (400 MHz, CDCl3) δ 8.66 (s, 1H), 8.30 (d, 1H), 7.98 (t, 1H), 7.90 (s, 1H), 7.81 (s, 1H), 7.73 (d, 1H), 7.62 (d, 1H), 7.36 (d, 1H), 4.00 (s, 3H), 2.92 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=454.1 [M+H]+.

[0766] Example 106. Preparation of 4-(6,7-dimethyl-2-(3-trifluoromethyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0767] The title compound (6.0 mg, yield: 18.7%) was prepared in the same manner as in Example 31, except that 1-methyl-4-[3-trifluoromethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole (74 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0768] 1H NMR (400 MHz, CDCl3) δ 9.00 (s, 1H), 8.84 (s, 1H), 7.96-7.93 (m, 2H), 7.85 (d, 2H), 7.72 (d, 1H), 7.60 (d, 1H), 3.99 (s, 3H), 2.91 (s, 3H), 2.76 (s, 3H). LC / MS (ESI+) m / z=504.1 [M+H]+.

[0769] Example 107. Preparation of 4-(6,7-dimethyl-2-(3-(4-methylpiperazin-1-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0770] The title compound (20.7 mg, yield: 28.6%) was prepared in the same manner as in Example 31, except that (3-(4-methylpiperazin-1-yl)phenylboronic acid (60 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0771] 1H NMR (400 MHz, CDCl3) δ 8.35 (s, 1H), 8.24 (d, 1H), 7.96 (t, 1H), 7.70 (d, 1H), 7.59 (d, 1H), 7.43 (t, 1H), 7.12 (d, 1H), 3.37 (s, 4H), 2.89 (s, 3H), 2.74 (s, 3H), 2.65 (s, 4H), 2.40 (s, 3H). LC / MS (ESI+) m / z=454.2 [M+H]+.

[0772] Example 108. Preparation of 4-(2-fluoro-4-nitrophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine

[0773] The title compound (14.3 mg, yield: 20.3%) was prepared in the same manner as in Example 17, except that 2-chloro-4-(2-fluoro-4-nitrophenyl)-6,7-dimethylpteridine (50 mg) prepared in Reference Example 39 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0774] 1H NMR (400 MHz, CDCl3) δ 8.64 (s, 1H), 8.45 (s, 1H), 8.29 (br d, 1H), 8.18 (br d, 1H), 8.05 (br t, 1H), 7.89 (s, 1H), 7.78 (s, 1H), 7.50 (s, 1H), 3.99 (s, 3H), 2.90 (s, 3H), 2.76 (s, 3H). LC / MS (ESI+) m / z=470.2 [M+H]+.

[0775] Example 109. Preparation of 4-(6,7-dimethyl-2-(3-methyl-5-(2-methylpyridin-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0776] The title compound (31.0 mg, yield: 35.2%) was prepared in the same manner as in Example 31, except that (3-methyl-5-(2-methylpyridin-4-yl)phenyl)boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0777] 1H NMR (400 MHz, CDCl3) δ 8.81 (brs, 1H), 8.64 (brs, 1H), 8.56 (br d, 1H), 7.98 (br t, 1H), 7.71 (br d, 1H), 7.65-7.56 (m, 2H), 7.51 (s, 1H), 2.90 (s, 3H), 2.76 (s, 3H), 2.66 (s, 3H), 2.55 (s, 3H). LC / MS (ESI+) m / z=461.1 [M+H]+.

[0778] Example 110. Preparation of 2-([2,4-bipyridin]-4-yl)-4-(2-fluoro-4-chlorophenyl)-6,7-dimethylpteridine

[0779] The title compound was prepared in a yield of 5.5% in the same manner as in Example 3, except that [2,4'-bipyridin]-4-yl boronic acid (50 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0780] 1H NMR (400 MHz, MeOD) δ 9.22 (s, 1H), 8.96-8.94 (m, 1H), 8.76-8.70 (m, 2H), 8.24-8.22 (m, 1H), 7.62-7.52 (m, 5H), 2.93 (s, 3H), 2.81 (s, 3H). LC / MS (ESI+) m / z=443.1 [M+H]+.

[0781] Example 111. Preparation of 4-[4-(difluoromethyl)-2-fluorophenyl]-6,7-dimethyl-2-[3-methyl-5-(pyridin-4-yl)phenyl]pteridine

[0782] 2-chloro-4-(2-fluoro-4-(difluoromethyl)phenyl)-6,7-dimethylpteridine (60 mg) prepared in Reference Example 40 and (3-methyl-5-(pyridin-4-yl)phenyl)boronic acid (45.3 mg) were dissolved in dioxane (2.0 mL) and purified water (0.5 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (7.2 mg) and cesium carbonate (115.4 mg) thereto, the mixture was stirred for 3 hours at 60°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 2) to prepare the title compound (3.4 mg, yield: 4.1%).

[0783] 1H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.69 (s, 3H), 7.95 (t, 1H), 7.66-7.65 (m, 3H), 7.55 (d, 1H), 7.46 (d, 1H), 6.78 (t, 1H), 2.89 (s, 3H), 2.76 (s, 3H), 2.56 (s, 3H). LC / MS (ESI+) m / z=472.2 [M+H]+.

[0784] Example 112. Preparation of 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(tetrahydrofuran-3-yl)phenyl)pteridine

[0785] The title compound was prepared in a yield of 6.9% in the same manner as in Example 13, except that (3-(tetrahydrofuran-3-yl)phenylboronic acid (45 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0786] 1H NMR (400 MHz, MeOD) δ 8.65-8.51 (m, 2H), 7.75-7.72 (t, 1H), 7.50-7.48 (m, 2H), 7.26-7.15 (m, 2H), 4.23-3.94 (m, 3H), 3.81-3.59 (m, 2H), 2.86 (s, 3H), 2.74 (s, 3H), 2.52 (s, 3H), 2.47-2.44 (m, 1H), 2.17-2.14 (m, 1H). LC / MS (ESI+) m / z=415.1 [M+H]+.

[0787] Example 113. Preparation of 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(tetrahydro-2H-pyran-4-yl)phenyl)pteridine

[0788] The title compound was prepared in a yield of 11.7% in the same manner as in Example 13, except that (3-(tetrahydro-2H-pyran-4-yl)phenylboronic acid (48 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0789] 1H NMR (400 MHz, MeOD) δ 8.59-8.50 (m, 2H), 7.76-7.72 (t, 1H), 7.50-7.48 (m, 2H), 7.26-7.15 (m, 2H), 4.11-4.09 (m, 2H), 3.66-3.61 (m, 2H), 2.97-2.94 (m, 1H), 2.87 (s, 3H), 2.75 (s, 3H), 2.53 (s, 3H), 1.93-1.89 (m, 4H). LC / MS (ESI+) m / z=429.2 [M+H]+.

[0790] Example 114. Preparation of 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0791] The title compound (20.0 mg, yield: 28.6%) was prepared in the same manner as in Example 1, except that 2-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (57 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0792] 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 8.67 (s, 1H), 8.60 (br d, 1H), 7.81-7.90 (m, 1H), 7.67 (s, 1H), 7.54 (br d, 1H), 7.15 (br t, 1H), 7.05 (br t, J=9.38 Hz, 1H), 2.87 (s, 3H), 2.75 (s, 3H), 2.67 (s, 3H). LC / MS (ESI+) m / z=430.1 [M+H]+.

[0793] Example 115. Preparation of 4-(6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridin-4-yl)-3-fluorobenzonitrile

[0794] The title compound (16.6 mg, yield: 23.3%) was prepared in the same manner as in Example 31, except that 2-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (62 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0795] 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 8.69-8.58 (m, 2H), 7.94 (br t, 1H), 7.72 (br d, 1H), 7.67 (s, 1H), 7.67 (s, 1H), 7.69-7.64 (m, 1H), 7.61 (br d, 1H), 7.54 (d, 1H), 2.89 (s, 3H), 2.75 (s, 3H), 2.68 (s, 3H). LC / MS (ESI+) m / z=437.1 [M+H]+.

[0796] Example 116. Preparation of 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0797] The title compound was prepared in a yield of 18.8% in the same manner as in Example 13, except that 2-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (51 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0798] 1H NMR (400 MHz, MeOD) δ 9.12-9.10 (s, 1H), 8.45-8.40 (m, 2H), 7.81-7.51 (m, 3H), 7.23-7.13 (m, 2H), 2.81 (s, 3H), 2.79 (s, 3H), 2.68 (s, 3H), 2.52 (s, 3H). LC / MS (ESI+) m / z=426.2 [M+H]+.

[0799] Example 117. Preparation of 4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-methyl-1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0800] The title compound was prepared in a yield of 28.5% in the same manner as in Example 13, except that 4-(3-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (51 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0801] 1H NMR (400 MHz, MeOD) δ 9.28 (s, 1H), 8.65 (s, 1H), 8.00-7.97 (m, 2H), 7.76-7.74 (m, 2H), 7.26-7.12 (m, 1H), 3.51 (s, 3H), 3.24 (s, 3H), 2.88 (s, 3H), 2.75 (s, 3H). LC / MS (ESI+) m / z=426.1 [M+H]+.

[0802] Example 118. Preparation of 4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0803] The title compound was prepared in a yield of 13.7% in the same manner as in Example 11, except that 2-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (62 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0804] 1H NMR (400 MHz, MeOD) δ 9.29 (s, 1H), 8.60 (s, 1H), 8.53 (d, 1H), 8.03 (t, 1H), 7.91 (s, 1H), 7.81-7.71 (m, 3H), 2.87 (s, 3H), 2.74 (s, 3H), 2.65 (s, 3H). LC / MS (ESI+) m / z=480.1 [M+H]+.

[0805] Example 119. Preparation of 4-(2-fluoro-4-chlorophenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0806] The title compound was prepared in a yield of 12.0% in the same manner as in Example 3, except that 2-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (54 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0807] 1H NMR (400 MHz, MeOD) δ 9.03 (s, 1H), 8.54-8.51 (m, 2H), 7.93-7.83 (m, 3H), 7.50-7.45 (m, 2H), 2.87 (s, 3H), 2.75 (s, 3H), 2.66 (s, 3H). LC / MS (ESI+) m / z=446.1 [M+H]+.

[0808] Example 120. Preparation of 4-(2-fluoro-4-chlorophenyl)-6,7-dimethyl-2-(3-methyl-1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0809] The title compound was prepared in a yield of 18.5% in the same manner as in Example 3, except that 4-(3-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)-1H-pyrazol-1-yl)pyridine (51 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0810] 1H NMR (400 MHz, MeOD) δ 9.12 (s, 1H), 8.66-8.64 (m, 2H), 7.98-7.96 (m, 2H), 7.82 (t, 2H), 7.64 (d, 2H), 2.86 (s, 3H), 2.75 (s, 3H), 2.41 (s, 3H). LC / MS (ESI+) m / z=446.1 [M+H]+.

[0811] Example 121. Preparation of 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0812] 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine (100 mg) prepared in Reference Example 41 and 3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenylboronic acid (107.8 mg) were dissolved in dioxane (3.0 mL) and purified water (1.0 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (13.4 mg) and cesium carbonate (213.2 mg) thereto, the mixture was stirred for 1 hour at 50°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 2) to prepare the title compound (6.8 mg, yield: 4.7%).

[0813] 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 8.31 (d, 1H), 7.88 (s, 1H), 7.80-7.74 (m, 3H), 7.31 (d, 2H), 7.16 (t, 1H), 7.08 (t, 1H), 3.98 (d, 3H), 2.84 (s, 3H), 2.49 (s, 3H). LC / MS (ESI+) m / z=446.1 [M+H]+.

[0814] Example 122. Preparation of 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(2-methylpyridin-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0815] The title compound (10.3 mg, yield: 6.9%) was prepared in the same manner as in Example 121, except that 4-[3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl]-2-methylpyridine (153.4 mg) was used instead of 3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenylboronic acid.

[0816] 1H NMR (400 MHz, CDCl3) δ 8.86 (s, 1H), 8.59 (d, 1H), 8.52 (d, 1H), 7.83 (s, 1H), 7.75 (q, 1H), 7.52 (s, 1H), 7.48-7.42 (m, 2H), 7.19 (t, 1H), 7.09 (t, 1H), 2.85 (s, 3H), 2.67 (s, 3H), 2.50 (s, 3H). LC / MS (ESI+) m / z=457.1 [M+H]+.

[0817] Example 123. Preparation of 4-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpyrido[2,3-d]pyrimidin-2-yl)-5-fluorophenyl)morpholine

[0818] The title compound (9.0 mg, yield: 6.1%) was prepared in the same manner as in Example 121, except that 4-[3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl]morpholine (150.7 mg) was used instead of 3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenylboronic acid.

[0819] 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.94 (d, 1H), 7.78 (s, 1H), 7.72 (q, 1H), 7.15 (t, 1H), 7.05 (t, 1H), 6.71 (d, 1H), 3.87 (s, 4H), 3.28 (s, 4H), 2.81 (s, 3H), 2.47 (s, 3H). LC / MS (ESI+) m / z=451.1 [M+H]+.

[0820] Example 124. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0821] The title compound was prepared in a yield of 4.2% in the same manner as in Example 121, except that 2-chloro-4-(4-chloro-2-fluorophenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine (65 mg) prepared in Reference Example 42 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine.

[0822] 1H NMR (400 MHz, MeOD) δ 8.67 (s, 1H), 8.18-8.09 (m, 2H), 7.95-7.97 (m, 2H), 7.85-7.83 (m, 1H), 7.57-7.49 (m, 3H), 2.83 (s, 3H), 2.53 (s, 3H), 2.19 (s, 3H). LC / MS (ESI+) m / z=462.1 [M+H]+.

[0823] Example 125. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(2-methylpyridin-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0824] The title compound was prepared in a yield of 7.0% in the same manner as in Example 122, except that 2-chloro-4-(4-chloro-2-fluorophenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine (70 mg) prepared in Reference Example 42 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine.

[0825] 1H NMR (400 MHz, MeOD) δ 8.83 (s, 1H), 8.61-8.49 (m, 2H), 8.00 (t, 2H), 7.73-7.42 (m, 4H), 7.57-7.49 (m, 2H), 2.83 (s, 3H), 2.78 (s, 3H), 2.68 (s, 3H). LC / MS (ESI+) m / z=473.1 [M+H]+.

[0826] Example 126. Preparation of (4-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-1H-pyrazol-1-yl)(1-methylpiperidin-4-yl)methanone

[0827] 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine (300 mg) prepared in Reference Example 1 and tert-butyl 4-[3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl]pyrazole-1-carboxylate (380 mg) were dissolved in dioxane (4.0 mL) and purified water (1.0 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (40.0 mg) and cesium carbonate (956 mg) thereto, the mixture was stirred for 1 hour at 50°C. The reaction mixture was cooled to room temperature, and, after adding dichloromethane thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was dissolved in dichloromethane (5.0 mL), and trifluoroacetic acid (0.4 mL) was added dropwise thereto. After that, the reaction solution was stirred for 1 hour at 50°C, then the residue obtained by vacuum concentrating the result was dissolved in N,N-dimethylformamide (2.0) mL, and after introducing diisopropylethylamine (90 mg) and 1-methylpiperidine-4-carbonyl chloride (55 mg) thereto, the mixture was stirred for 2 hours at room temperature. Ethyl acetate was added to the reaction mixture, and the reaction mixture was washed with an aqueous solution and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 30) to prepare the title compound (28.0 mg, yield: 31.7%).

[0828] 1H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 8.62 (s, 1H), 8.42 (br d, 1H), 8.14 (s, 1H), 7.93-7.83 (m, 1H), 7.30-7.50 (m, 1H), 7.16 (br t, 1H), 3.69-3.57 (m, 1H), 2.99 (br d, 2H), 2.91 (s, 3H), 2.79 (s, 3H), 2.35 (s, 3H), 2.22-2.11 (m, 2H), 2.10-2.03 (m, 2H), 2.03-1.91 (m, 2H). LC / MS (ESI+) m / z=558.1 [M+H]+.

[0829] Example 127. Preparation of 1-(4-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)phenyl)piperazin-1-yl)ethan-1-one

[0830] 2-chloro-4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridine (45 mg) prepared in Reference Example 3 and (3-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)boronic acid (85 mg) were dissolved in dioxane (2.0 mL) and purified water (0.5 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (11.4 mg) and cesium carbonate (136.11 mg) thereto, the mixture was stirred for 4 hours at 60°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was dissolved in dichloromethane (3.0 mL), and trifluoroacetic acid (158.7 mg) was added dropwise thereto. After that, the reaction solution was stirred for 2 hours at room temperature, then the residue obtained by vacuum concentrating the result was dissolved in N,N-dimethylformamide (2.0 mL), and after introducing diisopropylethylamine (90 mg) and acetyl chloride (55 mg) thereto, the mixture was stirred for 2 hours at 60°C. Ethyl acetate was added to the reaction mixture, and the reaction mixture was washed with an aqueous solution and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 30) to prepare the title compound (4.1 mg, yield: 6.6%).

[0831] 1H NMR (400 MHz, MeOD) δ 8.32 (s, 1H), 8.21 (d, 1H), 7.87 (t, 1H), 7.50-7.46 (m, 3H), 7.26 (d, 1H), 3.81-3.77 (m, 4H), 3.41-3.38 (m, 4H), 2.88 (s, 3H), 2.67 (s, 3H), 2.19 (s, 3H). LC / MS (ESI+) m / z=491.1 [M+H]+.

[0832] Example 128. Preparation of 3-fluoro-4-(2-(3-fluoro-5-(2-methylpyridin-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidin-4-yl)benzonitrile

[0833] The title compound was prepared in a yield of 7.2% in the same manner as in Example 122, except that 4-(2-chloro-6,7-dimethylpyrido[2,3-d]pyrimidin-4-yl)-3-fluorobenzonitrile (66 mg) prepared in Reference Example 43 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine.

[0834] 1H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.60 (br d, 1H), 8.51 (br d, 1H), 7.89 (t, 1H), 7.80-7.74 (m, 2H), 7.67 (br d, 1H), 7.54-7.46 (m, 2H), 7.43 (br d, 1H), 2.88 (s, 3H), 2.68 (s, 3H), 2.52 (s, 3H). LC / MS (ESI+) m / z=464.2 [M+H]+.

[0835] Example 129. Preparation of 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0836] The title compound (11.9 mg, yield: 26.2%) was prepared in the same manner as in Example 1, except that 1-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)-4-methylpiperazine (65 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0837] 1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.98-7.84 (m, 2H), 7.14 (br t, 1H), 7.04 (br t, 1H), 6.77 (br d, 1H), 3.39 (br s, 4H), 2.89 (s, 3H), 2.77 (s, 3H), 2.65 (br s, 4H), 2.41 (s, 3H). LC / MS (ESI+) m / z=465.1 [M+H]+.

[0838] Example 130. Preparation of 3-fluoro-4-(2-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0839] The title compound (29.6 mg, yield: 64.2%) was prepared in the same manner as in Example 31, except that 1-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)-4-methylpiperazine (71 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0840] 1H NMR (400 MHz, CDCl3) δ 8.13 (s, 1H), 8.03-7.84 (m, 2H), 7.71 (br d, 1H), 7.59 (br d, 1H), 6.77 (br d, 1H), 3.37 (br s, 4H), 2.89 (s, 3H), 2.75 (s, 3H), 2.64 (br s, 4H), 2.40 (s, 3H). LC / MS (ESI+) m / z=472.1 [M+H]+.

[0841] Example 131. Preparation of 3-fluoro-4-(2-(3-fluoro-4-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0842] The title compound (8.9 mg, yield: 12.0%) was prepared in the same manner as in Example 31, except that (3-fluoro-4-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)boronic acid (65 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0843] 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 8.34 (d, 1H), 8.32 (d, 1H), 7.96 (t, 1H), 7.67-7.75 (m, 2H), 7.65-7.54 (m, 2H), 4.02 (s, 3H), 2.90 (s, 3H), 2.76 (s, 3H), 2.42 (s, 3H). LC / MS (ESI+) m / z=468.1 [M+H]+.

[0844] Example 132. Preparation of 4-(4-(difluoromethyl)-2-fluorophenyl)-2-(3-fluoro-5-(4-(2-methoxyethyl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0845] The title compound (5.7 mg, yield: 6.0%) was prepared in the same manner as in Example 111, except that [3-fluoro-5-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]boronic acid (75 mg) was used instead of (3-methyl-5-(pyridin-4-yl)phenyl)boronic acid.

[0846] 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.94-7.90 (m, 2H), 7.53 (d, 1H), 7.44 (d, 1H), 6.77 (t, 1H), 6.74 (s, 1H), 3.58 (t, 2H), 3.39-3.36 (m, 7H), 2.88 (s, 3H), 2.75 (s, 3H), 2.71-2.65 (m, 6H). LC / MS (ESI+) m / z=541.2 [M+H]+.

[0847] Example 133. Preparation of 3-fluoro-4-(2-(3-fluoro-5-(4-isobutyrylpiperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0848] 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile (60 mg) prepared in Reference Example 18 and tert-butyl 4-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)piperazine-1-carboxylate (115 mg) were dissolved in dioxane (2.0 mL) and purified water (0.5 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (10.5 mg) and cesium carbonate (122.2 mg) thereto, the mixture was stirred for 2 hours at 50°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was dissolved in dichloromethane (3.0 mL), and trifluoroacetic acid (158.7 mg) was added dropwise thereto. After that, the reaction solution was stirred for 2 hours at room temperature, then the residue obtained by vacuum concentrating the result was dissolved in N,N-dimethylformamide (2.0 mL), and after introducing diisopropylethylamine (90 mg) and isobutyryl chloride (25 mg) thereto, the mixture was stirred for 2 hours at room temperature. Ethyl acetate was added to the reaction mixture, and the reaction mixture was washed with an aqueous solution and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 30) to prepare the title compound (7.6 mg, yield: 22.0%).

[0849] 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 8.00-7.89 (m, 2H), 7.72 (dd, J=1.25, 7.88 Hz, 1H), 7.62 (t, J=1.00 Hz, 1H), 6.79 (td, J=2.19, 11.26 Hz, 1H), 3.89-3.90 (m, 1H), 3.69-3.90 (m, 3H), 3.26-3.41 (m, 4H), 2.91 (s, 3H), 2.77 (s, 3H), 1.18-1.21 (m, 6H). LC / MS (ESI+) m / z=528.2 [M+H]+.

[0850] Example 134. Preparation of 4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine

[0851] The title compound (6.5 mg, yield: 8.0%) was prepared in the same manner as in Example 111, except that [1-(2-methyl-4-pyridyl)pyrazol-4-yl]boronic acid (54 mg) was used instead of (3-methyl-5-(pyridin-4-yl)phenyl)boronic acid.

[0852] 1H NMR (400 MHz, CDCl3) δ 9.00 (s, 1H), 8.65 (s, 1H), 8.59 (d, 1H), 7.90 (t, 1H), 7.65 (s, 1H), 7.54 (s, 2H), 7.45 (s, 1H), 6.77 (t, 1H), 2.86 (s, 3H), 2.73 (s, 3H), 2.66 (s, 3H). LC / MS (ESI+) m / z=462.1 [M+H]+.

[0853] Example 135. Preparation of 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-((1-methylazetidin-3-yl)methyl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0854] 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine (45 mg) prepared in Reference Example 1 and tert-butyl 4-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)phenyl)piperazine-1-carboxylate (100 mg) were dissolved in dioxane (2.0 mL) and purified water (0.5 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (10.0 mg) and cesium carbonate (110.0 mg) thereto, the mixture was stirred for 2 hours at 50°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was dissolved in dichloromethane (2.0 mL), and trifluoroacetic acid (120 mg) was added dropwise thereto. The reaction solution was stirred for 2 hours at room temperature, then an aqueous sodium bicarbonate solution was added thereto, and the reaction solution was extracted with dichloromethane and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was dissolved in methanol (1 mL) and dichloromethane (1 mL), and after adding N-methylazetidine-3-carboxaldehyde (20 mg) and sodium triacetoxyborohydride (115 mg) thereto, the mixture was stirred for 4 hours at room temperature. Dichloromethane was added to the reaction mixture, and the reaction mixture was washed with an aqueous sodium bicarbonate solution and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: dichloromethane / methanol=9 / 1) to prepare the title compound (23.0 mg, yield: 75.7%).

[0855] 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.96-7.83 (m, 2H), 7.17-6.97 (m, 2H), 6.79-6.71 (m, 1H), 3.52 (br t, 2H), 3.33 (t, 4H), 2.95-2.82 (m, 5H), 2.78-2.68 (m, 4H), 2.64 (d, 2H), 2.59 (t, 4H), 2.34 (s, 3H). LC / MS (ESI+) m / z=534.2 [M+H]+.

[0856] Example 136. Preparation of 3-fluoro-4-(2-(3-fluoro-5-(4-((1-methylazetidin-3-yl)methyl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0857] The title compound (25.0 mg, yield: 81.2%) was prepared in the same manner as in Example 135, except that 4-(2-chloro-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile (35 mg) prepared in Reference Example 18 was used instead of 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine.

[0858] 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 8.01-7.91 (m, 1H), 7.88 (br d, 1H), 7.73-7.65 (m, 1H), 7.58 (dd, 1H), 6.78-6.71 (m, 1H), 3.51 (t, 2H), 3.35-3.27 (m, 4H), 2.88 (t, 5H), 2.77-2.67 (m, 4H), 2.64 (br d, 2H), 2.61-2.55 (m, 4H), 2.32 (s, 3H). LC / MS (ESI+) m / z=541.2 [M+H]+.

[0859] Example 137. Preparation of 2-(4-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)piperazin-1-yl)-N,N-dimethylethan-1-amine

[0860] The title compound (2.1 mg, yield: 6.2%) was prepared in the same manner as in Example 135, except that 2-(dimethylamino)acetaldehyde (7.0 mg) was used instead of N-methylazetidine-3-carboxaldehyde.

[0861] 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.97-7.83 (m, 2H), 7.14 (t, 1H), 7.04 (t, 1H), 6.76 (td, 1H), 3.42-3.32 (m, 4H), 2.89 (s, 3H), 2.77 (s, 3H), 2.73-2.65 (m, 4H), 2.62-2.50 (m, 4H), 2.32 (s, 6H). LC / MS (ESI+) m / z=522.2 [M+H]+.

[0862] Example 138. Preparation of 3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylpiperidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0863] The title compound (1.1 mg, yield: 2.1%) was prepared in the same manner as in Example 136, except that N-methylpiperidin-3-one (13.0 mg) was used instead of N-methylazetidine-3-carboxaldehyde.

[0864] 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.96 (t, 1H), 7.91 (d, 1H), 7.72 (dd, J=1.25, 7.88 Hz, 1H), 7.60 (d, J=9.01 Hz, 1H), 6.75-6.80 (m, 1H), 3.31-3.38 (m, 4H), 2.91 (s, 4H), 2.75-2.83 (m, 8H), 2.29-2.46 (m, 5H), 1.97-2.08 (m, 4H), 1.33-1.39 (m, 3H). LC / MS (ESI+) m / z=555.2 [M+H]+.

[0865] Example 139. Preparation of tert-butyl (3S,5R)-4-(3-(4-(4-cyano-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-3,5-dimethylpiperazine-1-carboxylate

[0866] The title compound (318 mg, yield: 56.8%) was prepared in the same manner as in Example 31, except that tert-butyl (3S,5R)-4-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)phenyl)-3,5-dimethylpiperazine-1-carboxylate (255 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0867] 1H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 8.16 (br d, 1H), 7.95 (t, 1H), 7.72 (dd, 1H), 7.60 (dd, 1H), 6.93 (br d, 1H), 3.80 (br s, 2H), 3.44-3.32 (m, 2H), 3.13 (dd, 2H), 2.90 (s, 3H), 2.76 (s, 3H), 2.04 (s, 2H), 1.25 (s, 10H), 0.96 (d, 6H). LC / MS (ESI+) m / z=586.3 [M+H]+.

[0868] Example 140. Preparation of 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine

[0869] The title compound (5.2 mg, yield: 5.7%) was prepared in the same manner as in Example 121, except that [3-fluoro-5-(4-methylpiperazin-1-yl)phenyl]boronic acid (70.1 mg) was used instead of (3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenylboronic acid.

[0870] 1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.92 (d, 1H), 7.79 (d, 1H), 7.73 (q, 1H), 7.16 (t, 1H), 7.06 (t, 1H), 6.73 (d, 1H), 3.36 (t, 4H), 2.82 (s, 3H), 2.60 (t, 4H), 2.48 (s, 3H), 2.37 (s, 3H). LC / MS (ESI+) m / z=464.2 [M+H]+.

[0871] Example 141. Preparation of 3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0872] The title compound (1.5 mg, yield: 2.8%) was prepared in the same manner as in Example 136, except that N-methylpiperidin-4-one (13.3 mg) was used instead of N-methylazetidine-3-carboxaldehyde.

[0873] 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 7.96 (t, 1H), 7.91 (d, 1H), 7.72 (dd, 1H), 7.60 (d, 1H), 6.77 (d, 1H), 3.40-3.33 (m, 4H), 2.96 (br d, 2H), 2.91 (s, 3H), 2.79-2.75 (m, 6H), 2.38-2.25 (m, 4H), 2.10-1.93 (m, 3H), 1.88 (br d, 2H), 1.75-1.64 (m, 2H). LC / MS (ESI+) m / z=555.2 [M+H]+.

[0874] Example 142. Preparation of 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(4-(pyridin-4-yl)-1H-pyrazol-1-yl)pteridine

[0875] 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine (30 mg) prepared in Reference Example 1 and 4-(1H-pyrazol-4-yl)pyridine (28.4 mg) were dissolved in dioxane (0.5 mL), and after adding tris(dibenzylideneacetone)dipalladium (0) (4.6 mg), cesium carbonate (95.61 mg) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (6.1 mg) thereto, the mixture was stirred for 1 hour at 50°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 30) to prepare the title compound (9.0 mg, yield: 22.2%).

[0876] 1H NMR (400 MHz, CDCl3) δ 9.32 (s, 1H), 8.67 (d, 2H), 8.28 (s, 1H), 7.91 (dt, 1H), 7.53 (d, 2H), 7.17-7.11 (m, 1H), 2.91 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=416.1 [M+H]+.

[0877] Example 143. Preparation of 8-(2,4-difluorophenyl)-2,3-dimethyl-6-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazine

[0878] 8-chloro-2,3-dimethyl-6-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazine (100 mg) prepared in Reference Example 44 and 2,4-difluorophenylboronic acid (67.5 mg) were dissolved in dioxane (3.0 mL) and purified water (1.0 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (10.4 mg) and cesium carbonate (185.8 mg) thereto, the mixture was stirred for 3 hours at 60°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 2) to prepare the title compound (3.4 mg, yield: 4.1%).

[0879] 1H NMR (400 MHz, CDCl3) δ 8.95 (s, 1H), 8.60 (d, 1H), 8.42 (s, 1H), 7.89 (s, 1H), 7.65 (d, 1H), 7.60 (q, 1H), 7.51 (d, 1H), 7.10-7.01 (m, 2H), 2.83 (s, 3H), 2.70 (s, 3H), 2.66 (s, 3H). LC / MS (ESI+) m / z=429.2 [M+H]+.

[0880] Example 144. Preparation of 8-(4-chloro-2-fluorophenyl)-6-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-2,3-dimethylpyrido[2,3-b]pyrazine

[0881] The title compound (16.6 mg, yield: 13.4%) was prepared in the same manner as in Example 143, except that 8-chloro-6-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-2,3-dimethylpyrido[2,3-b]pyrazine (100 mg) prepared in Reference Example 45 and 4-chloro-2-fluorophenylboronic acid (56 mg) were used instead of 8-chloro-2,3-dimethyl-6-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazine and 2,4-difluorophenylboronic acid.

[0882] 1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 7.70 (s, 1H), 7.53 (t, 1H), 7.35-7.25 (m, 3H), 6.70 (d, 1H), 3.34 (s, 4H), 2.82 (s, 3H), 2.72 (s, 3H), 2.56 (s, 4H), 2.36 (s, 3H). LC / MS (ESI+) m / z=480.1 [M+H]+.

[0883] Example 145. Preparation of 4-(2-(3-(1-acetylpiperidin-3-yl)-5-methylphenyl)-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile

[0884] The title compound (43.7 mg, yield: 55.4%) was prepared in the same manner as in Example 31, except that 1-(3-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)piperidin-1-yl)ethan-1-one (155 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0885] 1H NMR (400 MHz, CDCl3) δ 8.49-8.38 (m, 2H), 8.01-7.92 (m, 1H), 7.71 (d, 1H), 7.58 (dd, 1H), 7.23 (br s, 1H), 4.85-4.68 (m, 1H), 3.90 (br t, 1H), 3.23 (t, 1H), 2.89-2.68 (m, 6H), 2.66-2.56 (m, 1H), 2.52-2.40 (m, 3H), 2.12 (s, 2H), 2.15 (s, 2H), 1.99-1.73 (m, 1H), 1.70-1.52 (m, 1H). LC / MS (ESI+) m / z=495.2 [M+H]+.

[0886] Example 146. Preparation of 4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(2-methyl-6-(4-methylpiperazin-1-yl)pyridin-4-yl)pteridine

[0887] The title compound (3.0 mg, yield: 3.6%) was prepared in the same manner as in Example 111, except that 1-methyl-4-(6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)pyridin-2-yl)piperazine (95 mg) was used instead of (3-methyl-5-(pyridin-4-yl)phenyl)boronic acid.

[0888] 1H NMR (400 MHz, CDCl3) δ 7.92 (t, 1H), 7.78 (s, 2H), 7.54 (d, 1H), 7.45 (d, 1H), 6.77 (t, 1H), 3.74 (s, 4H), 2.89 (s, 3H), 2.75 (s, 3H), 2.61 (s, 4H), 2.53 (s, 3H), 2.40 (s, 3H). LC / MS (ESI+) m / z=494.2 [M+H]+.

[0889] Example 147. Preparation of 4-(2-(3-(1-acetylpyrrolidin-3-yl)-5-methylphenyl)-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile

[0890] The title compound (18.4 mg, yield: 24.4%) was prepared in the same manner as in Example 31, except that 1-(3-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)pyrrolidin-1-yl)ethan-1-one (55 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0891] 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 8.47 (s, 1H), 7.93-7.84 (m, 1H), 7.24 (br d, 1H), 7.15 (br t, 1H), 4.17-4.06 (m, 1H), 3.98-3.83 (m, 1H), 3.63-3.43 (m, 3H), 2.88 (d, 3H), 2.76 (d, 2H), 2.80-2.73 (m, 1H), 2.48 (d, 3H), 2.30-2.14 (m, 1H), 2.12 (d, 3H). LC / MS (ESI+) m / z=474.2 [M+H]+.

[0892] Example 148. Preparation of 1-(5-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)ethan-1-one

[0893] The title compound was prepared in a yield of 23.1% in the same manner as in Example 127, except that tert-butyl 5-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (125 mg) was used instead of (3-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)boronic acid.

[0894] 1H NMR (400 MHz, MeOD) δ 7.95-7.79 (m, 3H), 7.13 (t, 1H), 7.06-7.04 (m, 1H), 6.41 (d, 1H), 3.69-3.66 (m, 4H), 3.43-3.40 (m, 4H), 3.37-3.35 (m, 2H), 2.89 (s,3 H), 2.78 (s, 3H), 2.05-2.03 (m, 2H), 0.96-0.94 (m, 9H). LC / MS (ESI+) m / z=535.1 [M+H]+.

[0895] Example 149. Preparation of 1-(3-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)piperidin-1-yl)ethan-1-one

[0896] The title compound (30.0 mg, yield: 91.6%) was prepared in the same manner as in Example 1, except that 1-(3-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)piperidin-1-yl)ethan-1-one (45 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0897] 1H NMR (400 MHz, CDCl3) δ 8.45 (s, 1H), 8.35 (br t, 1H), 7.88 (q, 1H), 7.18-7.00 (m, 3H), 4.87-4.70 (m, 1H), 3.99-3.85 (m, 1H), 3.27-3.04 (m, 1H), 2.93-2.58 (m, 8H), 2.15 (d, 4H), 1.94-1.74 (m, 2H), 1.73-1.47 (m, 1H). LC / MS (ESI+) m / z=492.2 [M+H]+.

[0898] Example 150. Preparation of 3-fluoro-4-(2-(3-methyl-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0899] The title compound (7.5 mg, yield: 10.1%) was prepared in the same manner as in Example 31, except that 1-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)-4-methylpiperazine (55 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0900] 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 8.10 (s, 1H), 7.96 (t, 1H), 7.71 (dd, 1H), 7.59 (dd, 1H), 6.96 (s, 1H), 3.39-3.32 (m, 4H), 2.89 (s, 3H), 2.78-2.70 (m, 3H), 2.67-2.60 (m, 4H), 2.47-2.42 (m, 3H), 2.40 (s, 3H). LC / MS (ESI+) m / z=468.2 [M+H]+.

[0901] Example 151. Preparation of 2-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)phenyl)hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one

[0902] The title compound (1.7 mg, yield: 2.2%) was prepared in the same manner as in Example 1, except that (3-(6-oxohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)phenylboronic acid (55 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0903] 1H NMR (400 MHz, CDCl3) δ 8.37 (s, 1H), 8.31 (d, 1H), 7.92-7.82 (m, 1H), 7.43 (t, 1H), 7.15-7.07 (m, 2H), 7.03 (dt, 1H), 4.20-4.14 (m, 1H), 3.93 (dd, 11.82 Hz, 1H), 3.86-3.74 (m, 2H), 3.16-3.03 (m, 1H), 2.87 (s, 3H), 2.74 (s, 3H), 2.56 (t, 1H), 2.50-2.43 (m, 2H), 2.34-2.21 (m, 1H), 1.79-1.66 (m, 1H). LC / MS (ESI+) m / z=487.2 [M+H]+.

[0904] Example 152. Preparation of 4-(2-(3-(1-acetylpyrrolidin-3-yl)-5-fluorophenyl)-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile

[0905] The title compound (51.6 mg, yield: 66.8%) was prepared in the same manner as in Example 31, except that 1-(3-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)pyrrolidin-1-yl)ethan-1-one (55 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0906] 1H NMR (400 MHz, CDCl3) δ 8.44 (d, 1H), 8.34-8.27 (m, 1H), 7.94 (t, 1H), 7.70 (d, 1H), 7.61-7.56 (m, 1H), 7.11 (br t, 1H), 4.11-4.03 (m, 1H), 3.97-3.91 (m, 1H), 3.84 (br d, 1H), 3.74-3.67 (m, 1H), 3.62-3.46 (m, 3H), 2.89 (d, 3H), 2.75 (d, 3H), 2.51-2.33 (m, 1H), 2.25-2.12 (m, 1H), 2.10 (s, 3H). LC / MS (ESI+) m / z=485.2 [M+H]+.

[0907] Example 153. Preparation of 4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(4-methylpiperazin-1-yl)phenyl)pteridine

[0908] The title compound (21.9 mg, yield: 5.0%) was prepared in the same manner as in Example 111, except that 1-methyl-4-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)piperazine (336 mg) was used instead of (3-methyl-5-(pyridin-4-yl)phenyl)boronic acid.

[0909] 1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 8.10 (s, 1H), 7.93 (t, 1H), 7.52 (d, 1H), 7.43 (d, 1H), 6.93 (s, 1H), 6.76 (t, 1H), 3.34 (s, 4H), 2.86 (s, 3H), 2.72 (s, 3H), 2.62 (s, 4H), 2.43 (s, 3H), 2.37 (s, 3H). LC / MS (ESI+) m / z=493.2 [M+H]+.

[0910] Example 154. Preparation of 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(1-methylpyrrolidin-3-yl)phenyl)-6,7-dimethylpteridine

[0911] The title compound (4.4 mg, yield: 30.7%) was prepared in the same manner as in Example 1, except that 3-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)-1-methylpyrrolidine (35 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0912] 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 8.30 (d, 1H), 7.93-7.85 (m, 1H), 7.24 (d, 1H), 7.15 (dt, 1H), 7.05 (dt, 1H), 3.62-3.51 (m, 1H), 3.09 (t, 1H), 2.91-2.69 (m, 9H), 2.63-2.58 (m, 1H), 2.49-2.39 (m, 4H), 2.04-1.93 (m, 1H). LC / MS (ESI+) m / z=450.2 [M+H]+.

[0913] Example 155. Preparation of 1-(6-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-2,6-diazaspiro[3.3]heptan-2-yl)-3,3-dimethylbutan-1-one

[0914] The title compound was prepared in a yield of 23.1% in the same manner as in Example 127, except that tert-butyl 6-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (120 mg) was used instead of (3-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)boronic acid, and 3,3-dimethylbutanoyl chloride (35 mg) was used instead of acetyl chloride.

[0915] 1H NMR (400 MHz, MeOD) δ 7.95-7.79 (m, 3H), 7.13 (t, 1H), 7.06-7.04 (m, 1H), 6.41 (d, 1H), 3.69-3.66 (m, 4H), 3.43-3.40 (m, 4H), 3.37-3.35 (m, 2H), 2.89 (s,3 H), 2.78 (s, 3H), 2.05-2.03 (m, 2H), 0.96-0.94 (m, 9H). LC / MS (ESI+) m / z=535.1 [M+H]+.

[0916] Example 156. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(6-isopropyl-2,6-diazaspiro[3.3]heptan-2-yl)phenyl)-6,7-dimethylpteridine

[0917] The title compound was prepared in a yield of 31.8% in the same manner as in Example 155, except that 2-iodopropane (118.4 mg) was used instead of 3,3-dimethylbutanoyl chloride.

[0918] 1H NMR (400 MHz, MeOD) δ 7.87-7.65 (m, 2H), 7.48 (s, 1H), 7.50-7.45 (m, 2H), 6.44-6.41 (m, 1H), 4.12 (s, 4H), 3.78-3.76 (s, 4H), 2.93 (s, 3H), 2.88-2.87 (m,1H), 2.76 (s, 3H), 0.94 (d, 6H). LC / MS (ESI+) m / z=521.2 [M+H]+.

[0919] Example 157. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(1-isopropylpiperidin-4-yl)phenyl)-6,7-dimethylpteridine

[0920] The title compound was prepared in a yield of 12.3% in the same manner as in Example 156, except that tert-butyl 4-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)piperidine-1-carboxylate (115 mg) was used instead of tert-butyl 6-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)-2,6-diazaspiro[3.3]heptane-2-carboxylate.

[0921] LC / MS (ESI+) m / z=508.2 [M+H]+.

[0922] Example 158. Preparation of 1-(4-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)piperidin-1-yl)ethan-1-one

[0923] The title compound was prepared in a yield of 6.6% in the same manner as in Example 127, except that tert-butyl 4-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)piperidine-1-carboxylate (115 mg) was used instead of (3-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)boronic acid.

[0924] LC / MS (ESI+) m / z=508.2 [M+H]+.

[0925] Example 159. Preparation of 3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylazetidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0926] The title compound (4.4 mg, yield: 28.2%) was prepared in the same manner as in Example 136, except that N-methylazetidin-3-one (20.0 mg) was used instead of N-methylazetidine-3-carboxaldehyde.

[0927] 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.99-7.88 (m, 2H), 7.71 (dd, 1H), 7.60 (dd, 1H), 6.77 (td, 1H), 3.66-3.53 (m, 2H), 3.42-3.24 (m, 4H), 3.12-2.96 (m, 3H), 2.91 (s, 3H), 2.76 (s, 2H), 2.78-2.73 (m, 1H), 2.60-2.45 (m, 4H), 2.42 (s, 3H). LC / MS (ESI+) m / z=527.2 [M+H]+.

[0928] Example 160. Preparation of 4-(6,7-dimethyl-2-(3-morpholino-5-(trifluoromethyl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0929] The title compound (8.2 mg, yield: 16.7%) was prepared in the same manner as in Example 31, except that (3-morpholino-5-(trifluoromethyl)phenyl)boronic acid (40 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0930] 1H NMR (400 MHz, CDCl3) δ 8.50 (br d, 2H), 7.97 (t, 1H), 7.73 (dd, 1H), 7.61 (dd, 1H), 3.97-3.89 (m, 4H), 3.41-3.33 (m, 4H), 2.92 (s, 3H), 2.78 (s, 3H). LC / MS (ESI+) m / z=509.2 [M+H]+.

[0931] Example 161. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(5-isopropyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-6,7-dimethylpteridine

[0932] The title compound was prepared in a yield of 22.8% in the same manner as in Example 156, except that (3-(5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-5-fluorophenyl)boronic acid (125 mg) was used instead of tert-butyl 6-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)-2,6-diazaspiro[3.3]heptane-2-carboxylate.

[0933] 1H NMR (400 MHz, MeOD) δ 7.89-7.70 (m, 4H), 7.50-7.46 (m, 1H), 6.66 (d, 1H), 5.68- 5.66 (m, 1H), 4.62-4.60 (m, 1H), 4.37-4.35 (m, 2H), 3.96-3.94 (m, 1H), 3.66-3.63 (m, 2H), 2.88 (s, 3H), 2.77 (s, 3H), 2.22-2.20 (m, 2H), 1.37-1.35 (s, 6H). LC / MS (ESI+) m / z=521.2 [M+H]+.

[0934] Example 162. Preparation of 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-isopropylpiperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0935] 2-chloro-4-(2,4-difluorophenyl)-6,7-dimethylpteridine (60 mg) prepared in Reference Example 1 and (3-(4-(tert-butoxycarbonyl)piperazin-1-yl)-5-fluorophenyl)boronic acid (95 mg) were dissolved in dioxane (2.0 mL) and purified water (0.5 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (11.4 mg) and cesium carbonate (136.11 mg) thereto, the mixture was stirred for 4 hours at 60°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was dissolved in dichloromethane (3.0 mL), and trifluoroacetic acid (158.7 mg) was added dropwise thereto. After that, the reaction solution was stirred for 2 hours at room temperature, then the residue obtained by vacuum concentrating the result was dissolved in N,N-dimethylformamide (2.0 mL), and after introducing diisopropylethylamine (90 mg) and 2-iodopropane (35 mg) thereto, the mixture was stirred for 2 hours at 60°C. Ethyl acetate was added to the reaction mixture, and the reaction mixture was washed with an aqueous solution and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate=1 / 30) to prepare the title compound in a yield of 76.2%.

[0936] 1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.96-7.84 (m, 2H), 7.14 (dt, 1H), 7.04 (dt, 1H), 6.77 (td, 1H), 3.41-3.33 (m, 4H), 2.89 (s, 3H), 2.83-2.70 (m, 7H), 1.13 (d, 6H). LC / MS (ESI+) m / z=493.2 [M+H]+.

[0937] Example 163. Preparation of 1-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-N,N-dimethylazetidin-3-amine

[0938] The title compound (9.5 mg, yield: 20.9%) was prepared in the same manner as in Example 1, except that 1-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)-N,N-dimethylazetidin-3-amine (45 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0939] 1H NMR (400 MHz, CDCl3) δ 7.91-7.80 (m, 2H), 7.65 (s, 1H), 7.14 (dt, 1H), 7.04 (dt, 1H), 6.32 (td, 1H), 4.09 (t, 2H), 3.84-3.76 (m, 2H), 3.30 (q, 1H), 2.89 (s, 2H), 2.77 (s, 2H), 2.25 (s, 6H). LC / MS (ESI+) m / z=465.2 [M+H]+.

[0940] Example 164. Preparation of 4-(2,4-difluorophenyl)-6,7-dimethyl-2-(4-(2-methylpyridin-4-yl)-1H-pyrazol-1-yl)pteridine

[0941] The title compound (4.7 mg, yield: 11.2%) was prepared in the same manner as in Example 142, except that 2-methyl-4-(1H-pyrazol-4-yl)pyridine (16.6 mg) was used instead of 4-(1H-pyrazol-4-yl)pyridine.

[0942] 1H NMR (400 MHz, CDCl3) δ 9.30 (s, 1H), 8.56 (d, 1H), 8.27 (s, 1H), 7.91 (dt, 1H), 7.42 (s, 1H), 7.35 (d, 1H), 7.14 (t, 1H), 7.04 (t, 1H), 2.91 (s, 3H), 2.78 (s, 3H), 2.64 (s, 3H). LC / MS (ESI+) m / z=430.2 [M+H]+.

[0943] Example 165. Preparation of 3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylpyrrolidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile

[0944] The title compound (3.7 mg, yield: 7.2%) was prepared in the same manner as in Example 136, except that N-methylpyrrolidin-3-one (113.7 mg) was used instead of N-methylazetidine-3-carboxaldehyde.

[0945] 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.96 (t, 1H), 7.91 (d, 1H), 7.71 (dd, 1H), 7.60 (dd, 1H), 6.77 (td,, 1H), 3.37 (t, 4H), 3.10-2.93 (m, 1H), 2.92-2.86 (m, 3H), 2.90-2.84 (m, 1H), 2.76 (s, 3H), 2.74-2.67 (m, 2H), 2.66-2.58 (m, 2H), 2.58-2.52 (m, 1H), 2.49-2.38 (m, 4H), 2.13-2.05 (m, 1H), 1.84 (ddd, 2H). LC / MS (ESI+) m / z=541.2 [M+H]+.

[0946] Example 166. Preparation of 4-(6,7-dimethyl-2-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile

[0947] The title compound (4.2 mg, yield: 8.4%) was prepared in the same manner as in Example 31, except that 1-methyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)-5-(trifluoromethyl)phenyl)piperazine (45 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0948] 1H NMR (400 MHz, CDCl3) δ 8.50 (s, 1H), 8.47 (s, 1H), 8.00-7.94 (m, 1H), 7.73 (dd,1H), 7.61 (dd, 1H), 7.30 (s, 1H), 3.45-3.39 (m, 4H), 2.92 (s, 3H), 2.77 (s. 3H), 2.66-2.63 (m, 4H), 2.41 (s, 3H). LC / MS (ESI+) m / z=522.2.

[0949] Example 167. Preparation of 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-(1-methylazetidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0950] The title compound (32.1 mg, yield: 12.5%) was prepared in the same manner as in Example 135, except that N-methylazetidin-3-one (75 mg) was used instead of N-methylazetidine-3-carboxaldehyde.

[0951] 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 7.98-7.83 (m, 2H), 7.13 (t, 1H), 7.04 (t, 1H), 6.76 (td, 1H), 3.59 (t, 2H), 3.40-3.33 (m, 4H), 3.08-2.96 (m, 3H), 2.89 (s, 3H), 2.76 (s, 3H), 2.55-2.46 (m, 4H), 2.41 (s, 3H). LC / MS (ESI+) m / z=520.3 [M+H]+.

[0952] Example 168. Preparation of 1-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-N,N-dimethylazetidin-3-amine

[0953] The title compound was prepared in a yield of 21.8% in the same manner as in Example 3, except that 1-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)-N,N-dimethylazetidin-3-amine (57 mg) was used instead of 1-methyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)phenyl]pyrazole.

[0954] 1H NMR (400 MHz, MeOD) δ 7.70-7.42 (m, 3H), 7.16-7.05 (m, 2H), 6.31 (d, 1H), 4.15-4.09 (m, 4H), 3.72-3.70 (m, 1H), 2.88 (s, 3H), 2.77 (s, 3H), 2.25 (s, 6H). LC / MS (ESI+) m / z=481.2 [M+H]+.

[0955] Example 169. Preparation of 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-(1-methylpyrrolidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0956] The title compound (6.1 mg, yield: 27.1%) was prepared in the same manner as in Example 135, except that N-methylpyrrolidin-3-one (35.0 mg) was used instead of N-methylazetidine-3-carboxaldehyde.

[0957] 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 7.96-7.83 (m, 2H), 7.14 (t, 1H), 7.07-7.01 (m, 1H), 6.76 (td, 1H), 3.37 (t, 4H), 3.05-2.94 (m, 1H), 2.91-2.83 (m, 4H), 2.77 (s, 3H), 2.74-2.68 (m, 2H), 2.67-2.57 (m, 2H), 2.57-2.50 (m, 1H), 2.45-2.35 (m, 4H), 2.14-2.03 (m, 1H), 1.95-1.74 (m, 2H). LC / MS (ESI+) m / z=534.2 [M+H]+.

[0958] Example 170. Preparation of 4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0959] The title compound (9.0 mg, yield: 7.4%) was prepared in the same manner as in Example 135, except that N-methylpiperidin-4-one (35.0 mg) was used instead of N-methylazetidine-3-carboxaldehyde.

[0960] 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.97-7.84 (m, 2H), 7.14 (t, 1H), 7.04 (t, 1H), 6.76 (td, 1H), 3.40-3.33 (m, 4H), 2.96 (br d, 2H), 2.89 (s, 3H), 2.80-2.72 (m, 7H), 2.39-2.27 (m, 4H), 2.05-1.95 (m, 2H), 1.88 (br d, 2H), 1.67 (dq, 2H). LC / MS (ESI+) m / z=548.2 [M+H]+.

[0961] Example 171. Preparation of 4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(4-(1-methylazetidin-3-yl)piperazin-1-yl)phenyl)pteridine

[0962] 2-chloro-4-(2-fluoro-4-(difluoromethyl)phenyl)-6,7-dimethylpteridine (60 mg) prepared in Reference Example 40 and tert-butyl 4-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoboran-2-yl)phenyl)piperazine-1-carboxylate (105 mg) were dissolved in dioxane (2.0 mL) and purified water (0.5 mL), and after adding palladium di[1,1'-bis(diphenylphosphino)ferrocene]dichloride·dichloromethane (10.0 mg) and cesium carbonate (110.0 mg) thereto, the mixture was stirred for 2 hours at 50°C. The reaction mixture was cooled to room temperature, and, after adding ethyl acetate thereto, washed with an aqueous solution, and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was dissolved in dichloromethane (2.0 mL), and trifluoroacetic acid (120 mg) was added dropwise thereto. The reaction solution was stirred for 2 hours at room temperature, then an aqueous sodium bicarbonate solution was added thereto, and the reaction solution was extracted with dichloromethane and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was dissolved in methanol (1 mL) and dichloromethane (1 mL), and after adding N-methylazetidin-3-one (20 mg) and sodium triacetoxyborohydride (115 mg) thereto, the mixture was stirred for 4 hours at room temperature. Dichloromethane was added to the reaction mixture, and the reaction mixture was washed with an aqueous sodium bicarbonate solution and dried with anhydrous magnesium sulfate. The residue obtained by vacuum concentrating the result was purified by silica gel column chromatography (developing solvent: dichloromethane / methanol=9 / 1) to prepare the title compound (11.1 mg, yield: 16.1%).

[0963] 1H NMR (400 MHz, CDCl3) δ 8.19-8.11 (m, 2H), 7.94 (t, 1H), 7.54 (d, 1H), 7.45 (d, 1H), 6.94 (s, 1H), 6.79 (t, 1H), 3.59 (t, 2H), 3.38-3.30 (m, 4H), 3.09-2.96 (m, 3H), 2.88 (s, 3H), 2.75 (s, 3H), 2.56-2.49 (m, 4H), 2.44 (s, 3H), 2.41 (s, 3H). LC / MS (ESI+) m / z=548.2 [M+H]+.

[0964] Example 172. Preparation of 4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(4-(1-isopropylpyrrolidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine

[0965] The title compound was prepared in a yield of 2.4% in the same manner as in Example 156, except that tert-butyl 3-(4-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)piperazin-1-yl)pyrrolidine-1-carboxylate (125 mg) was used instead of tert-butyl 6-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenyl)-2,6-diazaspiro[3.3]heptane-2-carboxylate.

[0966] LC / MS (ESI+) m / z=578.2 [M+H]+.

[0967] Biological Evaluation

[0968] Hereinafter, biological evaluations on specific examples provided in this patent are provided.

[0969] Experimental Example 1: Evaluation on Effect of TREM2 Activation

[0970] The effect of TREM2 activation of the compound was evaluated by measuring the degree of phosphorylation of intracellular spleen tyrosine kinase ("Syk").

[0971] Pharmacological measurements of TREM2 signal transduction via DAP12 were performed using TREM2 and DAP12 overexpressed HEK293 cells ("TREM2 / DAP12-HEK") that are single cell-cloned stable cell lines. In reading the TREM2 signal transduction, Perkin Elmer AlphaScreen / AlphaLISA technology that monitors the phosphorylation level of Syk kinase, a downstream signal transducing mediator, was used. The TREM2 / DAP12-HEK cell line was cultured in DMEM-high glucose (Gibco 11965118 referred to as "HEK culture medium") including 1% penicillin / streptomycin (Gibco 15140122), 0.5 μg / ml puromycin (Gibco A1113803) and 10% fetal bovine serum (Life Technologies 10099). A TREM2 / DAP12-HEK cell suspension was prepared by diluting the cells in the HEK culture medium, and 100 μL volume of the cell suspension was dispensed into a poly-D-lysine-coated 96-well microplate (Corning 3595) so that 40,000 cells are placed per well. The cells placed in the plate were cultured for 20 hours in a humidified cell culture incubator under a condition of 5% CO2at 37°C. After the incubation, the culture medium was removed from all the wells of each plate, and 50 μL of DMEM-high glucose including 0.1% pluronic F-68 polyol (Gibco 24040032) was dispensed. This culture medium was prepared by diluting the test substance or DMSO, a compound diluting solvent, as a negative control group to 0.5%. After the plate was reacted for 45 minutes at 37°C, the culture medium was removed, leaving only the cells. The subsequent processes were performed according to the test method of AlphaScreen (ALSU-PSYK-A10K) product of Perkin Elmer. 50 μL of a cell lysis buffer was dispensed per well, and then a shaking reaction was performed at 500 rpm for 10 minutes at room temperature. The cell sample dissolved in the cell lysis buffer was transferred to a 384-well plate in an amount of 10 μL at a time, and an activation bead mixture was dispensed thereto in an amount of 5 μL at a time. The plate was centrifuged at 1500 rpm for 1 minute, and then reacted for 1 hour at room temperature. After that, a donor bead mixture was made and dispensed thereto in an amount of 5 μL at a time, and the plate was reacted in the same manner. Since the AlphaScreen reagent is sensitive to light, all the reactions were performed with a light source blocked. After the reaction was finished, the alphaScreen signal was measured using an Envision (Perkin Elmer) device with an alphaLISA setting. The signal of each well was converted into a foldchange compared to the DMSO-only treatment group to calculate EC50and Emax. Each foldchange value was entered as a response value and analyzed with a 4-parameter logistic or sigmoidal dose-response model using GraphPad Prism 9 (GraphPad Software, Inc.). The efficacy of the test substance was expressed as EC50corresponding to the test substance concentration capable of activating the phosphorylated Syk AlphaScreen signal to 50% of the maximum response.

[0972] Results presented in the following Table 1 were derived for Examples 1 to 172 using the TREM2 activity evaluation method described above. This evaluation method may be used to, by testing any one of the compounds described herein, evaluate and characterize the ability of the compound to act as an agonist of TREM2.

[0973] The compound designated as "A" exhibited EC50of ≤ 5.0 nM. The compound designated as "B" exhibited EC50of 5.0 nM<EC50≤50 nM.

[0974] Example No.Effect of TREM2 ActivationExample No.Effect of TREM2 Activation1B108A3B109A4B110A5B111B6B112B7B113B10B114B11B115B13B116B17B117B21A118B23B119B24B120B25B121A26B122B27B123A28B124B29B125A30B126B31B127A37B128A38A129B41B130B44A131A45B132A46A133A48B134B52A135B53A136A54A137B55A138B56B139B57A140B58A141B61B142B62B143A63B144B64A145A65B146B66B147A67A148B68A149A69B150B70A151A72B152A73B153B77B154B78B155B79B156B86B157A87B158B89B159A90A160A91B161B92B162B93B163B96B164B98A165A101A166B102A167A103B168B104B169B105A170B106A171B107B172B

[0975] As may be seen from the results of Table 1, the compound according to the present disclosure has very superior TREM2 activity, and therefore, may be useful in preventing and treating various neurodegenerative diseases including Alzheimer's disease, frontotemporal lobar degeneration, Parkinson's disease, Huntington's disease and the like.

[0976] Experimental Example 2: Evaluation of B / P Ratio

[0977] 7- to 8-week old male C57BL / 6 mice (animals produced by Orient Bio were brought in by Hallym Laboratory Animal Research Institute) were quarantined, adapted for 5 to 7 days, and then subjected to an experiment identifying brain uptake. Brain penetration was evaluated by evaluating brain permeability after intravenous administration as an administration path.

[0978] After administering the test substance to each group, each group was anesthetized by inhalation with 2.5% isoflurane (0.25-4%) using RC2 (rodent circuit controller) at 15 minutes and 60 minutes each. It was determined that the mouse was anesthetized when there was no response when lightly touching the tiptoe of the mouse with a forcep, and about 0.5 mL of blood was collected from the heart or postcaval vein of the mouse. The collected blood was placed in a tube for plasma separation treated with lithium heparin as an anticoagulant, and then immediately centrifuged. The plasma for analysis (30 μL) and the remaining plasma were separately placed, and stored frozen until analysis. After the blood was collected, the mouse was naturally bloodletted, the skull was cut open to extract the whole brain and have the weight recorded, and the brain was placed in a tube (7 mL) and stored frozen until analysis. The test compound was dissolved in DMSO (1 or 4 mg / mL) to prepare a working solution. 1.30 μL of the sample was prepared by being diluted with 50% ACN in a 1.5 mL microtube. 150 μL of an internal standard material (5 ng / mL tolterodine in 100% ACN) was added thereto. Vortex and centrifugation were performed at 12,700 rpm for 10 minutes at 4°C. 50 μL of the supernatant was transferred to a 96-well plate. The supernatant was diluted with 50 μL of distilled water and 50 μL of a solution including 0.1% formic acid. The sample was injected into an LC / MS / MS system. Through the LC / MS / MS analysis, the concentrations of the test compound in the brain and the plasma collected at 15 minutes and 60 minutes were identified to measure the brain permeability.

[0979] The compound of the present disclosure may effectively act as a central nervous system drug by exhibiting excellent brain permeability (B / P ratio).

[0980] The present disclosure is applicable to a bicyclic fused-ring (for example, pteridine, pyridopyrimidine, pyridopyrazine, quinazoline, naphthyridine, or quinoxaline) derivative or a pharmaceutically acceptable salt thereof inducing activation of a triggering receptor expressed on myeloid cells 2 (TREM2), a pharmaceutical composition including the same, and a use thereof.

Claims

1.A compound selected from the group consisting of a compound represented by the following Chemical Formula 1, an optical isomer thereof, a solvate thereof, a hydrate thereof, and a pharmaceutically acceptable salt thereof:[Chemical Formula 1]wherein, in Chemical Formula 1,X1, X2, X3and X4are each independently N or CH, provided that at least two of X1to X4are N;R1and R2are each independently hydrogen, halogen, C1-6alkyl or C1-6haloalkyl;A is C6-12aryl or 5- to 12-membered heteroaryl;B is C6-12aryl, 5- to 12-membered heteroaryl or 3- to 12-membered heterocycloalkyl;C is C6-12aryl or 5- to 12-membered heteroaryl;R3are each independently selected from the group consisting of halogen, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6aminoalkyl and C1-6haloalkoxy;R4are each independently selected from the group consisting of halogen, -CN, -NO2and -(C(Rx)2)e-Ry;Rxare each independently hydrogen, halogen, C1-3alkyl or C1-3haloalkyl;e is an integer of 0 to 3;Ryis -Ra, -ORa, -SRa, -N(Ra)2, -CORa, -SO2Ra, -CO2Ra, -OCORa, -CON(Ra)2, -SO2N(Ra)2, -NHCORaor -NHSO2Ra;Raare each independently hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6aminoalkyl, C3-10cycloalkyl or 3- to 12-membered heterocycloalkyl, the cycloalkyl and the heterocycloalkyl are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-6alkyl and C1-6haloalkyl, and when there are a plurality of Ra, these are the same as or different from each other;R5are each independently selected from the group consisting of halogen, -CN, -NO2and -(C(Rx')2)f-Ry';Rx'are each independently hydrogen, halogen, C1-3alkyl or C1-3haloalkyl;f is an integer of 0 to 3;Ry'is -Ra', -ORa', -SRa', -N(Ra')2, -CORa', -SO2Ra', -CO2Ra', -OCORa', -CON(Ra')2, -SO2N(Ra')2, -NHCORa'or -NHSO2Ra';Ra'are each independently hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6aminoalkyl, C3-10cycloalkyl or 3- to 12-membered heterocycloalkyl, the cycloalkyl and the heterocycloalkyl are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-6alkyl and C1-6haloalkyl, and when there are a plurality of Ra', these are the same as or different from each other;when there are two or more R5, the same or different R5optionally bond to each other to form 5- to 12-membered heteroaryl or 3- to 12-membered heterocycloalkyl together with atoms on ring C to which these bond, and herein, the heteroaryl or heterocycloalkyl is optionally substituted with 1 to 3 Rz;Rzare each independently halogen, C1-3alkyl or C1-3haloalkyl;n is an integer of 0 to 4; andm and o are each independently an integer of 0 to 5.2.The compound of claim 1, wherein A is phenyl or 5- or 6-membered heteroaryl.3.The compound of claim 1, which is represented by any one of the following Chemical Formulae 2 to 6:[Chemical Formula 2][Chemical Formula 3][Chemical Formula 4][Chemical Formula 5][Chemical Formula 6]wherein, in Chemical Formulae 2 to 6,p is an integer of 0 to 4;q is an integer of 0 to 3;r is an integer of 0 to 2; andX1to X4, R1, R2, R3, R4, R5, m and o have the same definitions as in claim 1.4.The compound of claim 1, wherein at least three of X1to X4are N.5.The compound of claim 1, wherein R1and R2are each independently C1-6alkyl.6.The compound of claim 1, wherein B is selected from among the following substituents: in the chemical formulae,means a site where a bond is formed;X5to X9are each independently N or C(R4);Y1to Y6are each independently CO, C(R4)2, N(R4), O or S; andR4has the same definition as in claim 1.7.The compound of claim 1, wherein B is selected from among the following substituents: in the chemical formulae,means a site where a bond is formed;s is an integer of 0 to 3;t is an integer of 0 to 2;u is an integer of 0 to 4;v is an integer of 0 to 5; andR4has the same definition as in claim 1.8.The compound of claim 1, whereinR4are each independently -(C(Rx)2)e-Ry;Rxare each independently hydrogen or C1-3alkyl;e is an integer of 0 to 2;Ryis -Ra, -ORa, -SRa, -N(Ra)2, -CORaor -CO2Ra;Raare each independently hydrogen, C1-6alkyl, C3-10cycloalkyl or 3- to 12-membered heterocycloalkyl, the cycloalkyl and the heterocycloalkyl are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-6alkyl and C1-6haloalkyl, and when there are a plurality of Ra, these are the same as or different from each other; andm is an integer of 0 to 3.9.The compound of claim 1, wherein C is selected from among the following substituents:in the chemical formulae,means a site where a bond is formed;X10to X14are each independently N or C(R5);Y7is N(R5), O or S; andR5has the same definition as in claim 1.10.The compound of claim 1, wherein C is selected from among the following substituents:in the chemical formulae,means a site where a bond is formed;w is an integer of 0 to 2;x is an integer of 0 to 5;y is an integer of 0 to 4;z is an integer of 0 to 3; andR5has the same definition as in claim 1.11.The compound of claim 1, whereinR5are each independently selected from the group consisting of halogen, -CN, -NO2and -Ry';Ry'is -Ra', -ORa', -SRa', -N(Ra')2, -CORa', -CO2Ra', -OCORa', -CON(Ra')2, -SO2N(Ra')2or -NHCORa';Ra'are each independently hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C1-6aminoalkyl, C3-10cycloalkyl or 3- to 12-membered heterocycloalkyl, the cycloalkyl and the heterocycloalkyl are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-6alkyl and C1-6haloalkyl, and when there are a plurality of Ra', these are the same as or different from each other;when there are two or more R5, the same or different R5optionally bond to each other to form 5- to 12-membered heteroaryl or 3- to 12-membered heterocycloalkyl together with atoms on ring C to which these bond, and herein, the heteroaryl or heterocycloalkyl is optionally substituted with 1 to 3 Rz;Rzare each independently halogen, C1-3alkyl or C1-3haloalkyl; ando is an integer of 1 to 4.12.A compound selected from the group consisting of a compound selected from the group consisting of the following compounds, an optical isomer thereof, a solvate thereof, a hydrate thereof, and a pharmaceutically acceptable salt thereof:4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2,4-difluoro-5-methylphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(5-chloro-2,4-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(2,4,5-trifluorophenyl)pteridine6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(2,3,4-trifluorophenyl)pteridine4-(2,4-difluoro-3-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(3-chloro-2,4-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2,4-difluoro-3-methylphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2,4-difluoro-3-methoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2-fluoro-4-(methylthio)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2-fluoro-4-methoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridineN-cyclopropyl-4-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluoro-N-methylbenzenesulfonamide4-(2-fluoro-4-isopropoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2,4-difluoro-5-methylphenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(4-chloro-2,3-difluoro-5-methoxyphenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(5-chloro-2,4-difluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(4-chloro-2-fluorophenyl)-2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(4-chloro-2-fluorophenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(2-fluoro-4-methylphenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(2-fluoro-4-methylphenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile4-(2,5-difluoropyridin-4-yl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine6-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine6-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-7-fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one6-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-5-fluoro-2H-benzo[b][1,4]oxazin-3(4H)-one4-(8-fluoroquinolin-7-yl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(4-chloro-2-fluorophenyl)-2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine(3-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-2,6-difluorophenyl)methanol6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(2,3,4-trifluoro-5-methylphenyl)pteridine4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine4-(2-fluoro-3-methoxy-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2,3-difluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(5-chloro-2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine5-(6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-2-(trifluoromethyl)thiazole6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)-4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pteridine3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile4-(6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile4-(6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile4-(4-chloro-2-fluorophenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine2-([3,4-bipyridin]-5-yl)-4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridine4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine4-(2,3-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2,5-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(3,5-difluorophenyl)-6,7-dimethyl-2-(3-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(2,4-difluorophenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(2,4-difluorophenyl)-6,7-dimethyl-2-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)pteridine4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine4-(2,4-difluorophenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine4-(6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridin-4-yl)-3-fluorobenzonitrile4-(2,4-difluorophenyl)-2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(2,4-difluorophenyl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(2,4-difluorophenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)-4-(2,4-difluorophenyl)-6,7-dimethylpteridine4-(2,4-difluorophenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(2,4-difluorophenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine2-([3,4-bipyridin]-5-yl)-4-(2,4-difluorophenyl)-6,7-dimethylpteridine4-(4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorophenyl)morpholine4-(3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)phenyl)morpholine4-(4-(6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridin-4-yl)-3-fluorophenyl)morpholine4-(4-chloro-2-fluorophenyl)-2-(3-(1-isobutyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(4-chloro-2-fluorophenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine2-(3-(1-ethyl-1H-pyrazol-4-yl)phenyl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzamide3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzamide4-fluoro-3-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzamide4-(6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluoro-N,N-dimethylaniline3-fluoro-4-(2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)-N,N-dimethylaniline4-(6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridin-4-yl)-3-fluoro-N,N-dimethylaniline4-(4-chloro-2-fluorophenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine4-(2-fluoro-4-methylphenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(2-fluoro-4-methylphenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine2-([3,4-bipyridin]-5-yl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(2-fluoro-4-(trifluoromethyl)phenyl)-2-(3-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(3-(pyridin-3-yl)phenyl)pteridine2-([3,4-bipyridin]-5-yl)-4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethylpteridine4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine2-([2,4-bipyridin]-4-yl)-4-(2,4-difluorophenyl)-6,7-dimethylpteridine4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-2-(3-(1-isopropyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridine4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-6,7-dimethyl-2-(3-(pyridin-4-yl)phenyl)pteridine4-(6,7-dimethyl-2-(3-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile4-(6,7-dimethyl-2-(3-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile2-([2,4-bipyridin]-4-yl)-4-(2-fluoro-4-methylphenyl)-6,7-dimethylpteridine4-(2-fluoro-4-chlorophenyl)-6,7-dimethyl-2-(3-trifluoromethyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(6,7-dimethyl-2-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile4-(6,7-dimethyl-2-(3-trifluoromethyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile4-(6,7-dimethyl-2-(3-(4-methylpiperazin-1-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile4-(2-fluoro-4-nitrophenyl)-6,7-dimethyl-2-(3-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pteridine4-(6,7-dimethyl-2-(3-methyl-5-(2-methylpyridin-4-yl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile2-([2,4-bipyridin]-4-yl)-4-(2-fluoro-4-chlorophenyl)-6,7-dimethylpteridine4-[4-(difluoromethyl)-2-fluorophenyl]-6,7-dimethyl-2-[3-methyl-5-(pyridin-4-yl)phenyl]pteridine4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(tetrahydrofuran-3-yl)phenyl)pteridine4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-(tetrahydro-2H-pyran-4-yl)phenyl)pteridine4-(2,4-difluorophenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine4-(6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridin-4-yl)-3-fluorobenzonitrile4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine4-(2-fluoro-4-methylphenyl)-6,7-dimethyl-2-(3-methyl-1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine4-(2-fluoro-4-(trifluoromethyl)phenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine4-(2-fluoro-4-chlorophenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine4-(2-fluoro-4-chlorophenyl)-6,7-dimethyl-2-(3-methyl-1-(pyridin-4-yl)-1H-pyrazol-4-yl)pteridine4-(2,4-difluorophenyl)-2-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine4-(2,4-difluorophenyl)-2-(3-fluoro-5-(2-methylpyridin-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine4-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpyrido[2,3-d]pyrimidin-2-yl)-5-fluorophenyl)morpholine4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(2-methylpyridin-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine(4-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-1H-pyrazol-1-yl)(1-methylpiperidin-4-yl)methanone1-(4-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)phenyl)piperazin-1-yl)ethan-1-one3-fluoro-4-(2-(3-fluoro-5-(2-methylpyridin-4-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidin-4-yl)benzonitrile4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpteridine3-fluoro-4-(2-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile3-fluoro-4-(2-(3-fluoro-4-methyl-5-(1-methyl-1H-pyrazol-4-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile4-(4-(difluoromethyl)-2-fluorophenyl)-2-(3-fluoro-5-(4-(2-methoxyethyl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine3-fluoro-4-(2-(3-fluoro-5-(4-isobutyrylpiperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pteridine4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-((1-methylazetidin-3-yl)methyl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine3-fluoro-4-(2-(3-fluoro-5-(4-((1-methylazetidin-3-yl)methyl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile2-(4-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)piperazin-1-yl)-N,N-dimethylethan-1-amine3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylpiperidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitriletert-butyl (3S,5R)-4-(3-(4-(4-cyano-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-3,5-dimethylpiperazine-1-carboxylate4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpyrido[2,3-d]pyrimidine3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile4-(2,4-difluorophenyl)-6,7-dimethyl-2-(4-(pyridin-4-yl)-1H-pyrazol-1-yl)pteridine8-(2,4-difluorophenyl)-2,3-dimethyl-6-(1-(2-methylpyridin-4-yl)-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazine8-(4-chloro-2-fluorophenyl)-6-(3-fluoro-5-(4-methylpiperazin-1-yl)phenyl)-2,3-dimethylpyrido[2,3-b]pyrazine4-(2-(3-(1-acetylpiperidin-3-yl)-5-methylphenyl)-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(2-methyl-6-(4-methylpiperazin-1-yl)pyridin-4-yl)pteridine4-(2-(3-(1-acetylpyrrolidin-3-yl)-5-methylphenyl)-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile1-(5-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)ethan-1-one1-(3-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)piperidin-1-yl)ethan-1-one3-fluoro-4-(2-(3-methyl-5-(4-methylpiperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile2-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)phenyl)hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one4-(2-(3-(1-acetylpyrrolidin-3-yl)-5-fluorophenyl)-6,7-dimethylpteridin-4-yl)-3-fluorobenzonitrile4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(4-methylpiperazin-1-yl)phenyl)pteridine4-(2,4-difluorophenyl)-2-(3-fluoro-5-(1-methylpyrrolidin-3-yl)phenyl)-6,7-dimethylpteridine1-(6-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-2,6-diazaspiro[3.3]heptan-2-yl)-3,3-dimethylbutan-1-one4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(6-isopropyl-2,6-diazaspiro[3.3]heptan-2-yl)phenyl)-6,7-dimethylpteridine4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(1-isopropylpiperidin-4-yl)phenyl)-6,7-dimethylpteridine1-(4-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)piperidin-1-yl)ethan-1-one3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylazetidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile4-(6,7-dimethyl-2-(3-morpholino-5-(trifluoromethyl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(5-isopropyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-6,7-dimethylpteridine4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-isopropylpiperazin-1-yl)phenyl)-6,7-dimethylpteridine1-(3-(4-(2,4-difluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-N,N-dimethylazetidin-3-amine4-(2,4-difluorophenyl)-6,7-dimethyl-2-(4-(2-methylpyridin-4-yl)-1H-pyrazol-1-yl)pteridine3-fluoro-4-(2-(3-fluoro-5-(4-(1-methylpyrrolidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridin-4-yl)benzonitrile4-(6,7-dimethyl-2-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl)pteridin-4-yl)-3-fluorobenzonitrile4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-(1-methylazetidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine1-(3-(4-(4-chloro-2-fluorophenyl)-6,7-dimethylpteridin-2-yl)-5-fluorophenyl)-N,N-dimethylazetidin-3-amine4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-(1-methylpyrrolidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine4-(2,4-difluorophenyl)-2-(3-fluoro-5-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine4-(4-(difluoromethyl)-2-fluorophenyl)-6,7-dimethyl-2-(3-methyl-5-(4-(1-methylazetidin-3-yl)piperazin-1-yl)phenyl)pteridine4-(4-chloro-2-fluorophenyl)-2-(3-fluoro-5-(4-(1-isopropylpyrrolidin-3-yl)piperazin-1-yl)phenyl)-6,7-dimethylpteridine.13.A pharmaceutical composition comprising:the compound of any one of claims 1 to 12; andone or more types of pharmaceutically acceptable carriers.14.A pharmaceutical composition for preventing or treating a neurological disease, the composition comprising the compound of any one of claims 1 to 12 as an active ingredient.15.The pharmaceutical composition of claim 14, wherein the neurological disease is Alzheimer's disease, frontotemporal lobar degeneration, frontotemporal lobar degeneration-like syndrome, Parkinson's disease, Huntington's disease, Nasu-Hakola disease, multiple sclerosis, Guillain-Barr syndrome, chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis (ALS), rheumatoid arthritis, prion disease, or stroke.

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