4-(imidazo[1,2-a]pyridin-3-yl)-pyrimidine derivatives

Abstract

To provide compounds that can be employed for the treatment of cancer.SOLUTION: There are provided compounds represented by Formula I. In the formula, R1 denotes H, Hal, CF3, NO or the like. R2 denotes H or CH3. R3 denotes H or A. A denotes unbranched / branched, unsubstituted / substituted alkyl with 1 to 10 C-atoms. V denotes H or Hal. X denotes O or N(R3). Y denotes phenylene, pyridin-diyl, thiophen-diyl, 1,3-thiazol-diyl or pyrazol-diyl, and Z denotes CON(R3)2, phenyl, or the like.SELECTED DRAWING: None

Description

[Technical Field]

[0001] Background of the Invention The present invention had the object of finding new compounds with valuable properties, in particular new compounds that can be used for the preparation of medicines.

[0002] The present invention relates to 4-(imidazo[1,2-a]pyridin-3-yl)-pyrimidine derivatives that inhibit c-KIT across a wide range of c-KIT kinase mutations and secondary mutations (secondary resistance mutation V654A in exon 13) that can occur in patients with GIST (gastrointestinal stromal tumor). The compounds of the present invention are therefore useful for treating diseases such as cancer. The present invention also provides methods for preparing these compounds, pharmaceutical compositions containing these compounds, compounds for use in treating diseases, and methods for treating diseases using pharmaceutical compositions containing these compounds. Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal (GI) tract.

[0003] c-KIT is a type III receptor tyrosine kinase that plays an important role in the occurrence of cancer. Mutant forms of the receptor tyrosine kinase c-KIT are drivers of several cancers, such as GIST, SM (systemic mastocytosis), some types of AML, and melanoma, and are therefore attractive targets for therapy. Gain-of-function mutations in KIT play an important role in the pathogenesis of gastrointestinal tumors (GIST).

[0004] GISTs are defined as mesenchymal spindle cell or epithelioid neoplasms that are c-KIT (CD117, stem cell factor receptor) positive. GISTs commonly harbor primary activating mutations in the KIT gene (90%), which lead to ligand-independent activation of the receptor tyrosine kinase c-KIT, making the tumor dependent on oncogenic KIT activity.

[0005] Although benefit is seen from the use of inhibitors of KIT kinase activity (e.g., imatinib), particularly in GIST, primary resistance occurs in association with certain oncogenic mutations. Furthermore, resistance frequently arises due to secondary mutations (L.K. Ashman & R. Griffith (2013) Expert Opinion on Investigational Drugs, 22:1, 103-115). Treatment of GIST with primary mutations with imatinib has an initial response rate of ~70%, but acquired resistance has been reported to develop in 40-50% of cases within an average of 2 years. The secondary mutation V654A in exon 13 is the most frequent resistance mutation after imatinib treatment.

[0006] L C Chen et al. describe "A Missense Mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors" in Cancer Res. 2004;64:5913-5919. K G Roberts et al. describe "Resistance to c-KIT kinase inhibitors conferred by V654A mutation" in Mol. Cancer Ther. 2007;6:1159-1166. There is a large unmet medical need for the development of safe and specific inhibitors for the KIT V654A resistance mutation.

[0007] The compounds according to the invention and their salts have been found to possess highly valuable pharmacological properties whilst being well tolerated. The present invention specifically relates to compounds of formula I that inhibit c-KIT kinase, preferably the V654A mutant of c-KIT kinase.

[0008] Furthermore, the compound of formula I inhibits PDGFRα(V651D). Gain-of-function mutations of PDGFRα appear to play an important role in the development of GISTs lacking KIT mutations (S. Hirota et al., Gastroenterology 2003;125:660-667).

[0009] The host or patient may belong to any mammalian species, for example, primates, particularly humans; rodents, including mice, rats, and hamsters; rabbits; horses, cows, dogs, cats, etc. Animal models are objects for experimental investigation and provide models for the treatment of human diseases.

[0010] The sensitivity of specific cells to treatment with the compounds of the present invention can be determined by in vitro testing. Typically, cell cultures are combined with various concentrations of the compounds of the present invention for a period of time (usually between about 1 hour and 1 week) sufficient for the active agent, such as anti-IgM, to induce a cellular response, such as the expression of surface markers. In vitro testing can be performed using cells cultured from blood or biopsy samples. The amount of expressed surface markers is assessed by flow cytometry using specific antibodies that recognize the markers.

[0011] Doses will vary depending on the particular compound used, the particular disease, the patient's condition, etc. A therapeutic dose is typically sufficient to substantially reduce the undesirable cell population in the target tissue while maintaining patient viability. Treatment is generally continued until a substantial reduction has occurred, e.g., at least about a 50% reduction in cell burden, and may be continued until the undesirable cells are essentially undetectable in the body.

[0012] prior art WO 2010 / 009155 discloses other fused heterocyclic compounds as inhibitors of histone deacetylases and / or cyclin-dependent kinases. WO 2011 / 076419 discloses imidazopyridines as inhibitors of JAK kinases. Summary of the Invention

[0013] SUMMARY OF THE INVENTION The present invention relates to a compound of formula I [ka] During the ceremony R 1 H, Hal, CF3, NO2, A, [C(R 3 )2] n N(R 3 )2, [C(R 3 )2] n Het 1 , OR 3 , O[C(R 3 )2] n N(R 3 )2, O[C(R 3 )2] n S(O) m R 3 , O[C(R 3 )2] n COOR 3 , O[C(R 3 )2] n COON(R 3 )2, O[C(R 3 )2] n Het 1 , O[C(R 3 )2] n N(R 3 )Het 1 , O[C(R 3 )2] n Ph, or O[C(R 3 )2] n Cyc indicates (denotes), R 2 indicates H or CH3, R 3 indicates H or A, V represents H or Hal; X is O or N(R 3 ) and Y represents phenylene, pyridine-diyl, thiophene-diyl, 1,3-thiazole-diyl, or pyrazole-diyl, each of which is unsubstituted or mono-, di-, or tri-substituted by Hal and / or A; Z is CON(R 3 )2, Phenyl, Het 4 , or -OA, Het 1 denotes a 4-, 5-, 6-, or 7-membered monocyclic aromatic, unsaturated, or saturated heterocycle having 1, 2, 3, or 4 N, O, and / or S atoms, which may be unsubstituted or substituted with A, Hal, CN, OR 3 , [C(R 3 )2] n N(R 3 )2, [C(R 3 )2] n SO2R 3 , Het 2 , oxetanyl, =NR 3 and / or may be mono-, di- or trisubstituted by =O, wherein the N atom is optionally oxidized; Or, Het 1 denotes a 6-, 7-, 8-, 9-, or 10-membered bicyclic or spirocyclic aromatic, unsaturated, or saturated heterocycle having 1, 2, 3, or 4 N, O, and / or S atoms, which may be unsubstituted or substituted with A, Hal, CN, OR 3 , [C(R 3 )2] n N(R 3 )2, [C(R 3 )2] n SO2R 3 , Het 2 , oxetanyl, =NR 3 and / or may be mono-, di- or trisubstituted by =O, wherein the N atom is optionally oxidized; Het 2represents a 5-6 membered monocyclic aromatic or unsaturated heterocycle having 1, 2, 3 or 4 N, O and / or S atoms, which may be unsubstituted or mono- or disubstituted by A and / or Hal; Or, Het 2 represents a 7-, 8-, 9- or 10-membered bicyclic aromatic or unsaturated heterocycle having 1, 2, 3 or 4 N, O and / or S atoms, which may be unsubstituted or mono- or disubstituted by A and / or Hal; Het 3 denotes a 4-, 5-, 6-, or 7-membered monocyclic saturated heterocycle having 1, 2, 3, or 4 N and / or O atoms, which may be unsubstituted or may be substituted with A, Hal, OR 3 and / or may be mono- or disubstituted by =O, Het 4 denotes a 4-, 5-, 6-, or 7-membered monocyclic aromatic, unsaturated, or saturated heterocycle having 1, 2, 3, or 4 N and / or O atoms, which may be unsubstituted or may be substituted with A, Hal, OR 3 , [C(R 3 )2] n Het 3 , -N(R 3 )2, and / or ═O, Or, Het 4 denotes a 6-, 7-, 8-, 9-, or 10-membered bicyclic aromatic, unsaturated, or saturated heterocycle having 1, 2, 3, or 4 N and / or O atoms, which may be unsubstituted or may be substituted with A, Hal, OR 3 , [C(R 3 )2] n Het 3 and / or may be mono-, di-, or trisubstituted by ═O; A denotes unbranched or branched alkyl with 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 C atoms, in which 1, 2, or 3 non-adjacent CH and / or CH groups may be replaced by an O atom or NH, and in which 1, 2, 3, 4, 5, 6, or 7 H atoms are replaced by R 5 may be replaced by Alternatively, A is (CH2) n Cyc indicates Cyc denotes a cyclic alkyl having 3, 4, 5, 6 or 7 C atoms, R 5 represents F, Cl, CN, or OH, Ph represents phenyl, which may be unsubstituted or may be A, OR 3 and / or may be mono-, di- or trisubstituted by Hal, Hal represents F, Cl, Br, or I; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; and / or a pharmaceutically acceptable salt, tautomer, and / or stereoisomer thereof.

[0014] In one aspect, the present invention provides a compound of formula I [ka] During the ceremony R 1 H, Hal, CF3, NO2, A, [C(R 3 )2] n N(R 3 )2, [C(R 3 )2] n Het 1 , OR 3 , O[C(R 3 )2] n N(R 3 )2, O[C(R 3 )2] n S(O) m R 3 , O[C(R3 )2] n COOR 3 , O[C(R 3 )2] n COON(R 3 )2, O[C(R 3 )2] n Het 1 , O[C(R 3 )2] n Ph, or O[C(R 3 )2] n Cyc indicates R 2 indicates H or CH3, R 3 indicates H or A, V represents H or Hal; X is O or N(R 3 ) and Y represents phenylene, pyridine-diyl, thiophene-diyl, 1,3-thiazole-diyl, or pyrazole-diyl, each of which is unsubstituted or mono-, di-, or tri-substituted by Hal and / or A; Z is CON(R 3 )2, phenyl, or Het 4 indicates, Het 1 denotes a 4-7 membered monocyclic aromatic, unsaturated or saturated heterocycle having 1-4 N, O and / or S atoms, which may be unsubstituted or substituted with A, Hal, CN, OR 3 , [C(R 3 )2] n N(R 3 )2, [C(R 3 )2] n SO2R 3 , Het 2 , oxetanyl, =NR 3 and / or may be mono-, di- or trisubstituted by =O, wherein the N atom is optionally oxidized; Or, Het 1denotes a 7-10 membered bicyclic or spirocyclic aromatic, unsaturated or saturated heterocycle having 1-4 N, O and / or S atoms, which may be unsubstituted or substituted with A, Hal, CN, OR 3 , [C(R 3 )2] n N(R 3 )2, [C(R 3 )2] n SO2R 3 , Het 2 , oxetanyl, =NR 3 and / or may be mono-, di- or trisubstituted by =O, wherein the N atom is optionally oxidized; Het 2 represents a 5-6 membered monocyclic aromatic or unsaturated heterocycle having 1-4 N, O and / or S atoms, which may be unsubstituted or mono- or disubstituted by A and / or Hal; Or, Het 2 represents a 7-10 membered bicyclic aromatic or unsaturated heterocycle having 1-4 N, O and / or S atoms, which may be unsubstituted or mono- or disubstituted by A and / or Hal; Het 3 denotes a 4-7 membered monocyclic saturated heterocycle having 1-4 N and / or O atoms, which may be unsubstituted or may be substituted with A, Hal, OR 3 and / or may be mono- or disubstituted by =O, Het 4 denotes a 4-7 membered monocyclic aromatic, unsaturated or saturated heterocycle having 1-4 N and / or O atoms, which may be unsubstituted or may be substituted with A, Hal, OR 3 , [C(R 3 )2] n Het 3 and / or may be mono-, di-, or trisubstituted by ═O; Or, Het 4denotes a 6-10 membered bicyclic aromatic, unsaturated or saturated heterocycle having 1-4 N and / or O atoms, which may be unsubstituted or may be substituted with A, Hal, OR 3 , [C(R 3 )2] n Het 3 and / or may be mono-, di-, or trisubstituted by ═O; A represents an unbranched or branched alkyl having 1 to 10 C atoms, wherein 1 to 3 non-adjacent CH and / or CH groups may be replaced by O atoms or NH, and wherein 1 to 7 H atoms are R 5 may be replaced by Alternatively, A is (CH2) n Cyc indicates Cyc represents a cyclic alkyl having 3 to 7 carbon atoms, R 5 represents F, Cl, CN, or OH, Ph represents phenyl, which may be unsubstituted or may be A, OR 3 and / or may be mono-, di- or trisubstituted by Hal, Hal represents F, Cl, Br, or I; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; and their pharmaceutically acceptable salts, tautomers, and stereoisomers, and mixtures thereof in any proportion.

[0015] The invention also covers the optically active forms (stereoisomers), enantiomers, racemates (racemic mixtures), diastereomers, tautomers, and solvates of these compounds, as well as processes for making them. Any reference to a compound or a salt thereof shall be understood to cover solvates thereof.

[0016] The term solvates of the compounds is understood to mean adducts of inert solvent molecules onto the compounds, which form due to their mutual attractive force. Solvates are, for example, hydrates, including mono- or dihydrates, or alkoxides. It will be understood that the present invention is also intended to cover solvates of the salts.

[0017] The present invention also relates to mixtures of compounds of formula I, for example mixtures of two diastereomers, for example in ratios of 1:1, 1:2, 1:3, 1:4, 1:5, 1:10, 1:100 or 1:1000. These are particularly preferably mixtures of stereoisomeric compounds.

[0018] "Tautomers" refer to isomeric forms of a compound that exist in equilibrium with each other. The concentrations of isomeric forms may differ depending on the environment in which the compound is found, for example, whether the compound is a solid or in an organic or aqueous solution.

[0019] The present invention relates to compounds of formula I, and their pharmaceutically acceptable salts, tautomers, and stereoisomers, and to processes for the preparation of compounds of formula I, and their pharmaceutically acceptable salts, tautomers, and stereoisomers, characterized in that: a) Formula I (wherein X is N(R 3 ) for the preparation of a compound of formula II [ka] (R in the formula 1 and V have the meanings given above and below in any one of claims 1 to 8) of the compound of formula III H2N-(CHR 2 )-YZ III (R in the formula 2 , Y, and Z have the meanings given above and below in any one of claims 1 to 8), or or b) for the preparation of compounds of formula I, [ka] (R in the formula 1 and V have the meanings given above and below in any one of claims 1 to 8), [ka] (R in the formula 2 , V, X, Y and Z have the meanings given above and below in any of claims 1 to 8), or or c) for the preparation of compounds of formula I, 1 represents F), to obtain a compound represented by another formula (wherein R 1 is O[C(R 3 )2] n N(R 3 )2, O[C(R 3 )2] n N(R 3 )Het 1 , or O[C(R 3 )2] n Het 1 where R 3 and Het 1 have the meanings given above and below in any one of claims 1 to 8), or or d) a compound of formula I, wherein Z is Het 4 For the preparation of a compound of formula VI [ka] (R in the formula 1 , R 2 , V, X and Y have the meanings given above and below in any one of claims 1 to 8) is a compound of formula VII HZ VII (wherein Z is Het 4or and / or A base or acid of formula I, ie a compound of formula I (which may react as a base or an acid), is converted into one of its salts.

[0020] For example, R 3 For all radicals that occur more than once, such as , their meanings are independent of each other. 1 , R 2 , V, X, Y, and Z, unless expressly specified otherwise, have the meanings indicated for Formula I. The same applies to the variables n and m, and radicals that may be designated according to the aforementioned meanings.

[0021] The exemplary embodiments of radicals and variables disclosed herein associated with the compounds of the invention are equally applicable to the above processes for preparing them.

[0022] "A" represents an alkyl group that is unbranched or branched and has 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 C atoms. As noted above, 1 to 3 non-adjacent CH and / or CH groups may be replaced by O atoms or NH, and 1 to 7 H atoms may be replaced by R 5 or "A" may be replaced by (CH) n"A" represents Cyc. Illustratively, "A" represents methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl, and also pentyl, 1-, 2- or 3-methylbutyl, 1,1-, 1,2- or 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-, 2-, 3- or 4-methylpentyl, 1,1-, 1,2-, 1,3-, 2,2-, 2,3- or 3,3-dimethylbutyl, 1- or 2-ethylbutyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, 1,1,2- or 1,2,2-trimethylpropyl, and even more preferably trifluoromethyl.

[0023] In preferred embodiments, "A" denotes alkyl having 1, 2, 3, 4, 5, or 6 C atoms, which may be unsubstituted or substituted, and is preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, trifluoromethyl, pentafluoroethyl, or 1,1,1-trifluoroethyl. Cyc preferably denotes cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. In other preferred embodiments, "A" denotes CHOCH, CHCHOH, OCHCHOH, OCHCHOCH, CHCHOCH, OCH(CHOCH), or OCHC(CH)OH.

[0024] In an exemplary embodiment: R 1 is preferably H, F, OCH2CH2OCH3, OCH3, CF3, O[C(R 3 )2] n N(R 3 )2, O[C(R 3 )2] n Het 1 , O[C(R 3 )2] n N(R 3 )Het 1 , OCH(CH2OCH3)2, O[C(R 3 )2] nCyc, OCH2C(CH3)2OH, CH3, O[C(R 3 )2] n Ph, NO2, Cl, OH, OCH2C(CH3)2NH2, NHCH2C(CH3)2OH, [C(R 3 )2] n Het 1 , OCH2CH2OH, OCH2CH2CH2OH, O[C(R 3 )2] n S(O) m R 3 , or OCH2CH2OCH2CH2OH. R 3 preferably denotes H or A, most preferably H or CH3. V preferably denotes H or F, most preferably H. X preferably represents O or NH, most preferably NH. Y preferably denotes 1,4-phenylene, 1,3-phenylene, pyridine-3,6-diyl, 4-methyl-pyridine-3,6-diyl, 4-fluoro-pyridine-3,6-diyl, 3-fluoro-1,4-phenylene, thiophene-2,5-diyl or pyridine-2,5-diyl.

[0025] Bicyclic compounds also include spiro compounds.

[0026] Regardless of further substitutions, Het 1is, for example, 2- or 3-furyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2, 4- or 5-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, even more preferably 1,2,3-triazol-1-, -4- or -5-yl, 1,2,4-triazolyl, 1-, 2-, 3-, 4-, 5-indolyl, 1- or 5-tetrazolyl, 1,2,3-oxadiazol-4- or -5-yl, 1,2,4-oxadiazol-3- or -5-yl, 1,3,4-thiadiazol-2- or -5-yl, 1,2,4-thiadiazol-3- or -5-yl, 1,2,3-thiadiazol-4- or -5-yl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 4- or 5-isoindolyl, indazolyl, 1-, 2-, 4- or is 5-benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-benzopyrazolyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 3-, 4-, 5-, 6- or 7-benzisoxazolyl, 2-, 4-, 5-, 6- or 7-benzothiazolyl, 2-, 4-, 5-, 6- or 7-benzisothiazolyl, 4-, 5-, 6- or 7-benz-2,1,3-oxadiazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 3-, 4- , 5-, 6-, 7- or 8-cinnolinyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 5- or 6-quinoxalinyl, 2-, 3-, 5-, 6-, 7- or 8-2H-benzo-1,4-oxazinyl, pyrrolopyridinyl, purinyl, more preferably 1,3-benzodioxol-5-yl, 1,4-benzodioxan-6-yl, 2,1,3-benzothiadiazol-4- or -5-yl, 2,1,3-benzoxadiazol-5-yl, azabicyclo[3.2.1]-octyl or dibenzofuranyl.The heterocyclic radical may also be partially or fully hydrogenated, regardless of further substitution, thus Het. 1is also, for example, 2,3-dihydro-2-, -3-, -4- or -5-furyl, 2,5-dihydro-2-, -3-, -4- or -5-furyl, tetrahydro-2- or -3-furyl, 1,3-dioxolan-4-yl, tetrahydro-2- or -3-thienyl, 2,3-dihydro-1-, -2-, -3-, -4- or -5-pyrrolyl, 2,5-dihydro-1- , -2-, -3-, -4- or -5-pyrrolyl, 1-, 2- or 3-pyrrolidinyl, tetrahydro-1-, -2- or -4-imidazolyl, 2,3-dihydro-1-, -2-, -3-, -4- or -5-pyrazolyl, tetrahydro-1-, -3- or -4-pyrazolyl, 1,4-dihydro-1-, -2-, -3- or -4-pyridyl, 1,2,3,4-tetrahydro- tetrahydro-1-, -2-, -3-, -4-, -5- or -6-pyridyl, 1-, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-morpholinyl, tetrahydro-2-, -3- or -4-pyranyl, 1,4-dioxanyl, 1,3-dioxan-2-, -4- or -5-yl, hexahydro-1-, -3- or -4-pyridazinyl, hexahydro -1-, -2-, -4- or -5-pyrimidinyl, 1-, 2- or 3-piperazinyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or -8-quinolyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or -8-isoquinolyl, 2-, 3-, 5-, 6-, 7- or 8-isoquinolyl Also 3,4-dihydro-2H-benzo-1,4-oxazinyl, further 2,3-methylenedioxyphenyl, 3,4-methylenedioxyphenyl, 2,3-ethylenedioxyphenyl, 3,4-ethylenedioxyphenyl, 3,4-(difluoromethylenedioxy)phenyl, 2,3-dihydrobenzofuran-5- or 6-yl, 2,3-(2-oxomethylenedioxy)phenyl, or also 3,4-dihydro-2H-1,5-benzodioxepin-6- or -7-yl, further also 2,3-dihydrobenzofuranyl, 2,3-dihydro-2-oxofuranyl, 3,4-dihydro-2-oxo-1H-quinazolinyl, 2,3-dihydrobenzoxazolyl, 2-oxo-2,It may also represent 3-dihydrobenzoxazolyl, 2,3-dihydrobenzimidazolyl, 1,3-dihydroindole, 2-oxo-1,3-dihydroindole, or 2-oxo-2,3-dihydrobenzimidazolyl.

[0027] Het 1 is preferably morpholinyl, tetrahydro-pyran-4-yl, tetrahydro-furan-3-yl, pyrrolidinyl, piperazinyl, piperidinyl, 6-oxa-3-azabicyclo[3.1.1]heptan-3-yl, pyridinyl, pyridazinyl, 2-oxa-6-azaspiro[3.3]heptan-6-yl, imidazolyl, azetidinyl, 3-aza-bicyclo[3.1.0]hexane- 3-yl, 1 lambda 6-thiomorpholinyl, 1l4-thiomorpholinyl, 1,3-dihydro-pyrrolo[3,4-c]pyridinyl, 3,8-diaza-bicyclo[3.2.1]octan-8-yl, 2l4-thia-5-aza-bicyclo[2.2.1]heptan-5-yl, [1,4]oxazepanyl, hexahydro-pyrazino[2,1-c][1,4]oxazin-8-yl, 5,6-dihydro -8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl, 5,6-dihydro-8H-[1,2,4]triazolo[1,5-a]pyrazin-7-yl, 6-oxa-1-aza-spiro[3.3]heptan-1-yl, hexahydro-furo[3,2-b]pyridin-4-yl, hexahydro-pyrano[3,4-b][1,4]oxazin-1-yl, pyrazolyl, 1,4-diaza -bicyclo[3.2.1]octan-4-yl, 1,2,4-oxadiazolyl, 6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl, 6,7-dihydro-4H-[1,2,3]triazolo[1,5-a]pyrazin-5-yl, 3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-2-yl, 1,4-diazepanyl, triazolyl, or oxetanyl, Each of these may be unsubstituted or may be A, Hal, CN, OR 3 , [C(R 3 )2] n N(R 3 )2, [C(R 3 )2] nSO2R 3 , Het 2 , oxetanyl, =NR 3 and / or may be mono-, di-, or trisubstituted by ═O; In addition, the N atom may be oxidized.

[0028] Regardless of further substitutions, Het 2is, for example, 2- or 3-furyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2, 4- or 5-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, even more preferably 1,2,3-triazol-1-, -4- or -5-yl, 1,2,4-triazol-1-, -4- or -5-yl, 1-, 3- or 5-thiadiazolyl, 1- or 5-tetrazolyl, 1,2,3-oxadiazol-4- or -5-yl, 1,2,4-oxadiazol-3- or -5-yl, 1,3,4-thiadiazol-2- or -5-yl, 1,2,4-thiadiazol-3- or -5-yl, 1,2,3-thiadiazol-4- or -5-yl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 4- or 5-isoindolyl, indazolyl, 1-, 2-, 4- or 5- -benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-benzopyrazolyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 3-, 4-, 5-, 6- or 7-benzisoxazolyl, 2-, 4-, 5-, 6- or 7-benzothiazolyl, 2-, 4-, 5-, 6- or 7-benzisothiazolyl, 4-, 5-, 6- or 7-benz-2,1,3-oxadiazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 3-, 4- or 5- , 6-, 7- or 8-cinnolinyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 5- or 6-quinoxalinyl, 2-, 3-, 5-, 6-, 7- or 8-2H-benzo-1,4-oxazinyl, pyrrolopyridinyl, purinyl, more preferably 1,3-benzodioxol-5-yl, 1,4-benzodioxan-6-yl, 2,1,3-benzothiadiazol-4- or -5-yl, 2,1,3-benzoxadiazol-5-yl, azabicyclo[3.2.1]-octyl or dibenzofuranyl.

[0029] Het 2 preferably denotes furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, triazolyl, tetrazolyl, oxadiazolyl, pyridazinyl, pyrazinyl, 1,3-benzodiazolyl, 1,3-benzodioxolyl, indolyl, isoindolyl, or indazolyl, each of which may be unsubstituted or mono- or disubstituted by A and / or Hal.

[0030] Het 3 preferably denotes morpholinyl, pyrrolidinyl, piperidinyl, oxetanyl, or azetidinyl, each of which may be unsubstituted or may be substituted with A, Hal, OR 3 and / or ═O.

[0031] Regardless of further substitutions, Het 4is, for example, 2- or 3-furyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2, 4- or 5-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, even more preferably 1,2,3-triazol-1-, -4- or -5-yl, 1,2,4-triazol-1-, -4- or -5-yl, 1-, 3- or 5-thiadiazolyl, 1- or 5-tetrazolyl, 1,2,3-oxadiazol-4- or -5-yl, 1,2,4-oxadiazol-3- or -5-yl, 1,3,4-thiadiazol-2- or -5-yl, 1,2,4-thiadiazol-3- or -5-yl, 1,2,3-thiadiazol-4- or -5-yl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 4- or 5-isoindolyl, indazolyl, 1-, 2-, 4- or 5- -benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-benzopyrazolyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 3-, 4-, 5-, 6- or 7-benzisoxazolyl, 2-, 4-, 5-, 6- or 7-benzothiazolyl, 2-, 4-, 5-, 6- or 7-benzisothiazolyl, 4-, 5-, 6- or 7-benz-2,1,3-oxadiazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 3-, 4- or 5- , 6-, 7- or 8-cinnolinyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 5- or 6-quinoxalinyl, 2-, 3-, 5-, 6-, 7- or 8-2H-benzo-1,4-oxazinyl, pyrrolopyridinyl, purinyl, more preferably 1,3-benzodioxol-5-yl, 1,4-benzodioxan-6-yl, 2,1,3-benzothiadiazol-4- or -5-yl, 2,1,3-benzoxadiazol-5-yl, azabicyclo[3.2.1]-octyl or dibenzofuranyl.The heterocyclic radical may also be partially or fully hydrogenated, regardless of further substitution, thus Het. 4is also, for example, 2,3-dihydro-2-, -3-, -4- or -5-furyl, 2,5-dihydro-2-, -3-, -4- or -5-furyl, tetrahydro-2- or -3-furyl, 1,3-dioxolan-4-yl, tetrahydro-2- or -3-thienyl, 2,3-dihydro-1-, -2-, -3-, -4- or -5-pyrrolyl, 2,5-dihydro-1- , -2-, -3-, -4- or -5-pyrrolyl, 1-, 2- or 3-pyrrolidinyl, tetrahydro-1-, -2- or -4-imidazolyl, 2,3-dihydro-1-, -2-, -3-, -4- or -5-pyrazolyl, tetrahydro-1-, -3- or -4-pyrazolyl, 1,4-dihydro-1-, -2-, -3- or -4-pyridyl, 1,2,3,4-tetrahydro- tetrahydro-1-, -2-, -3-, -4-, -5- or -6-pyridyl, 1-, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-morpholinyl, tetrahydro-2-, -3- or -4-pyranyl, 1,4-dioxanyl, 1,3-dioxan-2-, -4- or -5-yl, hexahydro-1-, -3- or -4-pyridazinyl, hexahydro -1-, -2-, -4- or -5-pyrimidinyl, 1-, 2- or 3-piperazinyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or -8-quinolyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or -8-isoquinolyl, 2-, 3-, 5-, 6-, 7- or 8-isoquinolyl Also 3,4-dihydro-2H-benzo-1,4-oxazinyl, further 2,3-methylenedioxyphenyl, 3,4-methylenedioxyphenyl, 2,3-ethylenedioxyphenyl, 3,4-ethylenedioxyphenyl, 3,4-(difluoromethylenedioxy)phenyl, 2,3-dihydrobenzofuran-5- or 6-yl, 2,3-(2-oxomethylenedioxy)phenyl, or also 3,4-dihydro-2H-1,5-benzodioxepin-6- or -7-yl, further also 2,3-dihydrobenzofuranyl, 2,3-dihydro-2-oxofuranyl, 3,4-dihydro-2-oxo-1H-quinazolinyl, 2,3-dihydrobenzoxazolyl, 2-oxo-2,It may also represent 3-dihydrobenzoxazolyl, 2,3-dihydrobenzimidazolyl, 1,3-dihydroindole, 2-oxo-1,3-dihydroindole, or 2-oxo-2,3-dihydrobenzimidazolyl.

[0032] Het 4 preferably represents pyrrolidinyl, 3-aza-bicyclo[3.1.0]hexan-3-yl, pyrazolyl, pyridinyl, imidazolyl, 4,5-dihydro-1H-imidazolyl, triazolyl, 4H,5H,6H-pyrrolo[1,2-b]pyrazol-3-yl, oxadiazolyl, 1,3-benzodiazolyl, pyrimidinyl, tetrazolyl, 8-oxa-3-aza-bicyclo[3.2.1]octan-3-yl, pyridazinyl, oxazolyl, isoxazolyl, each of which may be unsubstituted or may be represented by A, Hal, OR 3 , [C(R 3 )2] n Het 3 , -N(R 3 )2, and / or ═O.

[0033] As already mentioned above, throughout the present invention, all radicals occurring more than once may be identical or different, ie independent of one another. The compounds of formula I may contain one or more chiral centers and therefore may exist in various stereoisomeric forms, and formula I encompasses all such forms.

[0034] Consequently, the present invention relates in particular to compounds of formula I in which at least one of the radicals has one of the preferred meanings indicated above. Some preferred groups of compounds may be represented by the following sub-formulae Ia to Iw, which are compatible with formula I, in which the radicals not specified in more detail have the meanings indicated for formula I, but in which:

[0035] In Ia, R 1are H, F, OCH2CH2OCH3, OCH3, CF3, O[C(R 3 )2] n N(R 3 )2, O[C(R 3 )2] n Het 1 , O[C(R 3 )2] n N(R 3 )Het 1 , OCH(CH2OCH3)2, O[C(R 3 )2] n Cyc, OCH2C(CH3)2OH, CH3, O[C(R 3 )2] n Ph, NO2, Cl, OH, OCH2C(CH3)2NH2, NHCH2C(CH3)2OH, [C(R 3 )2] n Het 1 , OCH2CH2OH, OCH2CH2CH2OH, O[C(R 3 )2] n S(O) m R 3 , or OCH2CH2OCH2CH2OH, In Ib, R 3 indicates H or A; In Ic, R 3 indicates H or CH3; In Id, X represents O or NH; In Ie, Y represents 1,4-phenylene, 1,3-phenylene, pyridine-3,6-diyl, 4-methyl-pyridine-3,6-diyl, 4-fluoro-pyridine-3,6-diyl, 3-fluoro-1,4-phenylene, thiophene-2,5-diyl, or pyridine-2,5-diyl;

[0036] In If, Het 1are morpholinyl, tetrahydro-pyran-4-yl, tetrahydro-furan-3-yl, pyrrolidinyl, piperazinyl, piperidinyl, 6-oxa-3-azabicyclo[3.1.1]heptan-3-yl, pyridinyl, pyridazinyl, 2-oxa-6-azaspiro[3.3]heptan-6-yl, imidazolyl, azetidinyl, 3-aza-bicyclo[3.1.0]hexan-3-yl, 1 lambda 6-thiazolinyl, 2-oxa-6-azaspiro[3.3]heptan-6-yl, 2-oxa-6-azaspiro[3.1.0]hex ... omorpholinyl, 1l4-thiomorpholinyl, 1,3-dihydro-pyrrolo[3,4-c]pyridinyl, 3,8-diaza-bicyclo[3.2.1]octan-8-yl, 2l4-thia-5-aza-bicyclo[2.2.1]heptan-5-yl, [1,4]oxazepanyl, hexahydro-pyrazino[2,1-c][1,4]oxazin-8-yl, 5,6-dihydro-8H-[1,2,4]triazolo[4, 3-a]pyrazin-7-yl, 5,6-dihydro-8H-[1,2,4]triazolo[1,5-a]pyrazin-7-yl, 6-oxa-1-aza-spiro[3.3]heptan-1-yl, hexahydro-furo[3,2-b]pyridin-4-yl, hexahydro-pyrano[3,4-b][1,4]oxazin-1-yl, pyrazolyl, 1,4-diaza-bicyclo[3.2.1]octan-4-yl, 1,2 ,4-oxadiazolyl, 6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl, 6,7-dihydro-4H-[1,2,3]triazolo[1,5-a]pyrazin-5-yl, 3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-2-yl, 1,4-diazepanyl, triazolyl, or oxetanyl, each of which may be unsubstituted or may be selected from the group consisting of A, Hal, CN, OR 3 , [C(R 3 )2] n N(R 3 )2, [C(R 3 )2] n SO2R 3 , Het 2 , oxetanyl, =NR 3 and / or may be mono-, di-, or trisubstituted by =O, and wherein the N atom is optionally oxidized;

[0037] In Ig, Het 2denotes furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, triazolyl, tetrazolyl, oxadiazolyl, pyridazinyl, pyrazinyl, 1,3-benzodiazolyl, 1,3-benzodioxolyl, indolyl, isoindolyl, or indazolyl, each of which may be unsubstituted or mono- or disubstituted by A and / or Hal;

[0038] In Ih, Het 3 denotes morpholinyl, pyrrolidinyl, piperidinyl, oxetanyl, or azetidinyl, each of which may be unsubstituted or may be substituted with A, Hal, OR 3 and / or may be mono- or disubstituted by =O; In Ii, Het 4 represents pyrrolidinyl, 3-aza-bicyclo[3.1.0]hexan-3-yl, pyrazolyl, pyridinyl, imidazolyl, 4,5-dihydro-1H-imidazolyl, triazolyl, 4H,5H,6H-pyrrolo[1,2-b]pyrazol-3-yl, oxadiazolyl, 1,3-benzodiazolyl, pyrimidinyl, tetrazolyl, 8-oxa-3-aza-bicyclo[3.2.1]octan-3-yl, pyridazinyl, oxazolyl, isoxazolyl, each of which may be unsubstituted or may be substituted with A, Hal, OR 3 , [C(R 3 )2] n Het 3 and / or may be mono-, di-, or trisubstituted by =O;

[0039] In Ij, R 1 H, Hal, CF3, NO2, A, [C(R 3 )2] n N(R 3 )2, [C(R 3 )2] n Het 1 , OR 3 , O[C(R 3 )2] n N(R3 )2, O[C(R 3 )2] n S(O) m R 3 , O[C(R 3 )2] n COOR 3 , O[C(R 3 )2] n COON(R 3 )2, O[C(R 3 )2] n Het 1 , O[C(R 3 )2] n Ph, or O[C(R 3 )2] n Cyc indicates R 2 indicates H or CH3, R 3 indicates H or A, V represents H or Hal; X is O or N(R 3 ) and Y represents phenylene, pyridine-diyl, thiophene-diyl, 1,3-thiazole-diyl, or pyrazole-diyl, each of which is unsubstituted or mono-, di-, or tri-substituted by Hal and / or A; Z is CON(R 3 )2, Phenyl, Het 4 , or -OA, Het 1are morpholinyl, tetrahydro-pyran-4-yl, tetrahydro-furan-3-yl, pyrrolidinyl, piperazinyl, piperidinyl, 6-oxa-3-azabicyclo[3.1.1]heptan-3-yl, pyridinyl, pyridazinyl, 2-oxa-6-azaspiro[3.3]heptan-6-yl, imidazolyl, azetidinyl, 3-aza-bicyclo[3.1.0]hexan-3-yl, 1 lambda 6-thiazolinyl, 2-oxa-6-azaspiro[3.3]heptan-6-yl, 2-oxa-6-azaspiro[3.1.0]hex ... omorpholinyl, 1l4-thiomorpholinyl, 1,3-dihydro-pyrrolo[3,4-c]pyridinyl, 3,8-diaza-bicyclo[3.2.1]octan-8-yl, 2l4-thia-5-aza-bicyclo[2.2.1]heptan-5-yl, [1,4]oxazepanyl, hexahydro-pyrazino[2,1-c][1,4]oxazin-8-yl, 5,6-dihydro-8H-[1,2,4]triazolo[4, 3-a]pyrazin-7-yl, 5,6-dihydro-8H-[1,2,4]triazolo[1,5-a]pyrazin-7-yl, 6-oxa-1-aza-spiro[3.3]heptan-1-yl, hexahydro-furo[3,2-b]pyridin-4-yl, hexahydro-pyrano[3,4-b][1,4]oxazin-1-yl, pyrazolyl, 1,4-diaza-bicyclo[3.2.1]octan-4-yl, 1,2 ,4-oxadiazolyl, 6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl, 6,7-dihydro-4H-[1,2,3]triazolo[1,5-a]pyrazin-5-yl, 3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-2-yl, 1,4-diazepanyl, triazolyl, or oxetanyl, each of which may be unsubstituted or may be selected from the group consisting of A, Hal, CN, OR 3 , [C(R 3 )2] n N(R 3 )2, [C(R 3 )2] n SO2R 3 , Het 2 , oxetanyl, =NR 3 and / or may be mono-, di-, or trisubstituted by =O, and wherein the N atom is optionally oxidized; Het 2represents furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, triazolyl, tetrazolyl, oxadiazolyl, pyridazinyl, pyrazinyl, 1,3-benzodiazolyl, 1,3-benzodioxolyl, indolyl, isoindolyl, or indazolyl, each of which may be unsubstituted or mono- or disubstituted by A and / or Hal; Het 3 denotes morpholinyl, pyrrolidinyl, piperidinyl, oxetanyl, or azetidinyl, each of which may be unsubstituted or may be substituted with A, Hal, OR 3 and / or may be mono- or disubstituted by =O, Het 4 represents pyrrolidinyl, 3-aza-bicyclo[3.1.0]hexan-3-yl, pyrazolyl, pyridinyl, imidazolyl, 4,5-dihydro-1H-imidazolyl, triazolyl, 4H,5H,6H-pyrrolo[1,2-b]pyrazol-3-yl, oxadiazolyl, 1,3-benzodiazolyl, pyrimidinyl, tetrazolyl, 8-oxa-3-aza-bicyclo[3.2.1]octan-3-yl, pyridazinyl, oxazolyl, isoxazolyl, each of which may be unsubstituted or may be substituted with A, Hal, OR 3 , [C(R 3 )2] n Het 3 and / or may be mono-, di-, or trisubstituted by ═O; A represents an unbranched or branched alkyl having 1 to 10 C atoms, in which 1 to 3 non-adjacent CH and / or CH groups may be replaced by O atoms or NH, and in which 1 to 7 H atoms are R 5 may be replaced by Or A is (CH2) n Cyc indicates Cyc represents a cyclic alkyl having 3 to 7 carbon atoms, R 5represents F, Cl, CN, or OH, Ph is optionally unsubstituted phenyl, or A, OR 3 and / or phenyl optionally mono-, di- or trisubstituted by Hal, Hal represents F, Cl, Br, or I; m is 0, 1, or 2; n represents 0, 1, 2, 3, or 4;

[0040] In Ik, R 1 are H, F, OCH2CH2OCH3, OCH3, CF3, O[C(R 3 )2] n N(R 3 )2, O[C(R 3 )2] n Het 1 , O[C(R 3 )2] n N(R 3 )Het 1 , OCH(CH2OCH3)2, O[C(R 3 )2] n Cyc, OCH2C(CH3)2OH, CH3, O[C(R 3 )2] n Ph, NO2, Cl, OH, OCH2C(CH3)2NH2, NHCH2C(CH3)2OH, [C(R 3 )2] n Het 1 , OCH2CH2OH, OCH2CH2CH2OH, O[C(R 3 )2] n S(O) m R 3 , or OCH2CH2OCH2CH2OH, and R 2 , R 3 ,V,X,Y,Z,Het 1 , Het 2 , Het 3 , Het 4 ,A,Cyc,R 5 , Ph, Hal, m, and n have the meanings as in sub-formula Ij;

[0041] In Im:R 1 is O[C(R 3 )2] n Het 1 , O[C(R 3 )2] n N(R 3 )Het 1 , or [C(R 3 )2] n Het 1 indicates, In:R 2 indicates H, In Io:R 3 indicates H or A, In Ip: V represents H, In Iq: X represents NH; In Ir: Y represents unsubstituted phenylene or phenylene mono-, di- or trisubstituted by Hal and / or A, In Is: Z is Het 4 or -OA,

[0042] In It:Het 1 represents tetrahydro-furan-3-yl, pyrrolidinyl, piperazinyl, piperidinyl, azetidinyl, imidazolyl, 6,7-dihydro-4H-[1,2,3]triazolo[1,5-a]pyrazin-5-yl, 1,4-diazepanyl, triazolyl, or oxetanyl, each of which may be unsubstituted or mono-, di-, or tri-substituted by A, Hal, oxetanyl, and / or ═O, and in which the N atom may be oxidized; In Iu:Het 4 represents pyrazolyl, triazolyl, or oxazolyl, each of which may be unsubstituted or mono-, di-, or tri-substituted by A, and / or In IV:R 5 represents F, Cl, or OH, In Iw: Hal represents F or Cl; Each subformula also includes its pharmaceutically acceptable salts, tautomers, and stereoisomers, and mixtures thereof in all proportions.

[0043] Thus, in one preferred embodiment, R 1 is O[C(R 3 )2] n Het 1 , O[C(R 3 )2] n N(R 3 )Het 1 , or [C(R 3 )2] n Het 1 and / or R 2 indicates H, and / or R 3 denotes H or A, and / or V indicates H, and / or X represents NH, and / or Y represents unsubstituted phenylene or phenylene mono-, di- or trisubstituted by Hal and / or A, and / or Z is for Het 4 or -OA and / or Het 1 denotes tetrahydro-furan-3-yl, pyrrolidinyl, piperazinyl, piperidinyl, azetidinyl, imidazolyl, 6,7-dihydro-4H-[1,2,3]triazolo[1,5-a]pyrazin-5-yl, 1,4-diazepanyl, triazolyl, or oxetanyl, each of which may be unsubstituted or mono-, di-, or tri-substituted by A, Hal, oxetanyl, and / or ═O, and in which the N atom may be oxidized, and / or Het 4 represents pyrazolyl, triazolyl, or oxazolyl, each of which may be unsubstituted or mono-, di-, or tri-substituted by A, and / or A represents an unbranched or branched alkyl having 1 to 10 C atoms, in which 1 to 3 non-adjacent CH and / or CH groups may be replaced by O atoms or NH, and in which 1 to 7 H atoms are R 5 may be replaced by Or A is (CH2) n Indicates Cyc, and / or Cyc denotes a cyclic alkyl having 3 to 7 C atoms, and / or R 5 denotes F, Cl, or OH, and / or Hal denotes F or Cl, and / or n is 0, 1, 2, 3, or 4, Any additional radicals and variables are defined as in Formula I or any of the subformulas above.

[0044] In one preferred embodiment of the compounds of formula I according to the present invention, R 1 is O[C(R 3 )2] n Het 1 , O[C(R 3 )2] n N(R 3 )Het 1 , [C(R 3 )2] n Het 1 indicates, R 2 indicates H, R 3 indicates H or A, V represents H, X represents NH; Y represents unsubstituted phenylene or phenylene mono-, di- or trisubstituted by Hal and / or A; Z is for Het 4 or -OA, Het 1represents tetrahydro-furan-3-yl, pyrrolidinyl, piperazinyl, piperidinyl, azetidinyl, imidazolyl, 6,7-dihydro-4H-[1,2,3]triazolo[1,5-a]pyrazin-5-yl, 1,4-diazepanyl, triazolyl, or oxetanyl, each of which may be unsubstituted or mono-, di-, or tri-substituted by A, Hal, oxetanyl, and / or ═O, and in which the N atom may be oxidized; Het 4 represents pyrazolyl, triazolyl, or oxazolyl, each of which may be unsubstituted or mono-, di-, or tri-substituted by A; A represents an unbranched or branched alkyl having 1 to 10 C atoms, in which 1 to 3 non-adjacent CH and / or CH groups may be replaced by O atoms or NH, and in which 1 to 7 H atoms are R 5 may be replaced by Or A is (CH2) n Cyc indicates Cyc represents a cyclic alkyl having 3 to 7 carbon atoms, R 5 represents F, Cl, or OH, Hal represents F or Cl; n is 0, 1, 2, 3, or 4; This equally refers to pharmaceutically acceptable salts, tautomers, and / or stereoisomers thereof.

[0045] Exemplary embodiments of compounds according to the present invention are set forth in Table 1 below, and are also intended to encompass pharmaceutically acceptable salts, tautomers, stereoisomers, and racemic mixtures, and solvates thereof. Table 1 [Table 1-1]

[0046] [Table 1-2]

[0047] Table 1-3

[0048] Table 1-4

[0049] Table 1-5

[0050] Table 1-6

[0051] Table 1-7

[0052] Table 1-8

[0053] Table 1-9

[0054] Table 1-10

[0055] Table 1-11

[0056] Table 1-12

[0057] [Table 1-13]

[0058] [Table 1-14]

[0059] [Table 1-15]

[0060] [Table 1-16]

[0061] [Table 1-17]

[0062] [Table 1-18]

[0063] [Table 1-19]

[0064] [Table 1-20]

[0065] Examples A75, A185, A217, and A258-268 are particularly preferred. Also preferred are those compounds found to have good solubility as described further below, and those listed in Table 3. The preparation and properties of these exemplary embodiments will be discussed further below.

[0066] The compounds of formula I, as well as the starting materials for their preparation, are additionally prepared by methods known per se, precisely under known and suitable reaction conditions, as described in the literature (e.g., standard scientific texts such as Houben-Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Georg-Thieme-Verlag, Stuttgart). Use may also be made of variants known per se, but not mentioned in detail here.

[0067] Formula I (wherein X is N(R 3 The compound of formula II, which represents a compound of formula III, can be preferably obtained by reacting a compound of formula II with a compound of formula III.

[0068] The starting compounds represented by formulas II and III are generally known. However, if they are new, they can be prepared by methods known per se. The reaction is generally carried out in the presence of hydroxides, carbonates or bicarbonates of alkali or alkaline earth metals, or other salts of weak acids of alkali or alkaline earth metals (preferably potassium, sodium, calcium or cesium), or in the presence of an organic base such as diisopropylamine (DIPEA). Preferably, the reaction is carried out in the presence of compounds such as K2CO3 and / or KI.

[0069] Depending on the conditions used, the reaction time is between a few minutes and 14 days, and the reaction temperature is between about -30° and 140°, usually between 60° and 130°, especially between about 80° and about 110°. Examples of suitable inert solvents include hydrocarbons such as hexane, petroleum ether, benzene, toluene or xylene; chlorinated hydrocarbons such as trichloroethylene, 1,2-dichloroethane, carbon tetrachloride, chloroform or dichloromethane; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol or tert-butanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF) or dioxane; glycol ethers such as ethylene glycol monomethyl ether or monoethyl ether, ethylene glycol dimethyl ether (diglyme); ketones such as acetone or butanone; amides such as acetamide, dimethylacetamide, 1-methylpyrrolidin-2-one or dimethylformamide (DMF); nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); carbon disulfide; carboxylic acids such as formic acid or acetic acid; nitro compounds such as nitromethane or nitrobenzene; esters such as ethyl acetate, or mixtures of these solvents.Specifically preferred is DMSO.

[0070] The compound represented by formula (I) can be preferably obtained by reacting a compound represented by formula (IV) with a compound represented by formula (V). The starting compounds represented by formulas (IV) and (V) are generally known. However, if they are new, they can be prepared by methods known per se. Preferably, the reaction is carried out in the presence of a compound such as N-bromosuccinimide (NBS). Depending on the conditions used, the reaction time is between a few minutes and 14 days, and the reaction temperature is between about -30° and 120°, usually between -10° and 80°, in particular between about -5° and about 70°. Examples of suitable inert solvents include hydrocarbons such as hexane, petroleum ether, benzene, toluene, or xylene; chlorinated hydrocarbons such as trichloroethylene, 1,2-dichloroethane, carbon tetrachloride, chloroform, or dichloromethane; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol, or tert-butanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF), or dioxane; glycol ethers such as ethylene glycol monomethyl ether or monoethyl ether, ethylene glycol dimethyl ether (diglyme); ketones such as acetone or butanone; amides such as acetamide, dimethylacetamide, 1-methylpyrrolidin-2-one, or dimethylformamide (DMF); nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); carbon disulfide; carboxylic acids such as formic acid or acetic acid; nitro compounds such as nitromethane or nitrobenzene; esters such as ethyl acetate, or mixtures of these solvents.Specifically preferred are 1,4-dioxane and / or water.

[0071] The compound of formula I is preferably a compound of formula I (wherein R 1 represents F) to prepare a compound represented by the formula (wherein R 1 is O[C(R 3 )2] n N(R 3 )2 or O[C(R 3 )2] n Het1 The compound may be obtained by converting the compound into another compound represented by the formula:

[0072] Formula I (wherein R 1 represents F) is an alcohol HO[C(R 3 )2] n N(R 3 )2(R in the formula 3 and n have the meaning as given above or in any of claims 1 to 8), or an alcohol HO[C(R 3 )2] n Het 1 (R in the formula 3 , Het 1 and n has the meaning as given above or in any of claims 1 to 8).

[0073] Preferably, the reaction is carried out using potassium tert-butanolate (KO tDepending on the conditions used, the reaction time is between a few minutes and 14 days, and the reaction temperature is between about -10° and 140°, usually between 0° and 120°, especially between about 20° and about 110°. Examples of suitable inert solvents include hydrocarbons such as hexane, petroleum ether, benzene, toluene, or xylene; chlorinated hydrocarbons such as trichloroethylene, 1,2-dichloroethane, carbon tetrachloride, chloroform, or dichloromethane; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol, or tert-butanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF), or dioxane; glycol ethers such as ethylene glycol monomethyl ether or monoethyl ether, ethylene glycol dimethyl ether (diglyme); ketones such as acetone or butanone; amides such as acetamide, dimethylacetamide, 1-methylpyrrolidin-2-one, or dimethylformamide (DMF); nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); carbon disulfide; carboxylic acids such as formic acid or acetic acid; nitro compounds such as nitromethane or nitrobenzene; esters such as ethyl acetate, or mixtures of these solvents. Particularly preferred is 1,4-dioxane.

[0074] Formula I (wherein Z is Het 4 The compound of formula VI, which represents a compound of formula VII, can be preferably obtained by reacting a compound of formula VI with a compound of formula VII.

[0075] The starting compounds of formulas VI and VII are generally known. However, if they are new, they can be prepared by methods known per se. The reaction is generally carried out in the presence of an alkali or alkaline earth metal hydroxide, carbonate, or bicarbonate, or another salt of a weak alkali or alkaline earth metal acid (preferably potassium, sodium, calcium, or cesium). Preferably, the reaction is carried out in the presence of a compound such as K2CO3. Depending on the conditions used, the reaction time is between a few minutes and 14 days, and the reaction temperature is between about -30° and 140°, usually between 60° and 130°, and more preferably between about 80° and about 110°. Examples of suitable inert solvents are hydrocarbons such as hexane, petroleum ether, benzene, toluene, or xylene; chlorinated hydrocarbons such as trichloroethylene, 1,2-dichloroethane, carbon tetrachloride, chloroform, or dichloromethane; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol, or tert-butanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF), or dioxane; glycol ethers such as ethylene glycol monomethyl or monoethyl ether, ethylene glycol dimethyl ether (diglyme); ketones such as acetone or butanone; amides such as acetamide, dimethylacetamide, 1-methylpyrrolidin-2-one, or dimethylformamide (DMF); nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); carbon disulfide; carboxylic acids such as formic acid or acetic acid; nitro compounds such as nitromethane or nitrobenzene; esters such as ethyl acetate, or mixtures of such solvents. Acetonitrile is particularly preferred.

[0076] Pharmaceutical Salts and Other Forms The compounds according to the present invention can be used in their final non-salt form, i.e., free form. On the other hand, the present invention also encompasses the use of these compounds in the form of their pharmaceutically acceptable salts, which can be derived from various organic and inorganic acids and bases by procedures known in the art. Most pharmaceutically acceptable salt forms of the compounds of Formula I are prepared by conventional methods. When the compound of Formula I contains a carboxyl group, a suitable salt can be formed by reacting the compound with a suitable base to give the corresponding base addition salt. Such bases include, for example, alkali metal hydroxides, including potassium hydroxide, sodium hydroxide, and lithium hydroxide; alkaline earth metal hydroxides, such as barium hydroxide and calcium hydroxide; alkali metal alkoxides, such as potassium ethoxide and sodium propoxide; and various organic bases, such as piperidine, diethanolamine, and N-methylglutamine. Aluminum salts of the compounds of Formula I are also encompassed. In the case of certain compounds of Formula I, acid addition salts may be formed by treating these compounds with pharmaceutically acceptable organic and inorganic acids, such as hydrogen halides (such as hydrogen chloride, hydrogen bromide, or hydrogen iodide), other mineral acids and their corresponding salts (such as sulfates, nitrates, or phosphates), and alkylsulfonates and monoarylsulfonates (such as ethanesulfonates, toluenesulfonates, and benzenesulfonates), and other organic acids and their corresponding salts, such as acetates, trifluoroacetates, tartrates, maleates, succinates (citrates, benzoates, salicylates, ascorbates, etc.).Consequently, pharmaceutically acceptable acid addition salts of the compounds of Formula I include the following: acetate, adipate, alginate, arginate, aspartate, benzoate, benzenesulfonate (besylate), bisulfate, bisulfite, bromide, butyrate, camphorate, camphorsulfonate, caprylate, chloride, chlorobenzoate, citrate, cyclopentanepropionate, digluconate, dihydrogenphosphate, dinitrobenzoate, dodecyl sulfate, ethanesulfonate, fumarate, formate, galactarate (from mucic acid), galacturonate, glucoheptanoate, gluconate, glutamate, glycerol, hydroxybenzoate ... The salts include, but are not limited to, phosphate, hemisuccinate, hemisulfate, heptanoate, hexanoate, hippurate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, iodide, isethionate, isobutyrate, lactate, lactobionate, malate, maleate, malonate, mandelate, metaphosphate, methanesulfonate, methylbenzoate, monohydrogenphosphate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, oleate, pamoate, pectinate, persulfate, phenylacetate, 3-phenylpropionate, phosphate, phosphonate, and phthalate.

[0077] Furthermore, basic salts of the compounds according to the present invention include, but are not intended to be limiting, aluminum, ammonium, calcium, copper, iron(III), iron(II), lithium, magnesium, manganese(III), manganese(II), potassium, sodium, and zinc salts. Of the above salts, preferred are ammonium, alkali metal salts (sodium and potassium), and alkaline earth metal salts (calcium and magnesium). Salts of the compounds of Formula I derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, salts of substituted amines, as well as naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as arginine, betaine, caffeine, chloroprocaine, choline, N,N'-dibenzylethylenediamine (benzathine), dicyclohexylamine, diethanolamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, Also included, but not intended to represent a limitation, are salts of N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lidocaine, lysine, meglumine, N-methyl-D-glucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethanolamine, triethylamine, trimethylamine, tripropylamine, and tris(hydroxymethyl)methylamine (tromethamine).

[0078] Compounds of the invention containing basic nitrogen-containing groups include (C1-C4) alkyl halides, such as methyl, ethyl, isopropyl, and tert-butyl chlorides, bromides, and iodides; di(C1-C4) alkyl sulfates, such as dimethyl sulfate, diethyl sulfate, and diamyl sulfate; (C 10 ~C 18) alkyl halides, such as decyl, dodecyl, lauryl, myristyl, and stearyl chlorides, bromides, and iodides; and aryl (C1-C4) alkyl halides, such as benzyl chloride and phenethyl bromide. Both water- and oil-soluble compounds according to the invention can be prepared using such salts.

[0079] Preferred such pharmaceutical salts include, but are not intended to represent a limitation, acetate, trifluoroacetate, besylate, citrate, fumarate, gluconate, hemisuccinate, hippurate, hydrochloride, hydrobromide, isethionate, mandelate, meglumine, nitrate, oleate, phosphonate, pivalate, sodium phosphate, stearate, sulfate, sulfosalicylate, tartrate, thiomalate, tosylate, and tromethamine.

[0080] Particularly preferred are the hydrochloride, dihydrochloride, hydrobromide, maleate, mesylate, phosphate, sulfate, and succinate salts.

[0081] Acid addition salts of basic compounds of Formula I are prepared in the conventional manner by contacting the free base form with a sufficient amount of the desired acid to cause the formation of the salt. The free base can be regenerated in the conventional manner by contacting the salt form with a base and isolating the free base. The free base forms differ in certain respects from their corresponding salt forms with respect to certain physical properties, such as solubility in polar solvents; however, for purposes of this invention, the salts otherwise correspond to their respective free base forms.

[0082] As mentioned, pharmaceutically acceptable base addition salts of the compounds of formula I are formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Preferred metals are sodium, potassium, magnesium, and calcium. Preferred organic amines are N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, N-methyl-D-glucamine, and procaine.

[0083] The base addition salts of acidic compounds according to the invention are prepared in the conventional manner by contacting the free acid form with a sufficient amount of the desired base to cause the formation of the salt. The free acid can be regenerated in the conventional manner by contacting the salt form with an acid and isolating the free acid. The free acid forms differ in certain respects from their corresponding salt forms with respect to certain physical properties, such as solubility in polar solvents; however, for purposes of this invention, the salts otherwise correspond to their respective free acid forms.

[0084] If the compound according to the present invention contains more than one group capable of forming pharmaceutically acceptable salts of this type, the present invention also encompasses multiple salts. Typical multiple salt forms include, for example, bitartrate, diacetate, difumarate, dimeglumine, diphosphate, disodium, and trihydrochloride, but this is not intended to represent a limitation.

[0085] As defined above, it is understood that the expression "pharmaceutically acceptable salt" in this context is to be understood as meaning an active ingredient comprising a compound of formula I in the form of one of its salts, especially if this salt form confers improved pharmacokinetic properties on the active ingredient compared to the free form of the active ingredient or any other salt form of the active ingredient previously used. A pharmaceutically acceptable salt form of an active ingredient can also confer on this active ingredient for the first time desired pharmacokinetic properties that it did not previously possess, and can even have a positive effect on the pharmacodynamics of this active ingredient with regard to its therapeutic effect in the body.

[0086] Isotopes Furthermore, compounds of Formula I are intended to encompass isotopically labeled forms thereof. Isotopically labeled forms of compounds of Formula I are identical to the compound except for the fact that one or more atoms of the compound have been replaced by an atom or atoms having an atomic mass or mass number different from the atomic mass or mass number of most naturally occurring atoms. Examples of isotopes that are readily commercially available and that can be incorporated into compounds of Formula I by well-known methods include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, e.g., 2 H, 3 H, 13 C. 14 C. 15 N, 18 O. 17 O. 31 P, 32 P, 35 S, 18 F, and 36 CI, respectively. Compounds of Formula I, prodrugs thereof, or pharmaceutically acceptable salts of either, that contain one or more of the above isotopes and / or other isotopes of other atoms are intended to be part of the present invention. Isotopically labeled compounds of Formula I can be used in a number of beneficial ways. For example, 3 H or 14 Isotopically labeled compounds of formula I, incorporating radioactive isotopes such as C, are suitable for drug and / or substrate tissue distribution assays. 3 H) and carbon-14 ( 14 C) is particularly preferred due to its simple preparation and excellent detectability. Heavier isotopes (e.g., deuterium ( 2Incorporation of H) into compounds of Formula I has therapeutic advantages due to the higher metabolic stability of the isotopically labeled compounds. Higher metabolic stability translates directly into increased in vivo half-life or lower dosages, which will represent a preferred embodiment of the present invention under most circumstances. Isotopically labeled compounds of Formula I can generally be prepared by carrying out the procedures disclosed in the synthetic schemes and related descriptions herein, in the Examples section, and in the Preparations section, replacing non-isotopically labeled reactants with readily available isotopically labeled reactants.

[0087] deuterium( 2 H) can also be incorporated into a target compound of Formula I to manipulate the compound's oxidative metabolism through the primary kinetic isotope effect. The primary kinetic isotope effect is the change in the rate of a chemical reaction due to the exchange of an isotope nucleus, which is secondary to the change in ground state energy required for covalent bond formation after this isotope exchange. The exchange of a heavier isotope usually results in a lowering of the ground state energy for the chemical bond, which in turn causes a reduction in the rate of rate-limiting bond breaking. If the bond breaking occurs in or near a saddle point region along the coordinate of a multi-product reaction, the product distribution ratio can be substantially altered. By way of illustration: when deuterium is attached to a carbon atom at a non-exchangeable position, k M / k D A rate difference of 2 to 7 is typical. If this rate difference is successfully applied to an oxidation-prone compound of formula I, the in vivo profile of the compound can be dramatically altered, resulting in improved pharmacokinetic properties.

[0088] When discovering and developing therapeutic agents, those skilled in the art attempt to optimize pharmacokinetic parameters while retaining desirable in vitro properties. It is reasonable to assume that many compounds with poor pharmacokinetic profiles are prone to oxidative metabolism. Currently available in vitro liver microsome assays provide valuable information about the course of this type of oxidative metabolism, which in turn allows for the rational design of deuterated compounds of Formula I with improved stability through resistance to such oxidative metabolism. Significant improvements in the pharmacokinetic profile of compounds of Formula I can thereby be obtained, improving in vivo half-life (t), concentration at maximum therapeutic effect (C), and other properties. max ), area under the dose-response curve (AUC), and F; and quantitatively in terms of reduced clearance, dose, and material cost.

[0089] The following is intended to illustrate what has been described above: A compound of Formula I, which has multiple potential attack sites for oxidative metabolism (e.g., benzylic hydrogen atoms and hydrogen atoms attached to nitrogen atoms), is prepared as a series of analogs in which various combinations of hydrogen atoms are replaced with deuterium atoms (so that some, most, or all of these hydrogen atoms can be replaced with deuterium atoms). Determination of half-life allows for a convenient and accurate determination of the extent to which resistance to oxidative metabolism has been improved. In this way, it is determined that the half-life of the parent compound can be extended by up to 100% as a result of this type of deuterium-hydrogen exchange.

[0090] Deuterium-hydrogen exchange in compounds of Formula I can also be used to achieve favorable modification of the metabolic spectrum of the starting compound to reduce or eliminate unwanted toxic metabolites. For example, if a toxic metabolite arises through oxidative carbon-hydrogen (C-H) bond cleavage, it can be reasonably expected that a deuterated analog will significantly reduce or eliminate the production of the unwanted metabolite, even if the specific oxidation is not the rate-limiting step. Further state-of-the-art information on deuterium-hydrogen exchange may be found, for example, in Hanzlik et al., J. Org. Chem. 55, 3992-3997, 1990; Reider et al., J. Org. Chem. 52, 3326-3334, 1987; Foster, Adv. Drug Res. 14, 1-40, 1985; Gillette et al., Biochemistry 33(10) 2927-2937, 1994; and Jarman et al. Carcinogenesis 16(4), 683-688, 1993.

[0091] The present invention also relates to medicaments comprising at least one compound of formula I and / or its pharmaceutically acceptable derivatives, solvates, stereoisomers and mixtures thereof in any ratio, and optionally excipients and / or adjuvants, which of course should be understood as including solvates of the compounds and salts.

[0092] Pharmaceutical preparations can be administered in the form of dosage units containing a predetermined amount of active ingredient per dosage unit. Such units can contain, for example, 0.5 mg to 1 g, preferably 1 mg to 700 mg, particularly preferably 5 mg to 100 mg of a compound according to the present invention, depending on the condition to be treated, the method of administration, and the patient's age, weight, and disease, or pharmaceutical preparations can be administered in the form of dosage units containing a predetermined amount of active ingredient per dosage unit. Preferred dosage unit formulations are those containing the daily dose or partial dose as indicated above, or a corresponding fraction thereof of the active ingredient. Furthermore, pharmaceutical preparations of this type can be prepared using processes commonly known in the pharmaceutical arts.

[0093] Pharmaceutical formulations can be adapted for administration via any suitable method desired, for example, oral (including buccal or sublingual), rectal, nasal, topical (including buccal, sublingual, or transdermal), vaginal, or parenteral (including subcutaneous, intramuscular, intravenous, or intradermal) administration. Such formulations can be prepared using any process known in the pharmaceutical art, for example, by combining the active ingredient with the excipient(s) or adjuvant(s).

[0094] Pharmaceutical formulations adapted for oral administration may be administered as discrete units, such as, for example, capsules or tablets; powders or granules; solutions or suspensions in aqueous or non-aqueous liquids; edible foams or foam foods; or oil-in-water or water-in-oil liquid emulsions.

[0095] Thus, for example, in the case of oral administration in the form of a tablet or capsule, the active ingredient component can be combined with an oral, non-toxic, and pharmaceutically acceptable inert excipient, such as, for example, ethanol, glycerol, water, etc. Powders are prepared by comminuting the compound to a suitable fine size and mixing it with a pharmaceutical excipient, such as, for example, an edible carbohydrate, such as, for example, starch or mannitol, comminuted in a similar manner. Flavors, preservatives, dispersants, and dyes can also be present.

[0096] Capsules are produced by preparing a powder mixture as described above and filling it into formed gelatin shells. For example, glidants and lubricants, such as silicic acid, talc, magnesium stearate, calcium stearate, or polyethylene glycol, which are highly dispersible in solid form, can be added to the powder mixture before filling. Disintegrants or solubilizers, such as agar-agar, calcium carbonate, or sodium carbonate, can also be added to improve the availability of the medicament after the capsule is taken.

[0097] Additionally, if desired or necessary, suitable binders, lubricants, disintegrants, and dyes may also be incorporated into the mixture. Suitable binders include starch, gelatin, natural sugars (such as glucose or beta-lactose), corn sweeteners, natural and synthetic gums (such as acacia, tragacanth, or sodium alginate), carboxymethylcellulose, polyethylene glycol, waxes, and the like. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methylcellulose, agar, bentonite, xanthan gum, and the like. Tablets are formulated, for example, by preparing a powder mixture, granulating or dry-pressing the mixture, adding a lubricant and disintegrant, and compressing the entire mixture to give tablets. Powder mixtures are prepared as described above by mixing the powdered compound with a diluent or base, and optionally with binders (such as, for example, carboxymethylcellulose, alginate, gelatin, or polyvinylpyrrolidone), solution retarders (such as, for example, paraffin), absorption enhancers (such as, for example, quaternary salts), and / or absorbents (such as, for example, bentonite, kaolin, or dicalcium phosphate). The powder mixture can be granulated by wetting it with a binder (such as, for example, syrup, starch paste, acacia mucilage, or solutions of cellulose or polymer materials) and pressing it through a sieve. As an alternative to granulating, the powder mixture can be passed through a tablet press, giving irregularly shaped lumps which can be broken up to form granules. The granules can be lubricated to prevent sticking to the tablet dies by adding stearic acid, a stearate salt, talc, or mineral oil. The lubricated mixture is then compressed to give tablets. The compounds according to the invention can also be combined with a free-flowing inert excipient and then compressed directly to give tablets, without carrying out either the granulation or dry-pressing steps.A clear or opaque protective layer consisting of a shellac sealing layer, a layer of sugar or polymer material, and a gloss layer of wax may be present. Dyes can be added to these coatings in order to be able to distinguish between different dosage units.

[0098] Oral liquids, such as solution, syrup and elixir, can be prepared in dosage unit form, so that a predetermined amount contains a predetermined amount of compound.Syrup can be prepared by dissolving compound in aqueous solution with suitable flavor, while elixir is prepared using non-toxic alcoholic vehicle.Suspension can be prepared by dispersing compound in non-toxic vehicle.Solubilizer and emulsifier (such as ethoxylated isostearyl alcohol and polyoxyethylene sorbitol ether), preservative, flavor additive (such as peppermint oil, or natural sweetener or saccharin, or other artificial sweetener, etc.) can also be added.

[0099] Dosage unit formulations for oral administration can, if desired, be encapsulated in microcapsules. Formulations can also be prepared so as to provide extended or delayed release, for example, by coating or embedding particulate materials in polymers, waxes, etc.

[0100] The compounds of Formula I, and their pharmaceutical salts, tautomers, and stereoisomers, can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. Liposomes can be formed from various phospholipids, such as cholesterol, stearylamine, or phosphatidylcholines.

[0101] The compounds of Formula I, as well as their salts, tautomers, and stereoisomers, can also be delivered using monoclonal antibodies as individual carriers to which the compound molecules are coupled. The compounds can also be coupled to soluble polymers as targeted drug carriers. Such polymers include polyvinylpyrrolidone, pyran copolymers, polyhydroxypropylmethacrylamidephenol, polyhydroxyethylaspartamidophenol, or polyethylene oxide polylysine substituted with palmitoyl radicals. The compounds can also be coupled to a class of biodegradable polymers suitable for achieving controlled drug release, such as polylactic acid, poly-epsilon-caprolactone, polyhydroxybutyric acid, polyorthoesters, polyacetals, polydihydroxypyrans, polycyanoacrylates, and crosslinked or amphiphilic hydrogel block copolymers.

[0102] Pharmaceutical formulations adapted for transdermal administration can be administered as independent patches for prolonged contact with the epidermis of the recipient. Thus, for example, the active ingredient can be delivered from the patch by iontophoresis, as described in general terms in Pharmaceutical Research, 3(6), 318 (1986).

[0103] Pharmaceutical compounds adapted for topical administration can be formulated as ointments, creams, suspensions, lotions, powders, solutions, pastes, gels, sprays, aerosols, or oils.

[0104] For the treatment of the eye or other external tissues, for example, the mouth and skin, the formulations are preferably applied as topical ointments or creams.In the case of formulations to give an ointment, the active ingredient can be employed with either a paraffinic or water-miscible cream base.Alternatively, the active ingredient can be formulated to give a cream with an oil-in-water cream base or a water-in-oil base.

[0105] Pharmaceutical formulations adapted for topical application to the eye include eye drops, in which the active ingredient is dissolved or suspended in a suitable carrier, especially an aqueous solvent. Pharmaceutical formulations adapted for topical application in the mouth encompass lozenges, troches, and mouthwashes.

[0106] Pharmaceutical formulations adapted for rectal administration can be administered in the form of suppositories or enemas. Pharmaceutical formulations adapted for nasal administration, in which the carrier substance is a solid, include coarse powders, for example, having a particle size in the range of 20 to 500 microns, and are administered in the manner in which snuff is taken, i.e., by rapid inhalation through the nasal passages from a powder-containing container held close to the nose. Formulations suitable for administration as nasal sprays or nasal drops, with a liquid as the carrier substance, include solutions of the active ingredient in water or oil. Pharmaceutical formulations adapted for administration by inhalation include finely particulate dusts or mists, which can be generated by various types of pressurized dispensers with aerosols, nebulizers, or inhalers. Pharmaceutical formulations adapted for vaginal administration can be administered as suppositories, tampons, creams, gels, pastes, foams, or spray formulations.

[0107] Pharmaceutical preparations adapted for parenteral administration include aqueous and non-aqueous sterile injection solutions containing antioxidants, buffers, bacteriostats, and solutes that render the preparation isotonic with the blood of the recipient to be treated; and aqueous and non-aqueous sterile suspensions, which may contain a suspending medium and a thickening agent. The preparations may be provided in single-dose or multi-dose containers (e.g., sealed ampoules and vials) and may be stored in a freeze-dried (lyophilized) state, requiring only the addition of a sterile carrier liquid (e.g., water for injection) immediately prior to use. Injection solutions and suspensions prepared according to a recipe may be prepared from sterile powders, granules, and tablets.

[0108] It will be appreciated that in addition to the constituents specifically mentioned above, the formulations may also include other agents customary in the art with respect to the particular type of formulation; thus, for example, formulations suitable for oral administration may include flavors.

[0109] The therapeutically effective amount of a compound of Formula I depends on numerous factors, including, for example, the age and weight of the animal, the precise disease requiring treatment and its severity, the nature of the formulation, and the method of administration, and is ultimately determined by the treating physician or veterinarian. However, an effective amount of a compound according to the present invention will generally be in the range of 0.1 to 100 mg / kg of recipient (mammal) body weight per day, and more typically in the range of 1 to 10 mg / kg of recipient (mammal) body weight per day. Thus, for an adult mammal weighing 70 kg, the practical daily amount will often be between 70 mg and 700 mg, which may be administered as a single dose or, in most cases, in a series of partial doses (e.g., 2, 3, 4, 5, or 6 doses) per day so that the total daily dose is the same. An effective amount of a salt or solvate thereof, or an effective amount of a physiologically functional derivative thereof, may be determined as a fraction of the effective amount of the compound according to the present invention itself. It can be assumed that similar doses would be suitable for the treatment of the other diseases mentioned above.

[0110] This type of combination treatment may be achieved by utilizing simultaneous, sequential, or separate administration of the individual components of the treatment. This type of combination product employs a compound according to the present invention.

[0111] The present invention also relates to a medicament comprising at least one compound of formula I, and / or its pharmaceutically acceptable salts, tautomers, and stereoisomers, and mixtures thereof in any ratio, and at least one additional pharmaceutically active ingredient (synonymous with active pharmaceutical ingredient).

[0112] The present invention also provides (a) an effective amount of a compound of Formula I, and / or its pharmaceutically acceptable salts, tautomers, and stereoisomers, and mixtures thereof in all ratios; and (b) an effective amount of a further pharmaceutically active ingredient; It also relates to a set (kit) consisting of separate packs of:

[0113] The kit comprises suitable containers, such as boxes, individual bottles, bags, or ampoules, which may, for example, contain separate ampoules, each containing an effective amount of a compound of Formula I, and / or its pharmaceutically acceptable salts, tautomers, and stereoisomers, and mixtures thereof in any ratio, and an effective amount of a further pharmaceutically active ingredient in dissolved or lyophilized form.

[0114] "Treating," as used herein, means the total or partial alleviation of symptoms associated with a disorder or disease, or the slowing or halting of further progression or worsening of those symptoms, or the prevention or prophylaxis of a disease or disorder in a subject at risk of developing the disease or disorder.

[0115] The term "effective amount" in reference to a compound of Formula I may mean an amount that is capable of alleviating, in whole or in part, the symptoms associated with a disorder or disease, or slowing or halting the further progression or worsening of those symptoms, or preventing or providing prophylaxis for a disease or disorder in a subject having or at risk of developing a disease disclosed herein (such as an inflammatory disease, immunological disease, cancer, or metabolic disease).

[0116] The phrase "effective amount" refers to an amount of a drug or an amount of a pharmaceutical active ingredient that elicits the biological or medical response sought or desired, for example, by a researcher or physician, in a tissue, system, animal, or human. Additionally, the phrase "therapeutically effective amount" refers to an amount that has the following consequences: improved treatment, cure, prevention, or elimination of a disease, syndrome, illness, complaint, disorder, or side effect, or even a reduction in the prevalence of a disease, complaint, or disorder, compared to a corresponding subject not receiving this amount.

[0117] The expression "therapeutically effective amount" also encompasses the amounts which are effective for increasing normal physiological function.

[0118] In one embodiment, an effective amount of a compound of Formula I is an amount that inhibits c-KIT kinase in cells, e.g., in vitro or in vivo. In some embodiments, an effective amount of a compound of Formula I inhibits c-KIT in cells by 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 99% compared to the activity of c-KIT kinase in untreated cells. An effective amount of a compound of Formula I may be, for example, in a pharmaceutical composition, at a level that will produce the desired effect; for example, about 0.005 mg / kg (of the subject's body weight) to about 10 mg / kg (of the subject's body weight) in a unit dosage for both oral and parenteral administration.

[0119] use The compounds are suitable for mammals, particularly humans, as active pharmaceutical ingredients in the treatment of cancers such as gastrointestinal stromal tumors. The present invention covers the use of compounds of formula I, and / or their pharmaceutically acceptable salts, tautomers, and stereoisomers, for the preparation of a medicament for the treatment or prevention of cancer, preferably for the treatment of gastrointestinal stromal tumors.

[0120] Preferably, the present invention relates to a method for treating a disease, wherein the disease is cancer, preferably gastrointestinal stromal tumor. Specifically and preferably, the present invention relates to methods wherein the disease is cancer, and wherein administration is simultaneous, sequential, or alternating with administration of at least one other active pharmaceutical agent.

[0121] The disclosed compounds of Formula I can be administered in combination with other known therapeutic agents, including anti-cancer agents. As used herein, the term "anti-cancer agent" refers to any agent administered to a cancer patient for the purpose of treating the cancer.

[0122] The anti-cancer treatment defined above may be applied as a monotherapy or may involve, in addition to the compound of formula I disclosed herein, conventional surgery or radiation therapy or medicinal therapy. Such medicinal therapy (e.g., chemotherapy or targeted therapy) may include one or more, preferably one of the following anti-tumor agents:

[0123] Alkylating agents Altretamine, bendamustine, busulfan, carmustine, chlorambucil, chlormethine, cyclophosphamide, dacarbazine, ifosfamide, improsulfan, tosilate, lomustine, melphalan, mitobronitol, mitolactol, nimustine, ranimustine, temozolomide, thiotepa, treosulfan, mechlorethamine, carboquone; Apaziquone, fotemustine, glufosfamide, palifosfamide, pipobroman, trofosfamide, uramustine, TH-302 4 , VAL-083 4 etc;

[0124] platinum compound Carboplatin, cisplatin, eptaplatin, miriplatin hydrate, oxaliplatin, lobaplatin, nedaplatin, picoplatin, satraplatin; lobaplatin, nedaplatin, picoplatin, satraplatin, etc.; DNA modifying agents Amrubicin, bisantrene, decitabine, mitoxantrone, procarbazine, trabectedin, clofarabine; Amsacrine, brostallicin, pixantrone, laromustine 1,3 etc;

[0125] Topoisomerase inhibitors Etoposide, irinotecan, razoxane, sobuzoxane, teniposide, topotecan; amonafide, belotecan, elliptinium acetate, voreloxin, etc.; Microtubule modifier: Cabazitaxel, docetaxel, eribulin, ixabepilone, paclitaxel, vinplastine, vincristine, vinorelbine, vindesine, vinflunine; Fosbretabline, tesetaxel, etc.

[0126] anti-metabolite Asparaginase 3 , azacitidine, levofolinate calcium, capecitabine, cladribine, cytarabine, enocitabine, floxuridine, fludarabine, fluorouracil, gemcitabine, mercaptopurine, methotrexate, nelarabine, pemetrexed, pralatrexate, azathioprine, thioguanine, carmofur; Doxifluridine, elacitabine, raltitrexed, cepacitabine, tegafur 2,3 , trimethotrexate, etc.;

[0127] Anticancer antibiotics Bleomycin, dactinomycin, doxorubicin, epirubicin, idarubicin, levamisole, miltefosine, mitomycin C, romidepsin, streptozocin, valrubicin, zinostatin, zorubicin, daunorubicin, plicamycin; Aclarubicin, peplomycin, pirarubicin, etc.;

[0128] Hormones / antagonists Abarelix, abiraterone, bicalutamide, buserelin, calsterone, chlorotonianicene, degarelix, dexamethasone, estradiol, flutocortolone, fluoxymesterone, flutamide, fulvestrant, goserelin, histrelin, leuprorelin, megesterol, mitotane, nafarelin, nandrolone, nilutamide, octreotide, prednisolone, raloxifene, tamoxifen, thyrotropin alfa, toremifene, trilostane, triptorelin, diethylstilbestrol; Acolbifene, danazol, deslorelin, epithiostanol, orteronel, enzalutamide 1,3 etc;

[0129] Aromatase inhibitors Aminoglutethimide, anastrozole, exemestane, fadrozole, letrozole, testolactone; Holmestan, etc.;

[0130] Small Molecule Kinase Inhibitors Crizotinib, dasatinib, erlotinib, imatinib, lapatinib, nilotinib, pazopanib, regorafenib, ruxolitinib, sorafenib, sunitinib, vandetanib, vemurafenib, bosutinib, gefitinib, axitinib; Afatinib, alisertib, dabrafenib, dacomitinib, dinaciclib, dovitinib, enzastaurin, nintedanib, lenvatinib, linifanib, lincitinib, masitinib, midostaurin, motesanib, neratinib, orantinib, perifosine, ponatinib, radotinib, rigosertib, tipifanib, tivantinib, tivozanib, trametinib, pimasertib, brivanimab alaninate, cediranib, apatinib 4 , Cabozantinib S-malate 1,3 , ibrutinib 1,3 , icotinib 4 , buparlisib 2 , cipatinib 4 , cobimetinib1,3 , idelalisib 1,3 , fedratinib 1 , XL-647 4 etc;

[0131] Photosensitizers Methoxsalen 3 ; Porfimer sodium, talaporfin, temoporfin, etc.; antibody Alemtuzumab, besilesomab, brentuximab vedotin, cetuximab, denosumab, ipilimumab, ofatumumab, panitumumab, rituximab, tositumomab, trastuzumab, bevacizumab, pertuzumab 2,3 ; Catumaxomab, elotuzumab, epratuzumab, farletuzumab, mogamulizumab, necitumumab, nimotuzumab, obinutuzumab, ocalatuzumab, oregovomab, ramucirumab, rilotumumab, siltuximab, tocilizumab, zalutumumab, zanolimumab, matuzumab, dalotuzumab 1,2,3 , onartuzumab 1,3 , racotumomab 1 , Tabalumab 1,3 , EMD-525797 4 , nivolumab 1,3 etc;

[0132] cytokines Aldesleukin, interferon alfa 2 , interferon alpha 2a 3 , interferon alfa-2b 2,3 ; Celmoleukin, tasonermin, teseleukin, operelvekin 1,3 , recombinant interferon beta-1a 4 etc; Drug conjugates Denileukin diftitox, ibritumomab tiuxetan, iobenguane I123, prednimustine, trastuzumab emtansine, estramustine, gemtuzumab, ozogamicin, aflibercept; Syntredequin besudotox, edotreotide, inotuzumab ozogamicin, naptumomab estafenatox, oportuzumab monatox, technitium (99mTc) arcitumomab 1,3 , vintaphorid 1,3 etc;

[0133] vaccine Sipuleucel 3 ;Vitespen 3 , Emepepimt-S 3 , OncoVAX 4 , Lindopepimt 3 , troVax 4 , MGN-1601 4 , MGN-1703 4 etc; others Alitretinoin, bexarotene, bortezomib, everolimus, ibandronate, imiquimod, lenalidomide, lentinan, metyrosine, mifamurtide, pamidronate, pegaspargase, pentostatin, sipuleucel 3 , sizofiran, tamibarotene, temsirolimus, thalidomide, tretinoin, vismodegib, zoledronic acid, vorinostat; Celecoxib, cilengitide, entinostat, etanidazole, ganetespib, idronoxyl, iniparib, ixazomib, lonidamine, nimorazole, parabinostat, peretinoin, plitidepsin, pomalidomide, procodazol, ridaforolimus, tasquinimod, telotristat, simalfasin, tirapazamine, tosedostat, travedelsen, ubenimex, valspodar, and gendicine 4 , Picibanil 4 , leiolysin 4 , letaspimycin hydrochloride1,3 , trebananib 2,3 , bilirudin 4 , carfilzomib 1,3 , endostatin 4 , Immucothel 4 , Belinostat 3 , MGN-1703 4 ;

[0134] 1 Prop.INN (Proposed International Nonproprietary Name) 2 Rec.INN (Recommended International Nonproprietary Name) 3 USAN (United States Adopted Name) 4 No INN.

[0135] Furthermore, the present invention provides: 6-chloro-N-{[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-methyl}-pyrimidin-4-amine [ka] 6-[I-2-Ethoxyethenyl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine [ka] 4-chloro-6-[(E)-2-ethoxyethenyl]pyrimidine [ka] 4-chloro-6-{7-fluoroimidazo[1,264-pyridindin-3-yl]pyrimidine [ka] The present invention relates to an intermediate selected from

[0136] The following abbreviations are used throughout this specification: aq (aqueous), h (hour), g (gram), L (liter), mg (milligram), MHz (megahertz), min. (minute), mm (millimeter), mmol (millimole), mM (millimole), mp (melting point), eq (equivalent), ml (milliliter), μl (microliter), ACN (acetonitrile), AcOH (acetic acid), CDCl3 (deuterated chloroform), CD3OD (deuterated methanol), CH3CN (acetonitrile), c-hex (cyclohexane), DCC (dicyclohexylcarbodiimide) amide), DCM (dichloromethane), DIC (diisopropylcarbodiimide), DIPEA (diisopropylethylamine), DMF (dimethylformamide), DMSO (dimethyl sulfoxide), DMSO-d6 (deuterated dimethyl sulfoxide), EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, ESI (electrospray ionization), EtOAc (ethyl acetate), Et2O (diethyl ether), EtOH (ethanol), HATU (dimethylamino-([1,2,3 ]triazolo[4,5-b]pyridin-3-yloxy)-methylene]-dimethyl-ammonium hexafluorophosphate), HPLC (High Performance Liquid Chromatography), i-PrOH (2-propanol), K2CO3 (potassium carbonate), LC (Liquid Chromatography), MeOH (methanol), MgSO4 (magnesium sulfate), MS (Mass Spectrometry), MTBE (Methyl tert-butyl ether), NaHCO3 (sodium bicarbonate), NaBH4 (sodium borohydride), NMM (N-methyl monomethyl ether), fluoroline), NMR (Nuclear Magnetic Resonance), PyBOP (Benzotriazol-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate, RT (Room Temperature), Rt (Retention Time), SPE (Solid Phase Extraction), TBTU (2-(1-H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate), TEA (Triethylamine), TFA (Trifluoroacetic Acid), THF (Tetrahydrofuran), TLC (Thin Layer Chromatography), UPLC (Ultra Performance Liquid Chromatography), UV (Ultraviolet). Above and below, all temperatures are given in °C.

[0137] 1 H NMR was recorded on a Bruker DPX-300, DRX-400, AVII-400, or 500 MHz spectrometer using the residual signal of the deuterated solvent as an internal reference. Chemical shifts (δ) were recorded on a Bruker DPX-300, DRX-400, AVII-400, or 500 MHz spectrometer using the residual signal of the deuterated solvent as an internal reference. 1 All values ​​are reported in ppm relative to 1 H NMR (δ=2.49 ppm). 1 H NMR data are reported as follows: chemical shifts (multiplicities, coupling constants, and hydrogen numbers). Multiplicities are abbreviated as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad), bs (broad singlet), p (quintet).

[0138] HPLC / MS Condition A: HPLC / MS: Agilent 1200 / 6100 Eluent A: Water + 0.05% formic acid Eluent B: Acetonitrile + 0.04% formic acid Column: Chromolith HR RP-18e; 50-4.6 mm Flow rate: 3.3ml / min Gradient: 0% → 100%B: 0.0 → 2.0 min | 100%B: 2.0 → 2.5 min UV detection: 220 nm MS detection: 65-800amu positive

[0139] HPLC / MS condition B: HPLC / MS: Agilent 1200 / 6100 Eluent A: Water + 0.05% formic acid Eluent B: Acetonitrile + 0.04% formic acid + 1% H2O Column: Kinetex XB-C18; 2.6 μm; 50-4.6 mm Flow rate: 3.3ml / min Column temperature: 40℃ Gradient: 1% → 99%B: 0.0 → 0.8 min | 99%B: 0.8 → 1.1 min UV detection: 220 nm MS detection: 65-800 amu positive

[0140] UPLC / MS conditions: UPLC / MS:Waters Acquity / SQD Eluent A: Water + 0.05% formic acid Eluent B: Acetonitrile + 0.04% formic acid + 1% H2O Column: Kinetex XB-C18; 1.7 μm; 50-2.1 mm Flow rate: 0.9ml / min Gradient: 1% → 99%B: 0.0 → 1.0 min | 99%B: 1.0 → 1.3 min Column temperature: 40℃ UV detection: 220 nm MS detection: 61-800 amu positive + 46-1000 amu negative

[0141] Assays and Measurements c-Kit(V654A) assay: c-Kit(V654A) (recombinant human c-Kit tagged with GST at the N-terminus, containing the V654A mutation at amino acid 544-terminal) is incubated with 8 mM MOPS (pH 7.0), 0.2 mM EDTA, 250 μM GGMEDIYEFMGGKKK, 10 mM Mg acetate, and [gamma-33P-ATP] (specific activity approximately 500 cpm / pmol, concentration 200 μM). The reaction is initiated by the addition of the MgATP mix. After a 40-minute incubation at room temperature, the reaction is stopped by the addition of a 3% phosphoric acid solution. 10 μL of the reaction is then spotted onto a P30 filtermat and washed three times for 5 minutes in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting.

[0142] Assay principle for cellular testing of cKIT mutant inhibitors The GIST430 cell line, which expresses a constitutively active cKIT receptor tyrosine kinase (Δ560-576 deletion), and the imatinib-resistant GIST430 / 654 cell line, which expresses a constitutively active mutant cKIT receptor tyrosine kinase (Δ560-576 deletion and V654A point mutation), were employed to assess the cellular efficacy of compounds. The cellular activity of mutant cKIT was determined by the degree of cKIT autophosphorylation at tyrosine 307 using a Luminex-based bead assay. GIST430 cells were seeded at 22,000 cells per well of a 96-well plate in 100 μl of medium (85% IMDM / 15% FCS), and GIST430 / 654 cells were seeded at 25,000 cells per well of a 96-well plate in 100 μl of medium (85% IMDM / 15% FCS supplemented with 100 nM imatinib). The following day, compounds were added in serial dilutions for 45 min. The cells were then lysed in 90 μl lysis buffer (20 mM Hepes (pH 7.5), 200 mM NaCl, 1.5 mM MgCl2 × 6H2O, 0.4 mM EDTA, 1% Triton-X-100, 1% Phosphatase Inhibitor II, 20 mM β-glycerol phosphatase, 0.1% Protease Inhibitor Cocktail III, 0.01% Benzonase), and the lysates were clarified by centrifugation through a 96-well filter plate (0.65 μm). The samples were incubated overnight at 4°C with Luminex beads coupled with anti-total cKIT antibody under gentle agitation. For detection of phospho-Y307-cKIT, a phospho-specific antibody and a species-specific PE-labeled secondary antibody were added. The amount of phospho-Y307-cKIT was measured in a Luminex 200 instrument measuring 100 events per well within 60 seconds.

[0143] Counts from compound-treated samples were calculated as a percentage of the control from vehicle (0.3% DMSO)-treated samples. Dose-response curves were fitted and IC 50Values ​​were determined using Genedata Screener software.

[0144] Determination of efflux ratio (ER) in Caco-2 cells The efflux rate of the test compound was calculated as the apparent permeability (P app The chromatin concentration was determined in the Caco-2 human epithelial colorectal adenocarcinoma cell line (TC7 clone) using the chromatin concentration (ΔΨ) calculation. Cell monolayers were differentiated in vitro for 14 days prior to the experiment. Test compounds (at a final concentration of 1 μM in HBSS, pH 7.4) were then applied to the donor side, while HBSS buffer (pH 7.4) was added to the receiver wells. The final DMSO concentration during the incubation did not exceed 1%. The plates were then incubated in a 5% CO2 incubator (37°C, 100% humidity). At the end of the 2-hour incubation period, 50 μL samples were removed from both the donor and receiver wells and diluted 1:1 with an equal volume of acetonitrile for LC-MS / MS analysis. LC-MS / MS analysis used a one-point calibration method from a 1 μM standard solution diluted 1:1 with an equal volume of acetonitrile (matching the test sample).

[0145] The data was used to calculate the apparent permeability of the compound from apical to basolateral (P app,AB ) direction and basolateral to apical (P app,BA ) direction and at a concentration of 1 μM. app Values ​​were calculated from the concentrations in the donor and receiver compartments using the following formula:

number

number

[0146] Determination of solubilization degree In a 96-well filtration plate, 2 μL of a 10 mM solution of test compound in DMSO is added to 98 μL of 20 mM Sorensen's phosphate buffer (pH 7.4). The mixture is incubated at room temperature for 120 min with stirring at 250 rpm, followed by centrifugation at 2500 rpm for 3 min. After dilution by a factor of 2, the concentration of the test compound is determined by comparing with the corresponding standard compound using HPLC / UPLC with detection at a suitable wavelength.

[0147] example In certain exemplary embodiments, compounds are prepared according to the following general procedures, as depicted and described in the examples below. While the general methods illustrate the synthesis of certain compounds of the present invention, it will be understood that the following general methods, as well as other methods known to those of skill in the art, can be applied to all compounds as described herein, as well as each subclass and species of these compounds.

[0148] The following data, determined by the assays described above and set forth in Tables 2 and 3 below, illustrate the efficacy of embodiments of the present invention in terms of inhibition of cKit(V654A) GIST430 / 654, respectively. As can be seen from the tables, the compounds exhibited excellent IC 50 These compounds have potent potent potency, many of which are in the low nanomolar concentration range. In addition, the compounds are selective, particularly compared to the closely related kinase FLT3 ("fms-like tyrosine kinase 3"). Embodiments tested against a broader panel of kinases (including JAKs) have been found to show significantly better selectivity than those kinases.

[0149] In addition to excellent inhibitory potency, certain preferred embodiments of the present invention have been found to possess a balance of promising pharmacokinetic properties (including bioavailability) as experimentally determined by solubilization and efflux, with acceptable to excellent levels of unwanted blockage of the hERG potassium channel. The results of the experimental efflux measurements are provided in Table 4 below.

[0150] Exemplary embodiments A8, A12, A15, A60, A73, A75, A83, A84, A99, A100, A102, A120, A149, A153, A154, A156, A168, A170, A212, A242, and A252 were determined to have a preferred solubility of at least 25 μM.

[0151] Pharmacological Data Table 2. Inhibition of c-KIT(V654A) and GIST430 / 654 (IC) of compounds represented by formula I 50 ) [Table 2-1]

[0152] [Table 2-2]

[0153] [Table 2-3]

[0154] [Table 2-4]

[0155] [Table 2-5]

[0156] [Table 2-6]

[0157] Table 3. Inhibition of GIST430 (IC) of compounds represented by formula I 50 ) [Table 3] Explanation: 1,4E-06 is 1.4 x 10 -6 Therefore, "E" represents "a power of 10."

[0158] Table 4 [Table 4-1]

[0159] [Table 4-2] A:≦15; B:>15~50; C>50

[0160] Synthesis of intermediates Arylmethylamines Synthesis of 1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]-methanamine (D1) [ka] To a solution of N-Boc-4-bromobenzylamine (29.4 g, 103 mmol) in 1,2-dimethoxyethane (275 ml), 1-methyl-1H-pyrazole-4-boronic acid pinacol ester (25.5 g, 122.6 mmol), water (105 ml), and sodium carbonate (16.3 g, 154 mmol) are added, and the resulting suspension is flushed with argon. Bis(triphenylphosphine)palladium(II) chloride (2.9 g, 4.13 mmol) is added under argon. The mixture is heated to 80 °C and stirred at this temperature for 2 days. When the reaction mixture reaches room temperature, it is treated with water and ethyl acetate. The organic phase is separated, and the aqueous phase is extracted twice with ethyl acetate. The combined organic phases are dried over sodium sulfate and evaporated. The residue was chromatographed on a silica gel column using cyclohexane / ethyl acetate as the eluent to give tert-butyl N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}carbamate as a pale yellow crystalline solid; UPLC / MS 0.709 min, [M+H] + 288. 1 H NMR(400MHz,DMSO-d6)δ8.07(s,1H),7.81(s,1H),7.49(d,J=8.0Hz,2H),7.33(t,J= 6.3Hz,1H),7.20(d,J=8.1Hz,2H),4.09(d,J=6.2Hz,2H),3.85(s,3H),1.39(s,9H).

[0161] To a solution of tert-butyl N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}carbamate (24.7 g, 85.6 mmol) in 1,4-dioxane (170 ml) was added a 4N solution of hydrogen chloride in dioxane, and the mixture was stirred at room temperature for 18 hours. The resulting precipitate was filtered off, washed with tert-butyl methyl ether, and dried under vacuum to give 1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methanamine dihydrochloride as a pale yellow powder; UPLC / MS 0.286 min, [M-NH2] + 171.

[0162] To a solution of 1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methanamine dihydrochloride (22.4 g, 86.0 mmol) in water (500 ml) was added dropwise 2N aqueous sodium hydroxide (129 ml) with stirring. The resulting precipitate was filtered off, washed with water, and dried under vacuum at 50 °C for 3 days to give 1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methanamine as a light brown powder; UPLC / MS 0.286 min, [M-NH2] + 171. 1 H NMR(400MHz,DMSO-d6)δ8.08(d,J=0.8Hz,1H),7.82(d,J=0.8Hz,1H),7.48(d ,J=8.2Hz,2H),7.29(d,J=8.2Hz,2H),3.85(s,3H),3.68(s,2H),1.76(s,2H).

[0163] Synthesis of 1-[4-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methanamine (D2) [ka] To a solution of 4-bromo-2-methyl-2H-1,2,3-triazole (3.23 g, 19.9 mmol) in 1,4-dioxane (40 ml), 4-N-(Boc)aminomethylphenylboronic acid (5.24 g, 20.9 mmol), water (4.0 ml), and potassium bicarbonate (4.0 g, 40.0 mmol) were added, and the resulting suspension was flushed with argon. Bis(triphenylphosphine)palladium(II) chloride (710 mg, 1.01 mmol) was added under argon. The mixture was heated to 80 °C and stirred at this temperature for 18 hours. Once the reaction mixture reached room temperature, it was treated with water and dichloromethane. The organic phase was separated, and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were dried over sodium sulfate and evaporated. The residue was chromatographed on a silica gel column using cyclohexane / ethyl acetate as eluent to give tert-butyl N-{[4-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methyl}carbamate as a white crystalline solid; UPLC / MS 0.739 min, [M-BocNH2] + 172. 1 H NMR(400MHz,DMSO-d6)δ8.17(s,1H),7.77(d,J=8.1Hz,2H),7.38(t,J=6.2Hz ,1H),7.31(d,J=8.0Hz,2H),4.18(s,3H),4.15(d,J=6.2Hz,2H),1.40(s,9H).

[0164] tert-Butyl N-{[4-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methyl}carbamate (3.2 g, 11.1 mmol) is dissolved in a 4N solution of hydrogen chloride in dioxane (75 ml), and the mixture is stirred at room temperature for 18 hours. The resulting precipitate is filtered off and washed with dichloromethane. The residue is treated with aqueous 1N sodium hydroxide until a basic pH value of 14 is reached. The solid is filtered off and washed with water. The residue is taken up in acetonitrile and filtered. The filtrate is evaporated and dried under vacuum to give 1-[4-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methanamine as a white crystalline solid; UPLC / MS 0.302 min, [M-NH2] + 172. 1 H NMR (500 MHz, DMSO-d) δ 8.16 (s, 1H), 7.75 (d, J = 8.2 Hz, 2H), 7.51-7.02 (m, 2H), 4.18 (s, 3H), 3.72 (s, 2H), NH peak not visible.

[0165] 4-(5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-benzylamine (D3) [ka] This compound was prepared similarly to D1; off-white solid; HPLC / MS (A) 0.93 min, [M+H] + 214.

[0166] 1-{4-[1-(2-methoxyethyl)-1H-pyrazol-4-yl]phenyl}methanamine (D4) [ka] This compound is prepared similarly to D2; yellow solid; HPLC / MS [M+H] + 215.

[0167] 1-[4-(1-methyl-1H-imidazol-4-yl)phenyl]methanamine (D5) [ka] This compound is prepared similarly to D2; yellow solid; HPLC / MS [M+H] + 188.

[0168] 1-{4-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]phenyl}methanamine (D6) [ka] This compound is prepared similarly to D2; yellow solid; HPLC / MS [M+H] + 228.

[0169] 1-(4-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}phenyl)methanamine (D7) [ka] This compound is prepared similarly to D2; yellow solid; HPLC / MS [M+H] + 287.

[0170] 1-(4-{1-[2-(pyrrolidin-1-yl)ethyl]-1H-pyrazol-4-yl}phenyl)methanamine (D8) [ka] This compound is prepared similarly to D2; yellow solid; HPLC / MS [M+H] + 271.

[0171] 1-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]methanamine (D9) [ka] This compound is prepared similarly to D2; yellow solid; HPLC / MS [M+H] + 188.

[0172] 1-[3-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]methanamine (D10) [ka] This compound was prepared similarly to D1; off-white solid; UPLC / MS 0.315 min, [M-NH2] + 189.

[0173] 2-{4-[4-(aminomethyl)phenyl]-1H-pyrazol-1-yl}ethan-1-ol (D11) [ka] This compound was prepared similarly to D2; yellow solid; HPLC / MS [M-NH2] + 201.

[0174] 1-[4-(1-methyl-1H-1,2,3-triazol-4-yl)phenyl]methanamine (D12) [ka] This compound is prepared similarly to D2; yellow solid; HPLC / MS [M+H] + 189.

[0175] Synthesis of 1-{4-[1-(oxetan-3-yl)-1H-pyrazol-4-yl]phenyl}methanamine (D13) [ka] To a solution of tert-butyl N-({4-[1-(oxetan-3-yl)-1H-pyrazol-4-yl]phenyl}methyl)carbamate (168 mg, 0.51 mmol) in dichloromethane (5 mL), prepared similarly to the first reaction step involving intermediate D1, trifluoroacetic acid (393 μL, 5.1 mmol) is added and the mixture is stirred at room temperature for 3 hours. The reaction mixture is treated with saturated aqueous sodium carbonate solution. The organic phase is separated and evaporated to give 1-{4-[1-(oxetan-3-yl)-1H-pyrazol-4-yl]phenyl}methanamine as a pale yellow solid; UPLC / MS 0.307 min, [M-NH2] + 213.

[0176] 1-[4-(4-methoxypyrimidin-2-yl)phenyl]methanamine (D14) [ka] This compound was prepared similarly to D2; off-white crystalline solid; HPLC / MS (A) 0.89 min, [M+H] + 216. 1 H NMR(500MHz,DMSO-d6)δ8.63(d,J=5.2Hz,1H),8.14(d,J=8.3Hz,2H),7.68(d, J=5.2Hz,1H),7.50(d,J=8.1Hz,2H),3.99(s,3H),3.79(s,2H),1.90(bs,2H).

[0177] 4-[4-(aminomethyl)phenyl]-1-methyl-1H-pyrazol-3-amine (D15) [ka] This compound is prepared similarly to D2; yellow solid; HPLC / MS [M+H] + 203.

[0178] 6-{7-Methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[5-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]methyl}pyrimidin-4-amine (D16) [ka] This compound was prepared similarly to D1; off-white solid; HPLC / MS (A) 0.84 min, [M-NH2] + 177. 1 H NMR(400MHz,DMSO-d6)δ7.92(d,J=0.7Hz,1H),7.62(d,J=0.8Hz,1H),6.94(d,J=3.5H z,1H),6.80(dt,J=3.5,1.0Hz,1H),3.84(d,J=1.1Hz,2H),3.83(s,3H),1.89(bs,2H).

[0179] 1-[4-(2-methyl-2H-1,2,3,4-tetrazol-5-yl)phenyl]methanamine (D17) [ka] This compound was prepared similarly to D2; yellow solid; UPLC / MS 0.294 min, [M-NH 2- N2] + 145.

[0180] Synthesis of 1-(4-{8-oxa-3-azabicyclo[3.2.1]octan-3-yl}phenyl)methanamine (D18) [ka] To a stirred solution of 4-fluorobenzonitrile (474 ​​mg, 3.92 mmol) and 8-oxa-3-azabicyclo[3.2.1]octane (443 mg, 3.92 mmol) in DMF (8 mL) is added cesium carbonate (2.55 g, 7.84 mmol). The resulting mixture is stirred at 80 °C for 16 h. The resulting mixture is filtered, the filter cake is washed with methanol, and the filtrate is concentrated under reduced pressure. The residue is purified by silica gel column chromatography eluting with PE / EtOAc (1:1) to give 4-[8-oxa-3-azabicyclo[3.2.1]octan-3-yl]benzonitrile as a white solid; HPLC / MS [M+H] + 215.

[0181] To a stirred solution of 4-[8-oxa-3-azabicyclo[3.2.1]octan-3-yl]benzonitrile (165 mg, 0.77 mmol) in THF (8 mL) is added lithium aluminum hydride (116 mg, 3.06 mmol) under a nitrogen atmosphere at 0°C. The resulting mixture is stirred at 25°C under a nitrogen atmosphere for 3 hours. The reaction is quenched at 0°C by the addition of water (10 mL). The aqueous layer is extracted with ethyl acetate (3 x 10 mL). The organic phase is evaporated under reduced pressure to give 1-(4-[8-oxa-3-azabicyclo[3.2.1]octan-3-yl]phenyl)methanamine as a white solid; HPLC / MS [M-NH2] + 202.

[0182] 1-[4-(1-methyl-1H-imidazol-5-yl)phenyl]methanamine (D19) [ka] This compound was prepared similarly to D1; orange-red resin; UPLC / MS 0.113 min, [M+H] + 188. 1H NMR (400 MHz, DMSO-d) δ 7.67 (d, J = 1.3 Hz, 1H), 7.41 (s, 4H), 7.00 (d, J = 1.2 Hz, 1H), 3.75 (s, 2H), 3.66 (s, 3H), NH peak not visible.

[0183] 1-[4-(6-methylpyridazin-3-yl)phenyl]methanamine (D20) [ka] This compound was prepared similarly to D2; off-white solid; UPLC / MS 0.288 min, [M+H] + 200.

[0184] 1-[4-(6-methylpyridazin-3-yl)phenyl]methanamine (D21) [ka] This compound was prepared similarly to D2; off-white powder; UPLC / MS 0.299 min, [M-NH2] + 183.

[0185] Synthesis of 1-[4-(2-methyl-1,3-oxazol-4-yl)phenyl]methanamine (D22) [ka] To a solution of 4-(2-methyl-1,3-oxazol-4-yl)benzonitrile (369 mg, 2.00 mmol) in methanol (15 ml) is added a 20% solution of ammonia in methanol (15 ml) and wet Raney-nickel (300 mg). The mixture is hydrogenated at 5 bar pressure and 60°C. The catalyst is filtered off and the filtrate is evaporated. The residue is triturated with tert-butyl methyl ether to give 1-[4-(2-methyl-1,3-oxazol-4-yl)phenyl]methanamine as an off-white powder; UPLC / MS 0.319 min, [M-NH2] + 202.

[0186] 5-[4-(aminomethyl)phenyl]-2-methylpyrimidin-4-amine (D23) [ka] This compound was prepared similarly to D2; off-white solid; UPLC / MS 0.118 min, [M+H] + 215.

[0187] Synthesis of 1-[5-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-2-yl]methanamine (D24) [ka] Yellow solid; HPLC / MS[M+H] + 186.

[0188] 1-[6-(2-methyl-2H-1,2,3-triazol-4-yl)pyridin-3-yl]methanamine (D25) [ka] This compound is prepared similarly to D24; white solid; HPLC / MS [M+H] + 190.

[0189] 1-{4-[2-(2-methoxyethyl)-2H-1,2,3-triazol-4-yl]phenyl}methanamine (D26) [ka] This compound was prepared similarly to D2; white solid; UPLC / MS 0.311 min, [M+H] + 233.

[0190] Synthesis of 1-[4-(1-cyclopropyl-1H-pyrazol-4-yl)phenyl]methanamine (D27) [ka] Light yellow oil; HPLC / MS[M+H] +214.

[0191] 1-[4-(3-methoxy-1-methyl-1H-pyrazol-4-yl)phenyl]methanamine (D28) [ka] This compound was prepared similarly to D2; pale yellow oil; HPLC / MS (B) 0.601 min, [M+H] + 218. 1 H NMR(400MHz,DMSO-d6)δ7.92(s,1H),7.51(d,J=8.2Hz,2H),7.31-7.18(m,2H),3.88(s,3H),3.71(s,3H),3.67(s,2H),2.00(bs,2H).

[0192] Synthesis of 1-[4-(1,3-oxazol-4-yl)phenyl]methanamine (D29) [ka] Yellow solid; HPLC / MS[M+H] + 171.

[0193] Synthesis of 1-[4-(3-methyl-1,2-oxazol-5-yl)phenyl]methanamine (D30) [ka] Yellow solid; HPLC / MS[M+H] + 189.

[0194] Synthesis of 1-[4-(5-methyl-1,3-oxazol-2-yl)phenyl]methanamine (D31) [ka] Yellow solid; HPLC / MS[M+H] + 189.

[0195] Synthesis of 1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]ethan-1-amine (D32) [ka] Brown solid; HPLC / MS[M+H] + 185.

[0196] Alkoxy-pyridylamine Synthesis of 4-(2-methoxy-ethoxy)-pyridin-2-ylamine (E1) [ka] Under nitrogen, a reaction flask is charged with diethylene glycol dimethyl ether (20 ml) and sodium hydride (60% suspension in paraffin oil, 915 mg, 23.0 mmol). A solution of ethylene glycol monomethyl ether (1.16 g, 15.3 mmol) in diethylene glycol dimethyl ether (10 ml) is added slowly at room temperature. The mixture is heated to 40°C and stirred at this temperature for 1 hour. 2-Amino-4-chloropyridine (980 mg, 7.62 mmol) is added. The mixture is heated to 160°C and stirred at this temperature for 20 hours. Once the reaction mixture has reached room temperature, the volume is reduced under vacuum. The residue is treated with water and dichloromethane. The organic phase is separated and the aqueous phase is extracted several times with dichloromethane. The combined organic phases are dried over sodium sulfate and evaporated. The residue is chromatographed on a silica gel column using ethyl acetate / methanol as eluent to give 4-(2-methoxy-ethoxy)-pyridin-2-ylamine as a brown solid; HPLC / MS (A) 0.79 min, [M+H] + 261.

[0197] 4-[(1,3-dimethoxypropan-2-yl)oxy]pyridin-2-amine (E2) [ka] Compound prepared similarly to E1; brown oil; HPLC / MS [M+H] + 213.

[0198] 4-(Oxan-4-yloxy)pyridin-2-amine (E3) [ka] Compound prepared similarly to E1; brown oil; HPLC / MS [M+H] + 195.

[0199] 4-[2-(morpholin-4-yl)ethoxy]pyridin-2-amine (E4) [ka] Compound prepared similarly to E1; off-white crystals; HPLC / MS (A) 0.273 min, [M+H] + 224. 1 H NMR(500MHz,DMSO-d6)δ7.70(d,J=5.8Hz,1H),6.12(dd,J=5.8,2.3Hz,1H),5.95(d,J=2.3Hz,1H) ,5.75(s,2H),4.03(t,J=5.8Hz,2H),3.60-3.53(m,4H),2.66(t,J=5.8Hz,2H),2.48-2.40(m,4H).

[0200] 4-(Oxolan-3-yloxy)pyridin-2-amine (E5) [ka] Compound prepared similarly to E1; brown oil; HPLC / MS [M+H] + 181.

[0201] 4-(Cyclopropylmethoxy)pyridin-2-amine (E6) [ka] Compound prepared similarly to E1; white solid; HPLC / MS [M+H] + 165.

[0202] 4-[2-(dimethylamino)ethoxy]pyridin-2-amine (E7) [ka] Compound prepared similarly to E1; yellow solid; HPLC / MS [M+H] + 182.

[0203] 4-[2-(pyrrolidin-1-yl)ethoxy]pyridin-2-amine (E8) [ka] Compound prepared similarly to E1; pale orange solid; UPLC / MS 0.113 min, [M+H] + 208. 1 H NMR(400MHz,DMSO-d6)δ7.70(d,J=5.8Hz,1H),6.11(dd,J=5.8,2.3Hz,1H),5.94(d,J=2.3Hz,1 H),5.76(s,2H),4.00(t,J=5.9Hz,2H),2.74(t,J=5.9Hz,2H),2.48(m,4H),1.73-1.61(m,4H).

[0204] 4-[2-(4-methylpiperazin-1-yl)ethoxy]pyridin-2-amine (E9) [ka] Compound prepared similarly to E1; light brown solid; HPLC / MS [M+H] + 237.

[0205] 4-[(1-methylpiperidin-4-yl)methoxy]pyridin-2-amine (E10) [ka] Compound prepared similarly to E1; white solid; HPLC / MS [M+H] + 222.

[0206] 4-[(1-methylpiperidin-4-yl)oxy]pyridin-2-amine (E11) [ka] Compound prepared similarly to E1; white solid; HPLC / MS [M+H] + 208.

[0207] Synthesis of 1-[(2-aminopyridin-4-yl)oxy]-2-methylpropan-2-ol (E12) [ka] To a solution of 2-aminopyridin-4-ol (200 mg, 1.73 mmol) in DMF (5 ml) was added 2,2-dimethyloxirane (393 mg, 5.18 mmol) and cesium carbonate (1.13 g, 3.46 mmol), and the resulting slurry was stirred at 40° C. for 18 hours. The solid was filtered off and washed with dichloromethane. The filtrate was evaporated and chromatographed on a silica gel column using dichloromethane / methanol as eluent to give 1-[(2-aminopyridin-4-yl)oxy]-2-methylpropan-2-ol as a white solid; HPLC / MS [M+H] + 183.

[0208] Synthesis of 2-[4-(oxetan-3-yl)piperazin-1-yl]ethan-1-ol (E13) [ka] To a solution of 1-(oxetan-3-yl)piperazine (284 mg, 1.73 mmol) in ethanol (5 ml), potassium carbonate (554 mg, 3.98 mmol) and 2-bromoethan-1-ol (524 mg, 3.98 mmol) are added, and the resulting slurry is stirred at 40° C. for 18 hours. The solid is filtered off and washed with dichloromethane. The filtrate is evaporated to give 2-[4-(oxetan-3-yl)piperazin-1-yl]ethan-1-ol as a white solid; HPLC / MS [M+H] + 187.

[0209] Subsequent synthetic steps are carried out analogously to the synthesis of E1 to provide 4-{2-[4-(oxetan-3-yl)piperazin-1-yl]ethoxy}pyridin-2-amine as a yellow oil; HPLC / MS [M+H] + 279.

[0210] 4-[3-(morpholin-4-yl)propoxy]pyridin-2-amine (E14) [ka] Compound prepared similarly to E1; yellow solid; HPLC / MS [M+H] + 238.

[0211] Synthesis of 4-[3-(pyrrolidin-1-yl)propoxy]pyridin-2-amine (E15) [ka] Under nitrogen, a reaction flask is charged with diethylene glycol dimethyl ether (75 ml) and sodium hydride (60% suspension in paraffin oil, 6.15 g, 154 mmol). 3-(Pyrrolidin-1-yl)propan-1-ol (10.2 g, 79.1 mmol) is slowly added and the mixture is stirred at room temperature for 1 hour. A solution of 2-amino-4-fluoropyridine (8.87 g, 79.1 mmol) in diethylene glycol dimethyl ether (60 ml) is added dropwise. The mixture is heated to 100°C and stirred at this temperature for 18 hours. Once the reaction mixture has cooled to room temperature, the volume is reduced under vacuum. The residue is taken up in acetonitrile. The solids are filtered off and the filtrate is evaporated. The residue is taken up in ethyl acetate and dried over sodium sulfate. The sodium sulfate is filtered off and the filtrate is cooled to 0°C. The crystalline solid that subsequently formed was filtered off, washed with cold ethyl acetate and dried under vacuum to give 4-[3-(pyrrolidin-1-yl)propoxy]pyridin-2-amine as a beige solid; UPLC / MS 0.116 min, [M+H] + 222. 1 H NMR(400MHz,DMSO-d6)δ7.70(d,J=5.8Hz,1H),6.10(dd,J=5.9,2.3Hz,1H),5.95(d,J=2.2Hz,1H),5.72(s, 2H),3.96(t,J=6.5Hz,2H),2.54-2.46(m,3H),2.48-2.36(m,4H),1.85(p,J=6.8Hz,2H),1.75-1.61(m,4H).

[0212] tert-Butyl 4-{[(2-aminopyridin-4-yl)oxy]methyl}piperidine-1-carboxylate (E16) [ka] Compound prepared similarly to E15; pale yellow solid; HPLC / MS (A) 1.24 min, [M+H] + 308. 1 H NMR(400MHz,DMSO-d6)δ7.69(d,J=5.8Hz,1H),6.10(dd,J=5.8,2.2Hz,1H),5.93(d,J=2.2Hz,1H),5.76(s,2H),4.10-3.92( m,4H),3.78(d,J=6.4Hz,2H),2.72(bs,4H),2.00-1.81(m,1H),1.71(dd,J=13.4,3.4Hz,4H),1.12(qd,J=12.5,4.3Hz,4H).

[0213] Synthesis of 4-{[1-(oxetan-3-yl)piperidin-4-yl]methoxy}pyridin-2-amine (E17) [ka] tert-Butyl 4-{[(2-aminopyridin-4-yl)oxy]methyl}piperidine-1-carboxylate (E16) (1.80 g, 4.98 mmol) is dissolved in a 4N solution of hydrogen chloride in dioxane (15 ml) and stirred at room temperature for 2 hours. A neutral pH is achieved by adding water and saturated sodium bicarbonate solution. The mixture is extracted with ethyl acetate. The organic phase is evaporated to give 4-[(piperidin-4-yl)methoxy]pyridin-2-amine as a yellow solid; HPLC / MS [M+H] + 208.

[0214] A solution of 4-[(piperidin-4-yl)methoxy]pyridin-2-amine (1.00 g, 4.68 mmol) and oxetan-3-one (355 mg, 4.68 mmol) in 1,2-dichloroethane (5 ml) is stirred at room temperature for 2 hours. 3.96 g (18.7 mmol) sodium triacetoxyborohydride is added, and the resulting mixture is stirred at room temperature for 16 hours. The reaction mixture is treated with water and dichloromethane. The organic phase is separated and evaporated. The residue is chromatographed on a silica gel column using dichloromethane / methanol as the eluent to give 4-{[1-(oxetan-3-yl)piperidin-4-yl]methoxy}pyridin-2-amine as a yellow solid; HPLC / MS [M+H] + 264.

[0215] 4-[2-(3,3-difluoropyrrolidin-1-yl)ethoxy]pyridin-2-amine (E18) [ka] Compound prepared similarly to E1; orange resin; UPLC / MS 0.164 min, [M+H] + 244. 1H NMR(500MHz,DMSO-d6)δ7.71(d,J=5.9Hz,1H),6.12(dd,J=5.9,2.3Hz,1H),5.95(d,J=2.3Hz,1H),5.74 (s,2H),4.02(t,J=5.6Hz,2H),2.96(t,J=13.5Hz,2H),2.87-2.72(m,4H),2.22(tt,J=15.3,7.0Hz,2H).

[0216] 4-[(1-methylpiperidin-4-yl)methoxy]pyridin-2-amine (E19) [ka] Compound prepared similarly to E15; yellow solid; HPLC / MS [M+H] + 222.

[0217] 4-{3-[(2-aminopyridin-4-yl)oxy]propyl}morpholin-3-one (E20) [ka] Compound prepared as in E15; colorless resin; UPLC / MS 0.288 min, [M+H] + 252. 1 H NMR(400MHz,DMSO-d6)δ7.70(d,J=5.9Hz,1H),6.10(dd,J=5.9,2.3Hz,1H),5.92(d,J=2.3Hz,1H),5.78(s,2H),4.01(s, 2H),3.93(t,J=6.3Hz,2H),3.82(dd,J=5.9,4.3Hz,2H),3.44(t,J=7.0Hz,2H),3.38-3.34(m,2H),1.93(p,J=6.6Hz,2H).

[0218] 4-[2-(3-fluoropyrrolidin-1-yl)ethoxy]pyridin-2-amine (E21) [ka] Compound prepared as in E15; colorless resin; UPLC / MS 0.112 min, [M+H] + 226. 1 H NMR(400MHz,DMSO-d6)δ7.70(d,J=5.9Hz,1H),6.12(dd,J=5.9,2.2Hz,1H),5.94(d,J =2.2Hz,1H),5.77(s,2H),5.18(dt,J=56.1,6.3Hz,1H),4.02(t,J=5.8Hz,2H),2.97- 2.80(m,2H),2.78(t,J=5.8Hz,2H),2.65(ddd,J=31.7,11.6,5.1Hz,1H),2.37(q,J=8 .0Hz,1H),2.11(ddq,J=27.8,14.0,7.0Hz,1H),1.85(ddt,J=29.4,14.3,7.2Hz,1H).

[0219] 4-[2-(3-fluoropyrrolidin-1-yl)ethoxy]pyridin-2-amine (E22) [ka] Compound prepared similarly to E15; yellow solid; HPLC / MS [M+H] + 250.

[0220] tert-Butyl 4-[(2-aminopyridin-4-yl)oxy]piperidine-1-carboxylate (E23) [ka] Compound prepared similarly to E15; off-white solid; HPLC / MS (A) 1.17 min, [M+H] + 294. 1H NMR(500MHz,DMSO-d6)δ7.71(d,J=5.9Hz,1H),6.14(dd,J=5.9,2.3Hz,1H),5.98(d,J=2.2Hz,1H),5.71(s,2H),4.51(tt,J=7.9,3.7 Hz,1H),3.64(ddd,J=13.4,6.6,4.3Hz,2H),3.23-3.01(m,2H),1.95-1.83(m,1H),1.50(ddt,J=17.1,8.6,3.9Hz,2H),1.40(s,9H).

[0221] 4-{2-[(2-aminopyridin-4-yl)oxy]ethyl}morpholin-3-one (E24) [ka] Compound prepared similarly to E15; off-white solid; HPLC / MS (A) 0.76 min, [M+H] + 238. 1 H NMR(500MHz,DMSO-d6)δ7.72(d,J=5.9Hz,1H),6.13(dd,J=5.8,2.3Hz,1H),5.96(d,J=2.3Hz,1H),5.75( s,2H),4.09(t,J=5.6Hz,2H),4.03(s,2H),3.87-3.74(m,2H),3.66(t,J=5.6Hz,2H),3.50-3.41(m,2H).

[0222] 4-[2-(oxan-2-yloxy)ethoxy]pyridin-2-amine (E25) [ka] Compound E1 prepared as above; brown oil; HPLC / MS (A) 1.82 min, [M+H] + 239. 1H NMR(500MHz,DMSO-d6)δ7.71(d,J=5.9Hz,1H),6.12(dd,J=5.9,2.3Hz,1H),5.9 5(d,J=2.3Hz,1H),5.72(s,2H),4.63(dd,J=4.4,3.1Hz,1H),4.07(td,J=4.1,1. 9Hz,1H),3.93-3.83(m,1H),3.80-3.73(m,1H),3.73-3.66(m,1H),3.48-3.38( m,1H),1.81-1.66(m,1H),1.62(tdd,J=9.9,4.8,2.7Hz,1H),1.53-1.38(m,5H).

[0223] 4-{2-[(2-aminopyridin-4-yl)oxy]ethyl}-1-methylpiperazin-2-one (E26) [ka] Compound prepared as in E15; brown resin; UPLC / MS 0.196 min, [M+H] + 251.

[0224] 4-[3-(4-methylpiperazin-1-yl)propoxy]pyridin-2-amine (E27) [ka] Compound prepared similarly to E15; white solid; UPLC / MS 0.115 min, [M+H] + 251.

[0225] Synthesis of 1-{2-[(2-aminopyridin-4-yl)oxy]ethyl}-4-(oxetan-3-yl)piperazin-2-one (E28) [ka] Light orange wax; HPLC / MS (A) 0.772 min, [M+H] + 293. 1H NMR(500MHz,DMSO-d6)δ7.72(d,J=5.8Hz,1H),6.13(dd,J=5.8,2.2Hz,1H),5.95(d,J=2.3Hz,1H),5.73(s,2H),4.53(t,J=6.6Hz,2H),4. 44(t,J=6.1Hz,2H),4.07(t,J=5.6Hz,2H),3.63(t,J=5.6Hz,2H),3.56-3.47(m,1H),3.44-3.40(m,2H),2.95(s,2H),2.65-2.53(m,2H).

[0226] tert-Butyl 3-{[(2-aminopyridin-4-yl)oxy]methyl}azetidine-1-carboxylate (E29) [ka] Compound prepared similarly to E15; off-white powder; UPLC / MS 0.407 min, [M+H] + 280.

[0227] 4-[2-(1-methyl-1H-imidazol-2-yl)ethoxy]pyridin-2-amine (E30) [ka] Compound prepared similarly to E15; yellow oil; HPLC / MS [M+H] + 219.

[0228] 4-[2-(azetidin-1-yl)ethoxy]pyridin-2-amine (E31) [ka] Compound prepared similarly to E15; yellow powder; UPLC / S 0.109 min, [M+2H] ++ / 297.5. 1H NMR(400MHz,DMSO-d6)δ7.70(d,J=5.8Hz,1H),6.08(dd,J=5.9,2.3Hz,1H),5.92(d,J=2.2Hz,1H),5. 72(s,2H),3.85(t,J=5.7Hz,2H),3.16(t,J=6.9Hz,4H),2.66(t,J=5.7Hz,2H),1.96(p,J=6.9Hz,2H).

[0229] 4-[3-(3,3-difluoropyrrolidin-1-yl)propoxy]pyridin-2-amine (E32) [ka] Compound prepared similarly to E15; beige solid; HPLC / MS (B) 0.165 min, [M+H] + 258. 1 H NMR(400MHz,DMSO-d6)δ7.69(d,J=5.8Hz,1H),6.09(dd,J=5.9,2.2Hz,1H),5.94(d,J=2.2Hz,1H),5.72(s,2H),3.95(t,J=6.4Hz) ,2H),2.87(t,J=13.5Hz,2H),2.69(t,J=7.0Hz,2H),2.53(t,J=7.1Hz,2H),2.22(tt,J=15.4,7.0Hz,2H),1.84(p,J=6.7Hz,2H).

[0230] Chloro-imidazopyridinyl-pyrimidine Synthesis of 3-(6-chloro-pyrimidin-4-yl)-7-methoxy-imidazo[1,2-a]pyridine (F1) [ka] To a solution of 7-methoxyimidazo[1,2-a]pyridine (3.70 g, 25 mmol) and 4-chloro-6-methylthiopyrimidine (6.02 g, 37.5 mmol) in a mixture of 1,4-dioxane (34 ml) and ethanol (17 ml) was added potassium carbonate (6.91 g, 50.0 mmol) and triphenylphosphine (2.1 g, 8.0 mmol). The suspension was flushed with argon, and palladium(II) acetate (898 mg, 4.00 mmol) was added. The mixture was stirred in a closed flask at 100°C for 18 hours. Once the reaction mixture had reached room temperature, 150 ml of water was added. The resulting precipitate was filtered off, washed with water, and dried. The residue is chromatographed on a silica gel column using methanol / dichloromethane as the eluent to give 7-methoxy-3-(6-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine as a light brown solid; HPLC / MS (A) 1.17 min, [M+H] + 273.

[0231] To a suspension of 7-methoxy-3-(6-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine (3.23 g, 11.9 mmol) in acetonitrile (31 ml) is added 37% hydrochloric acid, followed immediately by the addition of sulfuryl chloride (4.33 ml, 53.4 mmol). The reaction mixture is stirred at room temperature for 20 minutes and then poured into ice water (150 ml). The mixture is stirred at room temperature for 45 minutes. Saturated sodium bicarbonate solution is added until a pH value of 10-11 is reached. The resulting precipitate is filtered off and washed with water. The residue is crystallized from methanol to give 3-(6-chloro-pyrimidin-4-yl)-7-methoxy-imidazo[1,2-a]pyridine as an off-white solid; HPLC / MS (A) 1.13 min, [M+H] + 261. 1H NMR(500MHz,DMSO-d6)δ9.74(dd,J=7.7,0.7Hz,1H),8.97(d,J=1.1Hz,1H),8.67(s,1H),8. 20(d,J=1.1Hz,1H),7.21(dd,J=2.7,0.6Hz,1H),6.95(dd,J=7.7,2.7Hz,1H),3.91(s,3H).

[0232] Synthesis of 3-(6-chloro-pyrimidin-4-yl)-7-methoxy-imidazo[1,2-a]pyridine (F2) [ka] To a solution of 4-(2-methoxy-ethoxy)-pyridin-2-ylamine (879 mg, 5.23 mmol) in ethanol (20 ml) is added chloroacetaldehyde (ca. 50% solution in water, 903 mg, 5.75 mmol). The mixture is heated to 80° C. and stirred at this temperature for 18 hours. The volume of the reaction mixture is reduced in vacuo and the residue is treated with water and sodium bicarbonate solution. The organic phase is separated and the aqueous phase is extracted twice with dichloromethane. The organic phase is dried over sodium sulfate and evaporated. The residue is chromatographed on a silica gel column using dichloromethane / methanol as eluent to give 7-(2-methoxy-ethoxy)-imidazo[1,2-a]pyridine as a brown solid; UPLC-MS system: Waters Acquity H Class-SQD Method: Polar MS pos; Polar MS neg. Column: BEH C-18 2.1-50 1.7 μm; Column temperature: 40 °C Eluent A: Water + 0,1% HCOOH Eluent B: Acetonitrile + 0.08% HCOOH Flow: 0.9ml / min Gradient: 0 min 4% B, up to 100% B in 1 min 1. 100% B within 3 minutes 1.4 minutes to 4%B 4%B by 2 minutes Rt=0.556 min, [M+H] + 193.

[0233] The remaining steps are carried out analogously to the synthesis of 3-(6-chloro-pyrimidin-4-yl)-7-methoxy-imidazo[1,2-a]pyridine (F1); light brown solid; HPLC / MS (A) 1.14 min, [M+H] + 305. 1 H NMR(500MHz,DMSO-d6)δ9.75(d,J=7.7Hz,1H),8.98(s,1H),8.67(s,1H),8.21(s,1H),7.22(d, J=2.6Hz,1H),6.97(dd,J=7.6,2.7Hz,1H),4.36-4.16(m,2H),3.83-3.55(m,2H),3.33(s,3H).

[0234] Synthesis of 4-chloro-6-{imidazo[1,2-a]pyridin-3-yl}pyrimidine (F3) [ka] To a solution of 3-(tributylstannyl)imidazo[1,2-a]pyridine (11.0 g, 20.3 mmol) and 4,6-dichloropyrimidine (4.80 g, 30.6 mmol) in DMF (25 ml) under nitrogen, tetrakis(triphenylphosphane)palladium (1.64 g, 1.42 mmol) was added. The reaction mixture was stirred at 110° C. for 16 hours. Once the reaction mixture reached room temperature, it was concentrated under vacuum. The residue was chromatographed on a silica gel column using dichloromethane / methanol as eluent to give 4-chloro-6-{imidazo[1,2-a]pyridin-3-yl}pyrimidine as an off-white solid; HPLC / MS [M+H] + 231.

[0235] 3-(6-Methylsulfanyl-pyrimidin-4-yl)-7-trifluoromethyl-imidazo[1,2-a]pyridine (F4) [ka] This compound is prepared similarly to F1; off-white solid; HPLC / MS (A) 1.66 min, [M+H] + 299.

[0236] Ethoxy-ethenyl-pyrimidine 6-[(E)-2-Ethoxyethenyl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine (G1) [ka] To a suspension of 1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methanamine (10.8 g, 54.6 mmol) (D1) and 4,6-dichloropyrimidine (8.95 g, 60.1 mmol) in DMF (80 ml) is added trimethylamine (9.09 ml, 65.6 mmol) and the reaction mixture is stirred at 30° C. for 2 hours. The solid is filtered off and washed with DMF. The filtrate is evaporated under vacuum and the residue is treated with water and stirred at room temperature for 15 minutes. The precipitate is filtered off, washed with water and dried under vacuum. The residue is slurried in tert-butyl methyl ether and stirred for 10 minutes. The solid is filtered off, washed with tert-butyl methyl ether and dried under vacuum to give 6-chloro-N-{[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-methyl}-pyrimidin-4-amine as a beige solid; HPLC / MS (B) 0.682 min, [M+H] + 300. 1 H NMR(500MHz,DMSO-d6)δ8.28(s,1H),8.15(s,1H),8.08(d,J=0.8Hz,1H),7.81(d,J=0.8Hz ,1H),7.51(d,J=8.2Hz,2H),7.29(d,J=8.0Hz,2H),6.58(s,1H),4.52(s,2H),3.85(s,3H).

[0237] A suspension of 6-chloro-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]-methyl}-pyrimidin-4-amine (5.15 g, 17.2 mmol), (E)-1-ethoxyethene-2-boronic acid pinacol ester (5.11 g, 25.8 mmol), and tripotassium triphosphate (7.30 g, 34.4 mmol) in DMF is flushed with argon. Tetrakis(triphenylphosphine)-palladium (994 mg, 0.86 mmol) is added. The reaction mixture is heated to 100 °C and stirred at this temperature for 16 hours. When the reaction mixture reaches room temperature, it is treated with water. The precipitate is filtered off and dried. The filtrate is extracted several times with dichloromethane. The combined organic phases are dried over sodium sulfate and evaporated. The residue is combined with the previously obtained precipitate and chromatographed on a silica gel column using dichloromethane / methanol as the eluent. The product-containing fractions are combined and evaporated. The residue is triturated with tert-butyl methyl ether to give 6-[(E)-2-ethoxyethenyl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine as a beige crystalline solid; HPLC / MS (B) 0.696 min, [M+H] + 336. 1 H NMR(400MHz,DMSO-d6)δ8.21(d,J=1.0Hz,1H),8.07(d,J=0.8Hz,1H),7.80(d,J=0.8Hz,1H),7.72-7.57(m,2H),7.49(d,J=8.2Hz,2H),7.27(d, J=8.2Hz,2H),6.19(d,J=1.2Hz,1H),5.65(d,J=12.4Hz,1H),4.46(d,J=5.9Hz,2H),3.93(q,J=7.0Hz,2H),3.85(s,3H),1.25(t,J=7.0Hz,3H).

[0238] 6-[(E)-2-Ethoxyethenyl]-N-{[4-(1H-1,2,3-triazol-1-yl)phenyl]methyl}pyrimidin-4-amine (G2) [ka] Compound prepared similarly to G1; yellow solid; HPLC / MS [M+H] + 323.

[0239] 6-[(E)-2-Ethoxyethenyl]-N-{[4-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methyl}pyrimidin-4-amine (G3) [ka] Compound prepared similarly to G1; off-white crystalline solid; HPLC / MS (B) 0.708 min, [M+H] + 337. 1 H NMR(400MHz,DMSO-d6)δ8.21(s,1H),8.16(s,1H),7.77(d,J=8.3Hz,2H),7.69(t,J=6.2Hz,1H),7.64(d,J=12.4Hz,1H),7.37(d,J= 8.2Hz,2H),6.20(s,1H),5.66(d,J=12.4Hz,1H),4.51(d,J=6.0Hz,2H),4.18(s,3H),3.93(q,J=7.0Hz,2H),1.25(t,J=7.0Hz,3H).

[0240] 4-[(E)-2-Ethoxyethenyl]-6-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methoxy}pyrimidine (G4) [ka] Brown solid; HPLC / MS[M+H] + 337.

[0241] 6-[(E)-2-Ethoxyethenyl]-5-fluoro-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine (G5) [ka] Compound prepared similarly to G1; off-white powder; UPLC / MS 0.635 min, [M+H] + 354.

[0242] 6-[(E)-2-Ethoxyethenyl]-N-{1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]ethyl}pyrimidin-4-amine (G6) [ka] Compound G1 prepared from D32; brown oil; HPLC / MS [M+H] + 350.

[0243] Fluoroimidazopyridine 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine (H1) [ka] A suspension of 6-[(E)-2-ethoxyethenyl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine (G1) (335 mg, 1.00 mmol) in a mixture of 1,4-dioxane (4.5 ml) and water (1.5 ml) is cooled to 0° C., and N-bromosuccinimide (196 mg, 1.10 mmol) is added in portions over 15 minutes. After the final addition, the reaction mixture is stirred at 0° C. for 20 minutes. 2-Amino-4-fluoropyridine (118 mg, 1.00 mmol) is added. The reaction solution is heated to 60° C. and stirred at this temperature for 2 hours. When the reaction mixture reaches room temperature, it is poured into 1N aqueous NaOH solution (25 ml). The resulting mixture is stirred for several hours. The resulting solid material is filtered off, washed with water, dried, and chromatographed on a silica gel column using dichloromethane / methanol as eluent to give 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine as a pale yellow crystalline solid; HPLC / MS (B) 0.794 min, [M+H] + 400. 1 H NMR(500MHz,DMSO-d6)δ9.94-9.85(m,1H),8.55(s,1H),8.28(s,1H),8.07(s,1H),7.91(t,J=6.1Hz,1H),7.80(d,J=0.9Hz,1H),7.57(dd,J=9.8, 2.7Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.15(td,J=7.6,2.8Hz,1H),6.96(d,J=1.2Hz,1H),4.55(d,J=5.8Hz,2H),3.84(s,3H).

[0244] 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methyl}pyrimidin-4-amine (H2) [ka] Compound prepared similarly to H1; off-white powder; UPLC / MS 0.574 min, [M+H] + 401. 1 H NMR(700MHz,DMSO-d6)δ9.90(t,J=6.9Hz,1H),8.55(s,1H),8.29(s,1H),8.16(s,1H),7.95(t,J=6.2Hz,1H),7.79(d,J=8.2Hz,2H),7.5 6(dd,J=9.8,2.7Hz,1H),7.44(d,J=7.8Hz,2H),7.15(td,J=7.6,2.7Hz,1H),6.97(d,J=1.2Hz,1H),4.61(d,J=6.0Hz,2H),4.17(s,3H).

[0245] 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-1,2,3-triazol-4-yl)phenyl]methyl}pyrimidin-4-amine (H3) [ka] Compound H1 was prepared similarly; brown solid; HPLC / MS [M+H] + 401.

[0246] 6-{7-Fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(2-methyl-1,3-oxazol-4-yl)phenyl]methyl}pyrimidin-4-amine (H4) [ka] The compound is prepared from intermediate D22 in analogy to the alternative synthesis of H1; yellow solid; HPLC / MS [M+H] + 401.

[0247] 6-{7-Fluoroimidazo[1,2-a]pyridin-3-yl}-N-{1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]ethyl}pyrimidin-4-amine (H5) [ka] Compound H1 is prepared from G6 in analogy with H1; brown oil; HPLC / MS [M+H] + 414.

[0248] 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1,3-oxazol-4-yl)phenyl]methyl}pyrimidin-4-amine (H6) [ka] The compound is prepared from intermediate D29 in analogy to the alternative synthesis of H1; brown solid; HPLC / MS [M+H] + 387.

[0249] 6-{7-Fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(trifluoromethoxy)phenyl]methyl}pyrimidin-4-amine (H7) [ka] The compound is prepared from [4-(trifluoromethoxy)phenyl]methanamine in analogy to the alternative synthesis of H1; brown solid; HPLC / MS [M+H] + 404.

[0250] Alternative synthesis of fluoroimidazopyridines 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("H1") [ka] To a solution of 4,6-dichloropyrimidine (9.87 g, 66.3 mmol) and 2-[(E)-2-ethoxyethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (12.5 g, 63.1 mmol) in dioxane (90 ml) is added water (10 ml) and potassium phosphate tribasic (26.8 g, 126 mmol). Argon is passed through the mixture, and tetrakis(triphenylphosphine)-palladium (3.65 g, 3.16 mmol) is added. The mixture is heated to 80 °C and stirred at this temperature under argon for 3 hours. Once the reaction mixture has reached room temperature, it is concentrated in vacuo. The residue is partitioned between water and dichloromethane. The combined organic phases are dried over sodium sulfate and evaporated. The residue is chromatographed on a silica gel column using cyclohexane / ethyl acetate as eluent to give 4-chloro-6-[(E)-2-ethoxyethenyl]pyrimidine as an off-white crystalline solid; UPLC / MS 0.645 min, [M+H] + 185. 1 H NMR(400MHz,DMSO-d6)δ8.73(d,J=1.0Hz,1H),7.97(d,J=12.5Hz,1H),7.48(d,J= 1.0Hz,1H),5.89(d,J=12.5Hz,1H),4.05(q,J=7.0Hz,3H),1.29(t,J=7.0Hz,4H).

[0251] To a solution of 4-chloro-6-[(E)-2-ethoxyethenyl]pyrimidine (9.70 g, 52.5 mmol) in dioxane (375 ml) is added water (125 ml) and N-bromosuccinimide (8.88 g, 49.9 mmol). The mixture is stirred at room temperature for 1 hour. Then 4-fluoropyridin-2-amine (7.07 g, 63.1 mmol) is added. The reaction mixture is heated to 60° C. and stirred at this temperature for 2 hours. When the reaction mixture reaches room temperature, saturated sodium carbonate solution is added to bring the pH to 9. The mixture is concentrated under vacuum. The solid is filtered off, washed with water, and dried under vacuum. Trituration of the residue with a small amount of acetonitrile and a small amount of tert-butyl methyl ether afforded 4-chloro-6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}pyrimidine as a brown powder; UPLC / MS 0.577 min, [M+H] + 249. 1 H NMR(400MHz,DMSO-d6)δ9.96(ddd,J=7.8,6.0,0.8Hz,1H),9.05(d,J=1.1Hz,1H),8.81(s, 1H),8.32(d,J=1.2Hz,1H),7.73(ddd,J=9.7,2.8,0.7Hz,1H),7.32(td,J=7.6,2.8Hz,1H).

[0252] To a solution of 4-chloro-6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}pyrimidine (497 mg, 2.00 mmol) and 1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methanamine (D1, 497 mg, 2.00 mmol) in N,N-dimethylacetamide (4 ml) was added potassium carbonate (553 mg, 4.00 mmol), and the resulting mixture was heated at 80° C. for 16 hours. When the reaction mixture reached room temperature, water was added. The resulting precipitate was filtered off, washed with water, and dried under vacuum. The residue is chromatographed on a silica gel column using dichloromethane / methanol as eluent to give 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine as a pale yellow crystalline solid; HPLC / MS (B) 0.794 min, [M+H] + 400.

[0253] Example 1 Synthesis of [6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A1") [ka] To a solution of 4-chloro-6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}pyrimidine (F1) (75.6 mg, 0.29 mmol) and 1-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methanamine (D1) (56 mg, 0.30 mmol) in dimethyl sulfoxide (1.3 ml), potassium carbonate (81 mg, 0.59 mmol) and potassium iodide (5.0 mg, 30 μmol) were added. The mixture was heated to 100 °C and stirred at this temperature for 18 hours; once the reaction mixture reached room temperature, it was treated with excess water. The resulting precipitate was filtered off and washed with water. The residue is chromatographed on a silica gel column using methanol / dichloromethane as the eluent to give [6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine as a pale yellow powder; HPLC / MS (A) 1.23 min, [M+H] + 412. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(s,1H),7.84(t,J=6.4Hz,1H),7.81(d,J=0.8Hz,1H),7.51(d,J=8.2Hz, 2H),7.34(d,J=8.0Hz,2H),7.08(d,J=2.6Hz,1H),6.89(d,J=1.3Hz,1H),6. 80(dd,J=7.7,2.7Hz,1H),4.54(d,J=6.1Hz,2H),3.87(s,3H),3.84(s,3H).

[0254] The following compounds are prepared analogously: N-({[1,1'-biphenyl]-4-yl}methyl)-6-[7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine ("A2") [ka] From F2; Light brown powder; HPLC / MS (A) 1.99 min, [M+H] +452. 1 H NMR(500MHz,DMSO-d6)δ9.71(d,J=7.7Hz,1H),8.53(s,1H),8.17(s,1H),7.94(t,J=6.2Hz,1H),7.69-7.56(m,4H),7.45(t,J=7.7Hz,4H),7.40-7.3 1(m,1H),7.10(d,J=2.6Hz,1H),6.92(d,J=1.3Hz,1H),6.83(dd,J=7.7,2. 6Hz,1H),4.62(s,2H),4.28-4.19(m,2H),3.78-3.68(m,2H),3.33(s,3H).

[0255] N-({[1,1'-biphenyl]-4-yl}methyl)-6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A3") [ka] From F1; Off-white crystals; HPLC / MS (A) 1.55 min, [M+H] + 408. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.52(s,1H),8.16(s,1H),7.91(t,J=6.2Hz,1H),7.69-7.61(m,5H),7.52-7.40(m,7H) ),7.40-7.28(m,2H),7.08(d,J=2.6Hz,1H),6.91(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.7Hz,1H),4.61(d,J=6.0Hz,2H),3.87(s,3H).

[0256] 6-[7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A4") [ka] From D1 and F2; pale yellow solid; HPLC / MS (A) 1.30 min, [M+H]+ 456. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0. 8Hz,1H),7.84(t,J=6.3Hz,1H),7.81(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J =7.9Hz,2H),7.09(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.82(dd,J=7.7,2.6Hz,1H), 4.54(d,J=6.0Hz,2H),4.29-4.17(m,2H),3.84(s,3H),3.73-3.67(m,2H),3.32(s,3H).

[0257] 6-[7-(2-メトキシエトキシ)イミダゾ[1,2-a]ピリジン-3-イル]-N- {[4-(ピリジン-3-イル)フェニル]メチル}ピリミジン-4-アミン(「A5」)

change

[0258] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[4-(pyridin-3-yl)phenyl]methyl}pyrimidin-4-amine ("A6") [ka] From F1; Off-white solid; HPLC / MS (A) 1.06 min, [M+H] + 409. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.87(dd,J=2.5,0.9Hz,1H),8.55(dd, J=4.8,1.6Hz,1H),8.52(s,1H),8.16(s,1H),8.05(ddd,J=7.9,2.5,1.7Hz,1H),7.93 (t,J=6.2Hz,1H),7.70(d,J=8.2Hz,2H),7.56-7.43(m,3H),7.08(d,J=2.6Hz,1H),6. 92(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.62(d,J=5.9Hz,2H),3.87(s,3H).

[0259] 6-[7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl]-N-{[4-(1-methyl-1H-pyrazol-3-yl)phenyl]methyl}pyrimidin-4-amine ("A7") [ka] (from F2); pale yellow solid; HPLC / MS (A) 1.06 min, [M+H] + 456. 1H NMR(500MHz,DMSO-d6)δ9.76-9.63(m,1H),8.51(s,1H),8.14(s,1H),7.87(t,J=6.1H z,1H),7.74(d,J=8.3Hz,2H),7.69(d,J=2.3Hz,1H),7.37(d,J=7.8Hz,2H),7.14-7.0 8(m,1H),6.90(d,J=1.3Hz,1H),6.82(dd,J=7.7,2.6Hz,1H),6.64(d,J=2.2Hz,1H),4 .57(d,J=5.9Hz,2H),4.32-4.16(m,2H),3.86(s,3H),3.77-3.64(m,2H),3.33(s,3H).

[0260] (6-Imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-(4-imidazol-1-yl-benzyl)-amine ("A8") [ka] From F3; Off-white solid; HPLC / MS [M+H] + 368.

[0261] (6-Imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-(4-pyrazol-1-yl-benzyl)-amine ("A9") [ka] From F3; Off-white solid; mp217~219℃; HPLC / MS[M+H] + 368. 1 H NMR(400MHz,DMSO-d6,):δ9.86(d,J=7.0Hz,1H),8.57(s,1H),8.46(d,J=2.5Hz,1H),8.32(s,1H),8.01(m,1H),7.85-7.77( m,2H),7.75-7.68(m,2H),7.49(d,J=8.1Hz,2H),7.42(m,1H),7.10(m,1H),7.00(d,J=1.3Hz,1H),6.53(m,1H),4.62(s,2H).

[0262] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-[7-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine ("A10") [ka] From F4 and D1; white solid; HPLC / MS (A) 1.64 min, [M+H] + 450. 1 H NMR(400MHz,DMSO-d6)δ10.01(d,J=7.4Hz,1H),8.60(s,1H),8.49(s,1H),8.19(s,1H),8.08(s,1H),8.02(t,J=6.1H) z,1H),7.81(s,1H),7.52(d,J=8.2Hz,2H),7.41-7.32(m,3H),7.05(d,J=1.3Hz,1H),4.60-4.52(m,2H),3.85(s,3H).

[0263] 6-[7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl]-N-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}pyrimidin-4-amine ("A11") [ka] From F2; Off-white powder; HPLC / MS (A) 1.02 min, [M+H] + 457. 1H NMR(400MHz,DMSO-d6)δ9.71(d,J=7.8Hz,1H),8.56-8.49(m,2H),8.22(s,1H),8.19( s,1H),7.94(d,J=0.7Hz,1H),7.88(t,J=6.1Hz,1H),7.73(dd,J=8.2,2.2Hz,1H),7.59 (dd,J=8.1,0.9Hz,1H),7.10(d,J=2.6Hz,1H),6.91(d,J=1.3Hz,1H),6.83(dd,J=7.7, 2.6Hz,1H),4.55(d,J=6.0Hz,2H),4.28-4.16(m,2H),3.87(s,3H),3.78-3.64(m,2H).

[0264] 1-(4-{[(6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}pyrimidin-4-yl)amino]methyl}phenyl)piperidin-2-one ("A12") [ka] From F1; Light brown powder; HPLC / MS (A) 1.18 min, [M+H] + 429. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),7. 87(t,J=6.1Hz,1H),7.35(d,J=8.1Hz,2H),7.27-7.16(m,2H),7.08(d,J=2.6 Hz,1H),6.90(d,J=1.3Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.61-4.46(m,2H ),3.87(s,3H),3.63-3.49(m,2H),2.36(t,J=6.3Hz,2H),1.89-1.77(m,4H).

[0265] 4-{[(6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}pyrimidin-4-yl)amino]methyl}-N,N-dimethylbenzamide ("A13") [ka] From F1; Off-white solid; HPLC / MS (A) 1.19 min, [M+H] + 403. 1 H NMR(400MHz,DMSO-d6)δ9.79(d,J=7.6Hz,1H),8.59(s,1H),8.20(t,J=6.2Hz,1H),7.45-7.31(m,4H),7.26(d ,J=2.6Hz,1H),7.15(dd,J=7.7,2.6Hz,1H),7.00(s,1H),4.63(s,2H),3.98(s,3H),2.96(s,3H),2.90(s,3H).

[0266] (6-Imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-3-yl)-benzyl]-amine ("A14") [ka] From F3; White solid; mp 165-166°C; HPLC / MS [M+H] + 382. 1 H NMR(300MHz,DMSO-d6)δ9.83(d,J=7.0Hz,1H),8.54(s,1H),8.28(s,1H),7.99-7.92(m,1H),7.86-7.66(m,5H),7.37( dd,J=7.5,5.0Hz,2H),7.07(t,J=6.8Hz,1H),6.96(d,J=1.3Hz,1H),6.63(d,J=2.3Hz,1H),4.57(s,2H),3.84(s,3H).

[0267] [4-(4,5-Dihydro-1H-imidazol-2-yl)-benzyl]-(6-imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-amine ("A15") [ka] From F3; White solid; HPLC / MS [M+H] + 370.

[0268] 6-[7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl]-N-{[4-(1H-1,2,3-triazol-1-yl)phenyl]methyl}pyrimidin-4-amine ("A16") [ka] From F2; pale yellow solid; HPLC / MS (A) 1.17 min, [M+H] + 443. 1 H NMR(400MHz,DMSO-d6)δ9.71(d,J=7.7Hz,1H),8.79(d,J=1.3Hz,1H),8.52(s,1H) ,8.18(s,1H),8.00(t,J=6.2Hz,1H),7.96(d,J=1.1Hz,1H),7.92-7.70(m,2H),7.6 6-7.51(m,2H),7.10(d,J=2.6Hz,1H),6.93(d,J=1.3Hz,1H),6.83(dd,J=7.8,2.6 Hz,1H),4.64(d,J=5.9Hz,2H),4.32-4.14(m,2H),3.87-3.51(m,2H),3.32(s,3H).

[0269] 6-[7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl]-N-[(4-{4H,5H,6H-pyrrolo[1,2-b]pyrazol-3-yl}phenyl)methyl]pyrimidin-4-amine ("A17") [ka] From F2 and D3; pale yellow solid; HPLC / MS (A) 1.29 min, [M+H] + 482. 1H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.16(s,1H),7.89(t,J= 6.2Hz,1H),7.84(s,1H),7.52-7.43(m,2H),7.35(d,J=7.8Hz,2H),7.10(d,J=2.6Hz ,1H),6.89(d,J=1.3Hz,1H),6.83(dd,J=7.7,2.6Hz,1H),4.54(s,2H),4.24-4.18(m ,2H),4.07(t,J=7.3Hz,2H),3.76-3.61(m,2H),3.32(s,3H),3.04(t,J=7.3Hz,2H).

[0270] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1H-1,2,3-triazol-1-yl)phenyl]methyl}pyrimidin-4-amine ("A18") [ka] From F1; Light brown solid; HPLC / MS (A) 1.18 min, [M+H] + 399. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.79(d,J=1.2Hz,1H),8.52(s,1H),8.18(s,1H),8.00(t,J=6.3Hz,1H),7.96(d,J=1.2Hz,1H),7. 87(d,J=8.5Hz,2H),7.58(d,J=8.1Hz,2H),7.09(d,J=2.6Hz,1H),6.93(d,J=1.3Hz,1H),6.81(dd,J=7.7,2.7Hz,1H),4.65(s,2H),3.87(s,3H).

[0271] {4-[1-(2-Methoxy-ethyl)-1H-pyrazol-4-yl]-benzyl}-[6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-amine ("A19") [ka] From F1 and D4; Off-white solid; mp 212-213°C; HPLC / MS [M+H] + 456. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.8Hz,1H),8.51(s,1H),8.12(s,1H),7. 86(s,1H),7.92-7.82(m,2H),7.53(d,J=8.2Hz,2H),7.34(d,J=8.0Hz,2H),7 .08(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.80(d,J=2.7Hz,1H),4.54(s, 2H),4.25(t,J=5.3Hz,2H),3.87(s,3H),3.70(t,J=5.3Hz,2H),3.24(s,3H).

[0272] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(1-methyl-1H-imidazol-4-yl)-benzyl]-amine ("A20") [ka] From F1 and D5; pale yellow solid; mp 234-235°C; HPLC / MS [M+H] + 412. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1 H),8.51(s,1 H),8.15(s,1 H),7.87(t,J=5.6Hz,1 H),7.69(d,J=8.4Hz,2 H),7.60(s,1 H),7.55(s,1 H),7.33(d,J=8.4Hz,2 H),7.08(d,J=2.4Hz,1 H),6.89(s,1 H),6.80(dd,J=7.6,2.4Hz,1 H),4.55(s,2 H),3.87(s,3 H),3.67(s,3 H).

[0273] [4-(1-cyclopropylmethyl-1H-pyrazol-4-yl)-benzyl]-[6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-amine ("A21") [ka] From F1 and D6; white solid; mp 248-249°C; HPLC / MS [M+H] + 452. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.6Hz,1 H),8.51(s,1 H),8.16(s,2 H),7.88(t,J=6.1Hz,1 H),7.83(s,1 H),7.53(d,J=8.4Hz,2 H),7.35(d,J=7.6Hz,2 H),7.08(d,J=2.4Hz,1 H),6.90(d,J=0.8Hz,1H),6.80(dd,J=6.4,2.8Hz,1H),4.54(s,2 H),3.96(d,J=7.2Hz,2 H),3.87(s,3 H),1.29-1.21(m,1 H),0.55-0.51(m,2 H),0.37-0.34(m,2 H).

[0274] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-{4-[1-(2-morpholin-4-yl-ethyl)-1H-pyrazol-4-yl]-benzyl}-amine ("A22") [ka] From F1 and D7; white solid; mp 217-218°C; HPLC / MS [M+H] + 511. 1H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(d,J=0.8Hz,1H),7.87(t ,J=6.1Hz,1H),7.83(d,J=0.8Hz,1H),7.52(d,J=8.2Hz,2H),7.35(d,J=7.8Hz,2H),7.08(d ,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.7Hz,1H),4.54(s,2H),4.22(t,J =6.6Hz,2H),3.87(s,3H),3.57-3.50(m,4H),2.72(t,J=6.6Hz,2H),2.40(t,J=4.6Hz,4H).

[0275] [4-(1-ethyl-1H-pyrazol-4-yl)-benzyl]-[6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-amine ("A23") [ka] From F1; pale yellow solid; mp 251-252°C; HPLC / MS [M+H] + 426. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.15(d,J=0.8Hz ,2H),7.89(t,J=6.1Hz,1H),7.83(d,J=0.8Hz,1H),7.58-7.47(m,2H),7.35(d ,J=7.8Hz,2H),7.09(d,J=2.6Hz,1H),6.90(d,J=1.2Hz,1H),6.85-6.77(m,1 H),4.64-4.52(m,2H),4.18-4.08(m,2H),3.88(s,3H),1.39(t,J=7.3Hz,3H).

[0276] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-{4-[1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-4-yl]-benzyl}-amine ("A24") [ka] From F1 and D8; white solid; mp 203-205°C; HPLC / MS [M+H] + 495. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1 H),8.51(s,1H),8.14(d,J=0.9Hz,2 H),7.88(t,J=6.2Hz,1 H),7.83(d,J=0.8Hz,1 H),7.55-7.49(m,2 H),7.35-7.33(m,2 H),7.08(d,J=2.6Hz,1 H),6.89(d,J=1.2Hz,1 H),6.80(dd,J=7.7,2.7Hz,1 H),4.54(s,2 H),4.20(t,J=6.6Hz,2 H),3.87(s,3 H),2.83(t,J=6.6Hz,2 H),2.50-2.45(m,4 H), 1.66-1.62(m,4 H).

[0277] [4-(1,3-dimethyl-1H-pyrazol-4-yl)-benzyl]-[6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-amine ("A25") [ka] From F1; White solid; MP 264-265°C; HPLC / MS [M+H] + 426. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.15(s,1H),7.90(t,J=6.1Hz,1H),7.84(s,1H),7.37(s,4H),7. 09(d,J=2.7Hz,1H),6.90(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.56(s,2H),3.87(s,3H),3.76(s,3H),2.26(s,3H).

[0278] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]methyl}pyrimidin-4-amine ("A26") [ka] From F1; Off-white solid; HPLC / MS (A) 1.28 min, [M+H] + 414. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.52(d,J=1.1Hz,1H),8.16(s,1H),8.04-7.90(m,3H),7.53(d,J=7.9Hz,2H) ,7.08(d,J=2.7Hz,1H),6.92(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.65(d,J=6.1Hz,2H),3.87(s,3H),2.65(s,3H).

[0279] N-{[4-(1H-1,3-benzodiazol-1-yl)phenyl]methyl}-6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A27") [ka] From F1; Off-white solid; HPLC / MS (A) 1.21 min, [M+H] + 448. 1 H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.54(s,1H),8.52(s,1H),8.18(s,1H),7.99(t,J=6.2Hz,1H),7.79-7.72(m,1H),7.69-7.5 3(m,5H),7.37-7.25(m,2H),7.08(d,J=2.6Hz,1H),6.95(d,J=1.2Hz,1H),6.81(dd,J=7.7,2.7Hz,1H),4.68(d,J=5.7Hz,2H),3.88(s,3H).

[0280] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[3-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A28") [ka] From F1 and D9; pale yellow solid; mp 258-259°C; HPLC / MS [M+H] + 412. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.53(s,1H),8.18-8.13(m,1H),8 .11(s,1H),7.90(t,J=6.1Hz,1H),7.83(s,1H),7.58(s,1H),7.44(d,J=7.6,1.5H z,1H),7.32(t,J=7.6Hz,1H),7.20-7.17(m,1H),7.09(d,J=2.6Hz,1H),6.92(d, J=1.2Hz,1H),6.81(dd,J=7.7,2.6Hz,1H),4.60-4.52(m,2H),3.89-3.83(m,6H).

[0281] N-{[3-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A29") [ka] From F1 and D10; off-white powder; UPLC / MS 0.799 min, [M+H] + 430. 1H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(d,J=1.1Hz,1H),8.17(s,1H) ),8.08(d,J=2.2Hz,1H),7.89(t,J=6.2Hz,1H),7.84(dd,J=1.5,0.8Hz,1H),7.6 5(t,J=8.2Hz,1H),7.25-7.17(m,2H),7.08(d,J=2.6Hz,1H),6.91(d,J=1.2Hz,1 H),6.80(dd,J=7.7,2.7Hz,1H),4.57(d,J=5.9Hz,2H),3.88(s,3H),3.30(s,3H).

[0282] 2-[4-(4-{[6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-ylamino]-methyl}-phenyl)-pyrazol-1-yl]-ethanol ("A30") [ka] From F1 and D11; Off-white solid; mp 257-258°C; HPLC / MS [M+H] + 442. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.17-8.12(m,1H),8 .10(s,1H),7.91-7.82(m,2H),7.53(d,J=8.4Hz,2H),7.34(d,J=7.8Hz,2H),7.0 8(d,J=2.6Hz,1H),6.90(d,J=1.3Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.91(t,J =5.3Hz,1H),4.54(s,2H),4.14(t,J=5.7Hz,2H),3.87(s,3H),3.81-3.71(m,2H).

[0283] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(1-methyl-1H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A31") [ka] From F1 and D12; white solid; mp 254-255°C; HPLC / MS [M+H] + 413. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.47(s,1H),8.16(s,1H),7.92(t,J=6.2Hz,1H),7.83-7.76(m,2H),7.43 (d,J=7.8Hz,2H),7.08(d,J=2.6Hz,1H),6.93-6.91-6.90(m,1H),6.80(dd,J=7.7,2.6Hz,1H),4.59(s,2H),4.08(s,3H),3.87(s,3H).

[0284] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A32") [ka] (from F1 and D2); white solid; mp 253-254°C; HPLC / MS [M+H] + 413. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.18-8.17(m,2H),7.93(t,J=6.2Hz,1H),7.83-7.76(m,2H),7.44( d,J=7.8Hz,2H),7.08(d,J=2.6Hz,1H),6.93-6.88(m,1H),6.80(dd,J=7.7,2.7Hz,1H),4.60(s,2H),4.18(s,3H),3.87(s,3H).

[0285] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-({4-[1-(oxetan-3-yl)-1H-pyrazol-4-yl]phenyl}methyl)pyrimidin-4-amine ("A33") [ka] From F1 and D13; pale yellow powder; UPLC / MS 0.478 min, [M+H] + 454. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.31(d,J=0.8Hz,1H),8 .15(s,1H),7.98(d,J=0.8Hz,1H),7.85(t,J=6.1Hz,1H),7.56(d,J=8.3Hz,2H),7.3 6(d,J=7.8Hz,2H),7.08(d,J=2.7Hz,1H),6.89(d,J=1.3Hz,1H),6.80(dd,J=7.7,2. 6Hz,1H),5.62-5.50(m,1H),4.97-4.81(m,4H),4.55(d,J=6.1Hz,2H),3.87(s,3H).

[0286] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[4-(4-methoxypyrimidin-2-yl)phenyl]methyl}pyrimidin-4-amine ("A34") [ka] From F1 and D14; pale yellow solid; UPLC / MS 0.500 min, [M+H] + 441. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.64(d,J=5.2Hz,1H),8.52(d ,J=1.1Hz,1H),8.16(d,J=8.4Hz,2H),7.95(t,J=6.2Hz,1H),7.67(d,J=5.3H z,1H),7.52(d,J=8.0Hz,2H),7.08(d,J=2.6Hz,1H),6.92(d,J=1.3Hz,1H),6 .80(dd,J=7.7,2.6Hz,1H),4.65(d,J=6.0Hz,2H),3.98(s,4H),3.87(s,3H).

[0287] [4-(3-amino-1-methyl-1H-pyrazol-4-yl)-benzyl]-[6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-amine ("A35") [ka] From F1 and D15; white solid; mp 271-272°C; HPLC / MS [M+H] + 427. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.50(s,1H),8.17-8.13(m,1H),7.88(t,J=6.2Hz,1H),7.65(s,1H),7.42(d,J=8.0Hz,2H),7. 34-7.28(m,2H),7.07(d,J=2.6Hz,1H),6.91-6.86(m,1H),6.80(dd,J=7.7,2.6Hz,1H),4.59(s,2H),4.52(s,2H),3.87(s,3H),3.60(s,3H).

[0288] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[5-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]methyl}pyrimidin-4-amine ("A36") [ka] From F1 and D16; pale yellow solid; HPLC / MS (A) 1.24 min, [M+H] + 418. 1 H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.56(s,1H),8.16(s,1H),7.93(d,J=0.7Hz,1H),7.88(t,J=6.1Hz,1H),7.62(d,J=0.8Hz, 1H),7.08(d,J=2.6Hz,1H),7.01-6.94(m,4H),6.91(s,1H),6.81(dd,J=7.7,2.6Hz,1H),4.69(d,J=6.0Hz,2H),3.88(s,3H),3.81(s,3H).

[0289] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[4-(2-methyl-2H-1,2,3,4-tetrazol-5-yl)phenyl]methyl}pyrimidin-4-amine ("A37") [ka] From F1 and D17; yellow powder; UPLC / MS 0.476 min, [M+H] + 414. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.52(d,J=1.2Hz,1H),8.16(s,1H),8.02(d,J=8.2Hz,2H),7.93(t,J=6.2Hz,1H),7.54(d, J=7.9Hz,2H),7.08(d,J=2.6Hz,1H),6.92(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.65(d,J=6.1Hz,2H),4.41(s,3H),3.88(s,3H).

[0290] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-benzyl]-amine ("A38") [ka] From F1 and D18; yellow solid; mp 201-202°C; HPLC / MS [M+H] + 443. 1H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.8Hz,1H),8.49(s,1H),8.23-8.02(m,1H),7.77(t,J=6.2Hz,1H),7.29-7.16(m,2H),7.08(s,1 H),6.92-6.66(m,4H),4.51-4.27(m,4H),3.87(s,3H),3.43-3.35(m,1H),3.32-3.26(m,1H),2.79-2.69(m,2H),1.93-1.71(m,4H).

[0291] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-imidazol-5-yl)phenyl]methyl}pyrimidin-4-amine ("A39") [ka] From F1 and D19; yellow powder; UPLC / MS 0.342 min, ([M+2H] 2+ ) / 2 206.5. 1 H NMR(400MHz,DMSO-d6)δ9.80(s,1H),9.14(s,1H),8.60(s,1H),8.28(s,1H),7.83(d,J=1.5Hz,1H),7.67-7 .43(m,5H),7.28(d,J=2.6Hz,1H),7.26-7.12(m,1H),7.03(s,1H),4.68(s,2H),3.98(s,3H),3.82(s,3H).

[0292] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[4-(6-methylpyridazin-3-yl)phenyl]methyl}pyrimidin-4-amine ("A40") [ka] From F1 and D20; off-white resin; UPLC / MS 0.452 min, [M+H] + 424. 1H NMR(400MHz,DMSO-d6)δ8.73(s,1H),8.63(s,1H),8.37(t,J=6.2Hz,1H),8.14(d,J=8.8Hz,1H),8.11(d,J=8.3Hz,2H),7.69(d,J=8.8H) z,1H),7.52(d,J=7.8Hz,2H),7.32(d,J=2.6Hz,1H),7.26(dd,J=7.7,2.6Hz,1H),7.05(s,1H),4.70(bs,2H),4.02(s,3H),2.66(s,3H).

[0293] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[4-(2-methylpyrimidin-5-yl)phenyl]methyl}pyrimidin-4-amine ("A41") [ka] From F1 and D21; pale yellow powder; UPLC / MS 0.456 min, [M+H] + 424. 1 H NMR(400MHz,DMSO-d6)δ9.73(s,1H),9.00(s,2H),8.52(s,1H),8.23(s,1H),7.98(t,J=6.2Hz,1H),7.82-7.69(m,2 H),7.51(d,J=7.8Hz,2H),7.09(s,1H),6.92(s,1H),6.81(d,J=7.7Hz,1H),4.62(s,2H),3.87(s,3H),2.65(s,3H).

[0294] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[4-(2-methyl-1,3-oxazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A42") [ka] From F1 and D22; off-white powder; UPLC / MS 0.495 min, [M+H] + 495. 1H NMR(500MHz,DMSO-d6)δ8.51(s,1H),8.40(s,1H),8.14(s,1H),7.86(t,J=6.1Hz,1H),7.70(d,J=7.9Hz,2H),7.40(d,J=7. 9Hz,2H),7.07(d,J=2.6Hz,1H),6.90(s,1H),6.80(dd,J=7.7,2.6Hz,1H),4.58(d,J=6.1Hz,2H),3.87(s,2H),2.45(s,3H).

[0295] 5-(4-{[(6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}pyrimidin-4-yl)amino]methyl}phenyl)-2-methylpyrimidin-4-amine ("A43") [ka] From F1 and D23; Off-white solid; HPLC / MS (A) 0.95 min, [M+H] + 439. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.52(d,J=1.1Hz,1H),8.16(s ,1H),7.91(t,J=6.5Hz,1H),7.89(s,1H),7.45(d,J=7.9Hz,2H),7.38(s,1H), 7.36(d,J=4.8Hz,1H),7.09-7.06(m,1H),6.91(d,J=1.2Hz,1H),6.80(dd,J=7 .7,2.6Hz,1H),6.42(s,3H),4.61(d,J=5.9Hz,2H),3.88(s,3H),2.35(s,3H).

[0296] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[5-(2-methyl-2H-[1,2,3]triazol-4-yl)-pyridin-2-ylmethyl]-amine ("A44") [ka] From F1 and D24; white solid; mp 254-256°C; HPLC / MS [M+H]+ 414. 1 H NMR(300MHz,DMSO-d6)δ9.70(d,J=7.8Hz,1H),8.99(d,J=2.1Hz,1H),8.51(s,1H),8.31(s,1H),8.15(d,J=7.9Hz,2H),7.96(s,1H),7. 44(d,J=8.1Hz,1H),7.09(d,J=2.6Hz,1H),6.99(s,1H),6.81(dd,J=7.7,2.6Hz,1H),4.70(d,J=6.0Hz,2H),4.21(s,3H),3.87(s,3H).

[0297] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[6-(2-methyl-2H-[1,2,3]triazol-4-yl)-pyridin-3-ylmethyl]-amine ("A45") [ka] From F1 and D25; yellow solid; mp 260-261°C; HPLC / MS [M+H] + 414. 1 H NMR(300MHz,DMSO-d6)δ9.27(s,1H),8.86(s,1H),8.79(s,3H),8.59(s,1H),8.40(d,J=8.4Hz, 1H),7.43(d,J=2.6Hz,2H),7.28(dd,J=7.7,2.7Hz,1H),4.94(s,2H),4.27(s,3H),3.98(s,3H).

[0298] N-({4-[2-(2-methoxyethyl)-2H-1,2,3-triazol-4-yl]phenyl}methyl)-6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A46") [ka] From F1 and D26; Light brown solid; UPLC / MS 0.491 min, [M+H] + 457. 1 H NMR(500MHz,DMSO-d6)δ9.74-9.68(m,1H),8.52(d,J=1.2Hz,1H),8.19(s, 1H),8.16(s,1H),7.95-7.86(m,1H),7.80(d,J=8.2Hz,2H),7.46(d,J=7.9H z,2H),7.08(d,J=2.6Hz,1H),6.92(d,J=1.3Hz,1H),6.80(dd,J=7.7,2.7H z,1H),4.67-4.53(m,5H),3.88(s,3H),3.85(t,J=5.3Hz,2H),3.23(s,3H).

[0299] 6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methyl}pyrimidin-4-amine ("A47") [ka] From F1; beige powder; UPLC / MS 0.488 min, [M+H] + 414. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(d,J=1.1Hz,1H),8.16(s,1H),8.06(d,J=8.3Hz,2H),7.98(t,J=6.2Hz,1H),7.5 9(d,J=8.0Hz,2H),7.08(d,J=2.6Hz,1H),6.93(s,1H),6.80(dd,J=7.7,2.7Hz,1H),4.68(d,J=6.1Hz,2H),3.88(s,3H),2.40(s,3H).

[0300] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(2-methyl-oxazol-5-yl)-benzyl]-amine ("A48") [ka] From F1; White solid; mp 225-226°C; HPLC / MS [M+H] +413. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.25-8.13(m,1H),7.91(t,J=6.3Hz,1H),7.66-7.60(m,2H),7.4 9-7.40(m,3H),7.08(d,J=2.6Hz,1H),6.90(s,1H),6.80(dd,J=7.7,2.6Hz,1H),4.63-4.54(m,2H),3.87(s,3H),2.46(s,3H).

[0301] [4-(1-cyclopropyl-1H-pyrazol-4-yl)-benzyl]-[6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-amine ("A49") [ka] From F1 and D27; white solid; mp 261-262°C; HPLC / MS [M+H] + 438. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.8Hz,1H),8.51(s,1H),8.20-8.09(m,2H),7. 89-7.78(m,2H),7.56-7.50(m,2H),7.34(d,J=7.8Hz,2H),7.08(d,J=2.7Hz,1H),6 .89(d,J=1.3Hz,1H),6.80(dd,J=7.7,2.7Hz,1H),4.61-4.51(m,2H),3.87(s,3H), 3.72(tt,J=7.3,3.8Hz,1H),1.10-1.00(m,2H),0.96(ddd,J=7.7,6.4,4.4Hz,2H).

[0302] N-{[4-(3-methoxy-1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A50") [ka] From F1 and D28; Off-white solid; HPLC / MS (B) 0.753 min, [M+H] + 442. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.13(s,1H),7.92(s,1H),7.81(t,J=6.1Hz,1H),7.54(d,J=8.3Hz,2H),7.31(d ,J=7.9Hz,2H),7.07(d,J=2.6Hz,1H),6.88(d,J=1.2Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.52(d,J=6.0Hz,2H),3.87(s,6H),3.70(s,3H).

[0303] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-(4-oxazol-4-yl-benzyl)-amine ("A51") [ka] From F1 and D29; pale yellow solid; mp 268-269°C; HPLC / MS [M+H] + 399. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.57(d,J=1.0Hz,1H),8.50(d,J=1.1Hz,1H),8.42(d,J=1.0Hz,1H),8.14(s,1H),7.90(t,J=6.1Hz,1H), 7.79-7.70(m,2H),7.41(d,J=7.9Hz,2H),7.06(d,J=2.6Hz,1H),6.89(d,J= 1.3Hz,1H),6.78(dd,J=7.7,2.7Hz,1H),4.57(d,J=5.9Hz,2H),3.85(s,3H).

[0304] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(3-methyl-isoxazol-5-yl)-benzyl]-amine ("A52") [ka] From F1 and D30; pale yellow solid; mp 198-199°C; HPLC / MS [M+H] + 413. 1 H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.20-8.14(m,1H),7.95(t,J=6.2Hz,1H),7.79(d,J=8.1Hz,2H) ,7.49(d,J=7.9Hz,2H),7.08(d,J=2.6Hz,1H),6.91(s,1H),6.85-6.75(m,2H),4.66-4.58(m,2H),3.87(s,3H),2.27(s,3H).

[0305] [6-(7-Methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(5-methyl-oxazol-2-yl)-benzyl]-amine ("A53") [ka] From F1 and D31; yellow solid; mp 281-282°C; HPLC / MS [M+H] + 413. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(d,J=1.1Hz,1H),8.19-8.14(m,1H),7.95(t,J=6.2Hz,1H),7.92-7.86(m,2H),7.4 8(d,J=7.9Hz,2H),7.08(d,J=2.7Hz,1H),6.99-6.89(m,2H),6.80(dd,J=7.7,2.7Hz,1H),4.69-4.55(m,2H),3.87(s,3H),2.37(s,3H).

[0306] Example 2 Synthesis of 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("H1") [ka] A suspension of 6-[(E)-2-ethoxyethenyl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine (G1) (335 mg, 1.00 mmol) in a mixture of 1,4-dioxane (4.5 ml) and water (1.5 ml) was cooled to 0 °C, and N-bromosuccinimide (196 mg, 1.10 mmol) was added in portions over 15 minutes. After the final addition, the reaction mixture was stirred at 0 °C for 20 minutes. 2-Amino-4-fluoropyridine (118 mg, 1.00 mmol) was added. The reaction solution was heated to 60 °C and stirred at this temperature for 2 hours. Once the reaction mixture reached room temperature, it was poured into 1N aqueous NaOH solution (25 ml). The resulting mixture was stirred for several hours. The resulting solid material is filtered off, washed with water, dried, and chromatographed on a silica gel column using dichloromethane / methanol as eluent to give 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine as a pale yellow crystalline solid; HPLC / MS (B) 0.794 min, [M+H] + 400. 1 H NMR(500MHz,DMSO-d6)δ9.94-9.85(m,1H),8.55(s,1H),8.28(s,1H),8.07(s,1H),7.91(t,J=6.1Hz,1H),7.80(d,J=0.9Hz,1H),7.57(dd,J=9.8, 2.7Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.15(td,J=7.6,2.8Hz,1H),6.96(d,J=1.2Hz,1H),4.55(d,J=5.8Hz,2H),3.84(s,3H).

[0307] The following compounds are prepared analogously: {6-[7-(2-methoxy-1-methoxymethyl-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A54") [ka] From G1 and E2; yellow solid; mp 52-53°C; HPLC / MS [M+H] + 452. 1 H NMR(300MHz,DMSO-d6)δ9.80(s,1H),8.71(s,1H),8.60(s,1H),8.31(s,1H),8.08(s,1H),7.82(s,1H),7.55-7.44(m,3H) ,7.38-7.23(m,3H),7.02(s,1H),5.02(t,J=4.9Hz,1H),4.63-4.48(m,2H),3.85(s,3H),3.73-3.51(m,4H),3.27(s,6H).

[0308] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(tetrahydro-pyran-4-yloxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A55") [ka] From G1 and E3; white solid; mp 215-216°C; HPLC / MS [M+H] + 482. 1H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.8Hz,1H),8.59-8.41(m,1H),8.41-8.0 2(m,2H),7.95-7.85(m,1H),7.80(s,1H),7.50(d,J=7.9Hz,2H),7.30(m,2H) ,7.20(s,1H),6.97-6.71(m,2H),4.79-4.77(m,1H),4.62-4.48(m,2H),3.94 -3.80(m,5H),3.52(t,J=10.4Hz,2H),2.15-1.92(m,2H),1.71-1.51(m,2H).

[0309] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(2-morpholin-4-yl-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A56") [ka] From G1 and E4; Off-white solid; mp 220-221°C; HPLC / MS [M+H] + 511. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.6Hz,1H),8.49(s,1H),8.14(s,1H),8.07(s,1H) ),7.86(t,J=6.1Hz,1H),7.80(s,1H),7.50(d,J=7.9Hz,2H),7.32(d,J=7.9Hz,2H), 7.09(d,J=2.6Hz,1H),6.87(s,1H),6.84-6.75(m,1H),4.52(s,2H),4.19(t,J=5.5H z,2H),3.83(s,3H),3.57(t,J=4.7Hz,4H),2.72(t,J=5.5Hz,2H),2.51-2.42(s,4H).

[0310] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(tetrahydro-furan-3-yloxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A57") [ka] From G1 and E5; Off-white solid; mp 283-294°C; HPLC / MS [M+H] + 468. 1 H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.50(s,1H),8.15(s,1H),8.07( s,1H),7.87(t,J=6.0Hz,1H),7.80(s,1H),7.50(d,J=8.1Hz,2H),7.32(d,J=7.8 Hz,2H),7.07(d,J=2.6Hz,1H),6.88(s,1H),6.85-6.67(m,1H),5.22-5.15(m,1 H),4.62-4.51(m,2H),3.96-3.72(m,7H),2.39-2.21(m,1H),2.06-1.96(m,1H).

[0311] 6-[7-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-3-yl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A58") [ka] From G1 and E6: pale yellow solid; mp 236-237°C; HPLC / MS [M+H] + 452. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.49(s,1H),8.12(s,1H),8.07(s,1H), 7.86(t,J=6.1Hz,1H),7.80(s,1H),7.54-7.46(m,2H),7.32(d,J=7.9Hz,2H),7.00(d, J=2.6Hz,1H),6.87(d,J=1.2Hz,1H),6.81(dd,J=7.7,2.6Hz,1H),4.52(d,2H),3.92(d ,J=7.1Hz,2H),3.83(s,3H),1.31-1.19(m,1H),0.65-0.50(m,2H),0.42-0.28(m,2H).

[0312] 6-{7-[2-(dimethylamino)ethoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A59") [ka] From G1 and E7; Off-white solid; mp 235-236°C; HPLC / MS [M+H] + 469. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.49(s,1H),8.14(s,1H),8.07(s,1H) ,7.86(t,J=6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.50(d,J=8.2Hz,2H),7.32(d,J=7.9Hz ,2H),7.09(d,J=2.6Hz,1H),6.87(d,J=1.2Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.57 -4.49(m,2H),4.14(t,J=5.7Hz,2H),3.83(s,3H),2.65(t,J=5.6Hz,2H),2.21(s,6H).

[0313] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(2-pyrrolidin-1-yl-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A60") [ka] From G1 and E8; off-white solid; UPLC / MS 0.376 min, [M+H] + 495. 1H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(s,1H) ,7.84(t,J=6.2Hz,1H),7.81(s,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.0 9(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.81(dd,J=7.7,2.6Hz,1H),4.54(d,J=4.8H z,2H),4.19(t,J=5.5Hz,2H),3.84(s,3H),2.87(bs,2H),2.57(bs,4H),1.71(bs,4H).

[0314] (6-{7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A61") [ka] From G1 and E9; white solid; mp 200-201°C; HPLC / MS [M+H] + 524. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.49(s,1H),8.14(s,1H),8.07(s,1H),7.86(t, J=6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.50(d,J=8.2Hz,2H),7.32(d,J=7.9Hz,2H),7.08(d,J=2. 6Hz,1H),6.87(d,J=1.2Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.59-4.47(m,2H),4.16(t,J=5.6H z,2H),3.83(s,3H),2.71(t,J=5.6Hz,2H),2.57(s,2H),2.44(s,2H),2.30(s,4H),2.13(s,3H).

[0315] {6-[7-(1-methyl-piperidin-4-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A62") [ka] From G1 and E10; white solid; mp 238-239°C; HPLC / MS [M+H] + 509. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.49(s,1H),8.13(s,1H),8.07(s,1H),7.86(t,J=6.0H z,1H),7.80(d,J=0.8Hz,1H),7.50(d,J=8.2Hz,2H),7.32(d,J=7.9Hz,2H),7.05(d,J=2.5Hz,1H),6.87 (d,J=1.2Hz,1H),6.78(dd,J=7.7,2.6Hz,1H),4.55-4.49(m,2H),3.93(d,J=5.9Hz,2H),3.83(s,3H),2 .77(d,J=11.0Hz,2H),2.14(s,3H),1.86(t,J=11.5Hz,2H),1.73(d,J=11.7Hz,3H),1.40-1.25(m,2H).

[0316] {6-[7-(1-methyl-piperidin-4-yloxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A63") [ka] From G1 and E11; Off-white solid; mp 224-225°C; HPLC / MS [M+H] + 495. 1H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.49(s,1H),8.13(s,1H),8.07(s,1H),7.8 6(t,J=6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.50(d,J=8.2Hz,2H),7.32(d,J=7.8Hz,2H),7. 12(d,J=2.6Hz,1H),6.87(d,J=1.2Hz,1H),6.77(dd,J=7.7,2.6Hz,1H),4.70-4.46(m,3H) ,3.83(s,3H),2.65-2.54(m,2H),2.31-2.12(m,5H),2.08-1.88(m,2H),1.83-1.59(m,2H).

[0317] 2-Methyl-1-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxy)-propan-2-ol ("A64") [ka] From G1 and E12; Off-white solid; mp 229-230°C; HPLC / MS [M+H] + 480. 1 H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.50(s,1H),8.19-8.03(m,2H),7.91-7.77(m,2H),7.50(d,J=7.8Hz,2H),7.32( d,J=7.8Hz,2H),7.07-7.01(m,1H),6.88(s,1H),6.85-6.76(m,1H),4.71(s,1H),4.60-4.42(m,2H),3.83(s,5H),1.21(s,6H).

[0318] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-(6-{7-[2-(4-oxetan-3-yl-piperazin-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A65") [ka] From G1 and E13; yellow solid; mp 209-210°C; HPLC / MS [M+H] + 566. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.6Hz,1H),8.49(s,1H),8.16-8.05(m,2H),7.93-7.85(m,1H),7.80(d,J=0.8Hz,1H),7.50 (d,J=8.1Hz,2H),7.32(d,J=7.9Hz,2H),7.09(d,J=2.6Hz,1H),6.87(s,1H),6.79(dd,J=7.8,2.6Hz,1H),4.50(t,J=6.5Hz,4H)

[0319] [6-(7-methyl-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A66") [ka] From G1; Off-white solid; mp 229-230°C; HPLC / MS [M+H] + 396. 1 H NMR(300MHz,DMSO-d6)δ9.71(d,J=7.2Hz,1H),8.52(s,1H),8.20(s,1H),8.07(s,1H),7.90(t,J=6.1Hz,1H),7.80 (s,1H),7.55-7.44(m,3H),7.33(d,J=7.8Hz,2H),6.98-6.88(m,2H),4.59-4.46(m,2H),3.83(s,3H),2.38(s,3H).

[0320] (6-{7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-(4-[1,2,3]triazol-1-yl-benzyl)-amine ("A67") [ka] (From G2 and E9) White solid; mp 233-234°C; HPLC / MS [M+H] + 511. 1 H NMR (400MHz, methanol-d4) δ9.72(d,J=7.7Hz,1H),8.53(d,J=8.0,1.2Hz,2H),8.0 7(s,1H),7.90(s,1H),7.88-7.82(m,2H),7.62(d,J=8.3Hz,2H),7.00(d,J=2.6H z,1H),6.90(s,1H),6.80(dd,J=7.7,2.6Hz,1H),4.74(s,2H),4.27(t,J=5.4Hz ,2H),2.90(t,J=5.4Hz,2H),2.72-2.67(m,4H),2.57-2.53(m,4H),2.31(s,3H).

[0321] {6-[7-(2-morpholin-4-yl-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-(4-[1,2,3]triazol-1-yl-benzyl)-amine ("A68") [ka] From G2 and E4; white solid; mp 234-235°C; HPLC / MS [M+H] + 498. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.77(s,1H),8.52(s,1H),8.18(s ,1H),8.02-7.93(m,2H),7.86(d,J=8.2Hz,2H),7.57(d,J=8.0Hz,2H),7.10(d,J =2.6Hz,1H),6.92(s,1H),6.81(dd,J=7.7,2.6Hz,1H),4.67-4.61(m,2H),4.20( t,J=5.6Hz,2H),3.58(t,J=4.6Hz,4H),2.73(t,J=5.5Hz,2H),2.50-2.45(m,4H).

[0322] [6-(6-Fluoro-7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A69") [ka] (From G1; yellow solid; mp 299-300°C; HPLC / MS [M+H] + 430. 1 H NMR(400MHz,DMSO-d6)δ8.58(d,J=2.8Hz,1H),8.44(s,1H),8.27(s,1H),8.23-8.13(m,1H),8.08(s,1H),7.81(s ,1H),7.74-7.65(m,2H),7.51(d,J=7.8Hz,2H),7.37-7.26(m,2H),4.60-4.48(m,2H),3.95(s,3H),3.84(s,3H).

[0323] {6-[7-(2-pyrrolidin-1-yl-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-(4-[1,2,3]triazol-1-yl-benzyl)-amine ("A70") [ka] From G2 and E8; white solid; mp 250-251°C; HPLC / MS [M+H] + 482. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.78(s,1H),8.52(s,1H),8.18( s,1H),8.02-7.93(m,2H),7.90-7.83(m,2H),7.57(d,J=8.1Hz,2H),7.09(d,J=2 .6Hz,1H),6.92(s,1H),6.81(dd,J=7.7,2.6Hz,1H),4.64(d,J=5.3Hz,2H),4.1 8(t,J=5.7Hz,2H),2.83(t,J=5.7Hz,2H),2.57-2.51(m,4H),1.75-1.65(m,4H).

[0324] {6-[7-(2-Methoxy-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A71") [ka] From G3 and E1; white solid; mp 240-241°C; HPLC / MS [M+H] + 457. 1 H NMR(400MHz,DMSO-d6)δ9.71(d,J=7.8Hz,1H),8.52(s,1H),8.24-8.12(m,2H),7.94(t,J=6.2Hz,1H),7.80(d,J=8.1Hz,2H),7.49-7.40(m,2H),7. 10(d,J=2.6Hz,1H),6.91(s,1H),6.83(dd,J=7.8,2.7Hz,1H),4.66-4.55 (m,2H),4.26-4.20(m,2H),4.18(s,3H),3.74-3.68(m,2H),3.31(s,3H).

[0325] 6-[7-(benzyloxy)imidazo[1,2-a]pyridin-3-yl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A72") [ka] From G1; White solid; HPLC / MS (A) 1.43 min, [M+H] + 488. 1H NMR(500MHz,DMSO-d6)δ9.71(d,J=7.7Hz,1H),8.51(s,1H),8.15(s,1H),8.07(s,1H),7.84(t,J=6.1Hz,1H),7.81(s,1H),7.54-7.46(m,4H),7 .46-7.38(m,2H),7.40-7.31(m,3H),7.17(d,J=2.6Hz,1H),6.89(s,1H),6.87(dd,J=7.7,2.7Hz,1H),5.23(s,2H),4.54(bs,2H),3.84(s,3H).

[0326] [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-{6-[7-(2-pyrrolidin-1-yl-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A73") [ka] From G3 and E8; white solid; mp 235-236°C; HPLC / MS [M+H] + 496. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.21-8.16(m,1 H),7.94(t,1H),7.85-7.75(m,2H),7.45(d,J=7.8Hz,2H),7.10(d,J=2.6Hz, 1H),6.94-6.89(m,1H),6.82(dd,J=7.7,2.6Hz,1H),4.68-4.55(m,2H),4.3 5-4.06(m,5H),2.83(t,J=5.7Hz,2H),2.56-2.52(m,4H),1.81-1.59(m,4H).

[0327] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(3-morpholin-4-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A74") [ka] From G1 and E14; white solid; mp 213-214°C; HPLC / MS [M+H] + 496. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.17-8.12(m,1H),8.08(s,1H),7 .87(t,J=6.2Hz,1H),7.84(s,1H),7.55-7.48(m,2H),7.37-7.31(m,2H),7.07(d,J=2.6Hz,1H ),6.86(s,1H),6.80(dd,J=7.7,2.6Hz,1H),4.55-4.48(m,2H),4.13(t,J=6.3Hz,2H),3.84(s ,3H),3.58(t,J=4.6Hz,4H),2.44(t,J=7.2Hz,2H),2.40-2.35(m,4H),1.92(p,J=6.6Hz,2H).

[0328] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A75") [ka] From G1 and E15: Off-white solid; mp 213°C; UPLC / MS 0.377 min [M+H] + 509. 1H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.52(s,1H),8.14(s,1H),8.08(s,1H),7.83(t,J=6 .2Hz,1H),7.81(d,J=0.8Hz,1H),7.52(d,J=8.2Hz,2H),7.35(d,J=7.8Hz,2H),7.06(d,J=2.6Hz,1 H),6.89(d,J=1.3Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.54(d,J=5.9Hz,2H),4.14(t,J=6.3Hz,2H ),3.85(s,3H),2.55(t,J=7.2Hz,2H),2.49-2.41(m,4H),1.93(p,J=6.7Hz,2H),1.75-1.63(m,4H).

[0329] [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-{6-[7-(1-oxetan-3-yl-piperidin-4-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A76") [ka] (From G3 and E17) Yellow solid; MP 181-182°C; HPLC / MS [M+H] + 552. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.50(s,1H),8.20-8.07(m,2H),7.92(t,J= 6.1Hz,1H),7.82-7.73(m,2H),7.42(d,J=7.9Hz,2H),7.05(d,J=2.6Hz,1H),6.89(s,1H),6 .79(dd,J=7.7,2.6Hz,1H),4.70-4.47(m,4H),4.40(t,J=6.0Hz,2H),4.16(s,3H),3.94(d, J=5.8Hz,2H),3.40-3.33(m,1H),2.78-2.62(m,2H),1.87-1.62(m,5H),1.43-1.22(m,2H).

[0330] 6-{7-[2-(3,3-difluoropyrrolidin-1-yl)ethoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A77") [ka] From G1 and E18; pale orange solid; UPLC / MS 0.439 min, [M+H] + 531. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(s,1H),7.83(t,J=6.2H) z,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.3Hz,2H),7.34(d,J=7.8Hz,2H),7.10(d,J=2.6Hz,1H),6.89 (d,J=1.2Hz,1H),6.81(dd,J=7.7,2.6Hz,1H),4.54(d,J=5.3Hz,2H),4.20(t,J=5.5Hz,2H),3.84(s,3 H),3.00(t,J=13.5Hz,2H),2.88(t,J=5.5Hz,2H),2.82(t,J=7.0Hz,2H),2.24(tt,J=15.3,7.0Hz,2H).

[0331] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(1-oxetan-3-yl-piperidin-4-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A78") [ka] From G1 and E17; white solid; mp 241-242°C; HPLC / MS [M+H] + 551. 1H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.22-8.06(m,2H),7. 91-7.80(m,2H),7.55-7.48(m,2H),7.37-7.27(m,2H),7.09-7.04(m,1H),6.89(s, 1H),6.80(dd,J=7.7,2.6Hz,1H),4.59-4.37(m,6H),3.96(d,J=5.9Hz,2H),3.84(s ,3H),3.42-3.36(m,1H),2.75-2.68(m,2H),1.84-1.68(m,5H),1.41-1.27(m,2H).

[0332] {6-[7-(1-methyl-piperidin-4-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A79") [ka] From G3 and E19; white solid; mp 240-241°C; HPLC / MS [M+H] + 510. 1 H NMR(400MHz,DMSO-d6)9.70(d,J=7.8Hz,1H),8.51(s,1H),8.24-8.09(m,2H),7.93(t, J=6.2Hz,1H),7.79(d,J=8.2Hz,2H),7.51-7.39(m,2H),7.09-7.04(m,1H),6.90(s,1H) ,6.80(dd,J=7.8,2.6Hz,1H),4.66-4.51(m,2H),4.18(s,3H),3.94(d,J=5.8Hz,2H),2 .78(d,J=11.0Hz,2H),2.15(s,3H),1.85(t,2H),1.78-1.67(m,3H),1.39-1.25(m,2H).

[0333] {6-[7-(1-methyl-piperidin-4-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-(4-[1,2,3]triazol-1-yl-benzyl)-amine ("A80") [ka] From G2 and E19; white solid; mp 221-222°C; HPLC / MS [M+H] + 496. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.79(s,1H),8.52(s,1H),8.23-8.11(m,1H), 8.03-7.93(m,2H),7.91-7.83(m,2H),7.57(d,J=8.1Hz,2H),7.07(d,J=2.6Hz,1H),6.92(d, J=1.3Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.69-4.59(m,2H),3.95(d,J=5.9Hz,2H),2.80(d ,J=11.0Hz,2H),2.17(s,3H),1.98-1.70(m,2H),1.75(d,J=11.5Hz,3H),1.39-1.22(m,2H).

[0334] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-{7-nitroimidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A81") [ka] From G1; yellow powder; UPLC / MS 0.740 min, [M+H] + 427. 1H NMR(400MHz,DMSO-d6)δ9.99(d,J=7.8Hz,1H),8.73-8.53(m,3H),8.08(d,J=5.0Hz,2H),7.85(dd,J=7.7,2.5Hz,1H ),7.81(d,J=0.8Hz,1H),7.66-7.47(m,2H),7.35(d,J=7.8Hz,2H),7.10(d,J=1.2Hz,1H),4.58(s,2H),3.84(s,3H).

[0335] 6-{7-chloroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A82") [ka] From G1; Off-white solid; UPLC / MS 0.645 min, [M+H] + 416. 1 H NMR(400MHz,DMSO-d6)δ9.85(d,J=7.5Hz,1H),8.56(s,1H),8.32(s,1H),8.07(s,1H),7.95(t,J=6.1Hz,1H),7.88(dd,J=2.2,0.8Hz,1H),7.8 1(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.7Hz,2H),7.18(dd,J=7.5,2.3Hz,1H),6.98(d,J=1.2Hz,1H),4.55(s,2H),3.84(s,3H).

[0336] {6-[7-(1-oxetan-3-yl-piperidin-4-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-(4-[1,2,3]triazol-1-yl-benzyl)-amine ("A83") [ka] From G2 and E17; Off-white solid; mp 272-273°C; HPLC / MS [M+H] + 538. 1H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.81-8.76(m,1H),8.52(s,1H),8.18(s,1H),8.03-7 .93(m,2H),7.87(d,J=8.5Hz,2H),7.57(d,J=8.2Hz,2H),7.07(d,J=2.6Hz,1H),6.95-6.90(m,1H), 6.81(dd,J=7.7,2.6Hz,1H),4.64(s,2H),4.52(t,J=6.4Hz,2H),4.42(t,J=6.1Hz,2H),3.96(d,J=5 .8Hz,2H),2.75-2.68(m,2H),2.72(d,J=8.2Hz,2H),1.77(t,J=10.1Hz,5H),1.35(t,J=12.2Hz,2H).

[0337] [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A84") [ka] From G3 and E15; yellow solid; mp 251-242°C; HPLC / MS [M+H] + 510. 1 H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.8Hz,1H),8.51(s,1H),8.22-8.11(m,2H),7.93(t ,J=6.1Hz,1H),7.79(d,J=8.2Hz,2H),7.44(d,J=7.8Hz,2H),7.06(d,J=2.6Hz,1H),6.9 0(s,1H),6.80(dd,J=7.8,2.6Hz,1H),4.68-4.52(m,2H),4.17(s,3H),4.12(t,J=6.3H z,2H),2.60-2.53(m,2H),2.47-2.41(m,3H),1.92(p,J=6.7Hz,2H),1.77-1.60(m,4H).

[0338] 2-Methyl-1-(3-{6-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxy)-propan-2-ol ("A85") [ka] From G3 and E12; white solid; mp 195-196°C; HPLC / MS [M+H] + 471. 1 H NMR(400MHz,DMSO-d6)δ8.53(s,1H),8.22-8.10(m,2H),7.94(t,J=6.2Hz,1H),7.80(d,J=8.2Hz,2H),7.45(d,J=7.8Hz,2H),7.06(d ,J=2.6Hz,1H),6.91(d,J=1.2Hz,1H),6.83(dd,J=7.7,2.6Hz,1H),4.73(s,1H),4.60(s,2H),4.18(s,3H),3.84(s,2H),1.23(s,6H).

[0339] 7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzyloxy]-pyrimidin-4-yl}-imidazo[1,2-a]pyridine ("A86") [ka] From G4 and E9; Light brown solid; MP 210-211°C; HPLC / MS [M+H] + 525. 1H NMR(300MHz,DMSO-d6)δ9.75(d,J=7.7Hz,1H),8.83(d,J=1.1Hz,1H),8.48(s,1H),8 .13(s,1H),7.85(d,J=0.8Hz,1H),7.63-7.52(m,2H),7.47(d,J=1.2Hz,1H),7.45(d, J=8.1Hz,2H),7.15(d,J=2.6Hz,1H),6.87(dd,J=7.7,2.6Hz,1H),5.42(s,2H),4.18( t,J=5.6Hz,2H),3.84(s,4H),2.71(t,J=5.5Hz,2H),2.55-2.23(m,8H),2.14(s,3H).

[0340] 3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzyloxy]-pyrimidin-4-yl}-7-(2-pyrrolidin-1-yl-ethoxy)-imidazo[1,2-a]pyridine ("A87") [ka] From G4 and E8; white solid; mp 177-178°C; HPLC / MS [M+H] + 496. 1 H NMR(300MHz,DMSO-d6)δ9.75(d,J=7.7Hz,1H),8.83(d,J=1.0Hz,1H),8.48(s,1 H),8.13(s,1H),7.85(s,1H),7.57(d,J=8.2Hz,2H),7.49-7.42(m,3H),7.14(d ,J=2.6Hz,1H),6.87(dd,J=7.7,2.6Hz,1H),5.42(s,2H),4.17(t,J=5.6Hz,2H) ,3.84(s,3H),2.81(t,J=5.7Hz,2H),2.55-2.46(m,4H),1.67(p,J=3.0Hz,4H).

[0341] 4-[3-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)propyl]morpholin-3-one ("A88") [ka] From G1 and E20; off-white solid; UPLC / MS 0.478 min, [M+H] + 539. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.8Hz,1H),7.83(t,J= 6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.9Hz,2H),7.05(d,J=2.6Hz,1H),6.8 9(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.54(d,J=5.9Hz,2H),4.11(t,J=6.2Hz,2H),4.01(s,2H), 3.84(s,3H),3.84-3.81(m,3H),3.50(t,J=7.1Hz,2H),3.38(dd,J=5.9,4.4Hz,2H),2.02(p,J=6.5Hz,2H).

[0342] 6-{7-[2-(3-fluoropyrrolidin-1-yl)ethoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A89") [ka] From G1 and E21; off-white solid; UPLC / MS 0.382 min, [M+H] + 513. 1H NMR(500MHz,DMSO-d6)δ9.75(d,J=7.7Hz,1H),8.53(s,1H),8.24(s,1H),8.07(d ,J=0.9Hz,1H),7.92(t,J=6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H ),7.34(d,J=7.8Hz,2H),7.22(d,J=2.6Hz,1H),5.46(d,J=53.8Hz,1H),4.55(d, J=5.9Hz,2H),4.49(t,J=5.0Hz,2H),3.84(s,3H),3.9-3.1(m,6H),2.22(bs,2H).

[0343] 7-[2-(3,3-Difluoro-pyrrolidin-1-yl)-ethoxy]-3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzyloxy]-pyrimidin-4-yl}-imidazo[1,2-a]pyridine ("A90") [ka] From G4 and E18; white solid; mp 178-179°C; HPLC / MS [M+H] + 532. 1 H NMR(300MHz,DMSO-d6)δ9.76(d,J=7.7Hz,1H),8.84(d,J=1.1Hz,1H),8.49(s,1H),8.13(s,1H) ),7.86(s,1H),7.57(d,J=8.2Hz,2H),7.47(d,J=1.1Hz,1H),7.45(d,J=8.2Hz,2H),7.16(d,J= 2.7Hz,1H),6.89(dd,J=7.7,2.6Hz,1H),5.42(s,2H),4.20(t,J=5.5Hz,2H),3.84(s,3H),2.99 (t,J=13.5Hz,2H),2.87(t,J=5.4Hz,2H),2.80(t,J=7.0Hz,2H),2.23(tt,J=15.0,7.0Hz,2H).

[0344] {6-[7-(2,2-dimethyl-3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A91") [ka] From G1 and E22; white solid; mp 251-252°C; HPLC / MS [M+H] + 537. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.08(d,J=0.8Hz,1 H),7.87(t,J=6.1Hz,1H),7.81(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.9Hz,2H ),7.05(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.81(dd,J=7.7,2.6Hz,1H),4.54(s,2H),3. 84(s,3H),3.82(s,2H),2.57-2.51(m,4H),2.45(s,2H),1.63(p,J=3.0Hz,4H),0.98(s,6H).

[0345] 4-[2-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)ethyl]morpholin-3-one ("A92") [ka] From G1 and E24; Off-white solid; HPLC / MS (A) 1.19 min, [M+H] + 525. 1H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.8Hz,1H),7. 83(t,J=6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.13(d,J =2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.54(d,J=5.7Hz,2H),4.27(t,J= 5.6Hz,2H),4.05(s,2H),3.84(s,3H),3.84-3.81(m,2H),3.75(t,J=5.6Hz,2H),3.54-3.48(m,2H).

[0346] 1-methyl-4-[2-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)ethyl]piperazin-2-one ("A93") [ka] From G1 and E26; pale yellow resin; UPLC / MS 0.424 min, [M+H] + 538. 1 H NMR(500MHz,DMSO-d6)δ9.83(s,1H),8.60(s,1H),8.17(t,J=6.2Hz,1H),8.07(s,1H),7.81(d,J=0.8Hz,1H),7.58-7.47(m,2H),7.37-7.30(m,3H) ,7.24-7.14(m,1H),7.01(s,1H),4.57(s,2H),4.50(t,J=5.0Hz,2H),3.8 5(s,3H),3.64(s,2H),3.52-3.41(m,4H),3.42-3.19(m,4H),2.87(s,3H).

[0347] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-{7-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A94") [ka] From G1 and E27; yellow resin; UPLC / MS 0.376 min, [M+H] + 538.

[0348] 1-[2-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)ethyl]-4-(oxetan-3-yl)piperazin-2-one ("A95") [ka] From G1 and E28: Off-white needles; HPLC / MS (A) 1.16 min, [M+H] + 580. 1 H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.8Hz,1H),7.83(t,J=6.1Hz, 1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.13(d,J=2.7Hz,1H),6.89(d,J=1.2Hz,1 H),6.80(dd,J=7.7,2.6Hz,1H),4.54(t,J=6.6Hz,2H),4.44(t,J=6.1Hz,2H),4.25(t,J=5.6Hz,2H),3.84(s,3H),3 .72(t,J=5.6Hz,2H),3.52(p,J=6.2Hz,1H),3.47(dd,J=6.1,4.8Hz,2H),2.97(s,2H),2.58(dd,J=6.2,4.7Hz,2H).

[0349] N-{[4-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methyl}-6-{7-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A96") [ka] From G3 and E27; pale yellow solid; UPLC / MS 0.367 min, [M+H] + 539.

[0350] 5-Fluoro-6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A97") [ka] From G5; Off-white powder; UPLC / MS 0.519 min, [M+H] + 430. 1 H NMR(500MHz,DMSO-d6)δ9.77(d,J=7.8Hz,1H),8.37(d,J=2.2Hz,1H),8.28(t,J=6.2Hz,1H),8.14(d,J=3.9Hz,1H),8.07(s,1H),7.81(d,J=0. 6Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=8.2Hz,2H),7.15(d,J=2.6Hz,1H),6.85(dd,J=7.7,2.7Hz,1H),4.65(d,J=6.1Hz,2H),3.91(s,3H).

[0351] (6-{7-[2-(1-methyl-1H-imidazol-2-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A98") [ka] From G3 and E30; White solid; mp 240-241°C; HPLC / MS [M+H] + 507. 1 H NMR(300MHz,DMSO-d6)δ9.23(s,1H),8.78(d,J=19.4Hz,2H),8.18(s,1H),8.12(s,2H),7.79(d,J=7.9Hz,2H),7.63(dd,J=17.3, 1.9Hz,2H),7.48(d,J=2.5Hz,3H),7.40-7.26(m,2H),4.75(s,2H),4.66(t,J=5.6Hz,2H),4.14(s,3H),3.86(s,3H),3.58(s,2H).

[0352] 6-{7-[2-(azetidin-1-yl)ethoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A99") [ka] From G1 and E31; white powder; UPLC / MS 0.362 min, [M+H] + 481. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.52(s,1H),8.14(s,1H),8.08(s,1H),7.83(t, J=6.2Hz,1H),7.81(d,J=0.8Hz,1H),7.52(d,J=8.3Hz,2H),7.35(d,J=7.8Hz,2H),7.05(d,J=2 .6Hz,1H),6.89(d,J=1.3Hz,1H),6.78(dd,J=7.7,2.6Hz,1H),4.55(d,J=6.0Hz,2H),4.03(t,J =5.5Hz,2H),3.85(s,3H),3.20(t,J=6.9Hz,4H),2.74(t,J=5.5Hz,2H),1.98(p,J=6.9Hz,2H).

[0353] 6-{7-[2-(azetidin-1-yl)ethoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A100") [ka] From G3 and E31; off-white powder; UPLC / MS 0.364 min, [M+H] + 482. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.52(s,1H),8.17(s,1H),8.15(s,1H) ,7.89(t,J=6.2Hz,1H),7.80(d,J=8.3Hz,2H),7.45(d,J=7.8Hz,2H),7.05(d,J=2.6Hz ,1H),6.91(d,J=1.2Hz,1H),6.78(dd,J=7.7,2.6Hz,1H),4.60(d,J=6.0Hz,2H),4.03 (t,J=5.5Hz,2H),3.20(t,J=6.9Hz,4H),2.75(t,J=5.5Hz,2H),1.98(p,J=6.9Hz,2H).

[0354] 6-{7-[3-(3,3-difluoropyrrolidin-1-yl)propoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A101") trifluoroacetate [ka] From G1 and E32; off-white powder; UPLC / MS 0.408 min, [M+H] + 545. 1H NMR(500MHz,DMSO-d6)δ9.83(s,1H),8.60(s,1H),8.16(t,J=6.1Hz,1H),8.07( d,J=0.8Hz,1H),7.81(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.9Hz ,2H),7.28(d,J=2.6Hz,1H),7.14(d,J=7.7Hz,1H),7.00(s,1H),4.57(s,2H),4 .28(t,J=6.0Hz,2H),3.85(s,3H),2.15(p,J=5.9Hz,3H),4.0-3.0(broad signal).

[0355] Example 3 Synthesis of 6-{7-[3-(azetidin-1-yl)propoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine}pyrimidin-4-amine ("A102") [ka] To a suspension of 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine (H1) in dioxane (48 ml), 3-(azetidin-1-yl)propan-1-ol (415 mg, 3.60 mmol) is added and the mixture is flushed with argon. Potassium tert-butanolate (1.01 g, 9.01 mmol) is added in portions. The mixture is heated to 100 °C and stirred at this temperature for 18 hours. When the reaction mixture reaches room temperature, it is treated with methanol and evaporated. The residue is taken up in water. The solid is filtered off, washed with water and dried. The residue is chromatographed on a silica gel column using dichloromethane / methanol as eluent to give 6-{7-[3-(azetidin-1-yl)propoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine}pyrimidin-4-amine as an off-white solid; HPLC / MS (B) 0.639 min, [M+H]+ 495. 1 H NMR(500MHz,DMSO-d6)δ8.51(s,1H),8.13(s,1H),8.07(d,J=0.8Hz,1H),7.82(t,J=6.1Hz,1H),7.8 0(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.03(d,J=2.5Hz,1H),6.89(d,J=1. 2Hz,1H),6.78(dd,J=7.7,2.6Hz,1H),4.54(d,J=6.0Hz,2H),4.09(t,J=6.4Hz,2H),3.84(s,3H),3.1 7(s,1H),3.09(t,J=6.9Hz,4H),2.46(t,J=6.9Hz,2H),1.94(p,J=6.9Hz,2H),1.73(p,J=6.6Hz,2H).

[0356] The following compounds are prepared analogously: [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-(6-{7-[2-(6-oxa-3-aza-bicyclo[3.1.1]hept-3-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A103") [ka] From H1; White solid; MP 185-187°C; HPLC / MS [M+H] + 523. 1H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.6Hz,1H),8.52(s,1H),8.22-8.14(m,1H),8.10(s,1H),7.89(t,J =6.1Hz,1H),7.82(s,1H),7.52(d,J=8.1Hz,2H),7.39-7.28(m,2H),7.14(d,J=2.6Hz,1H),6.90(s,1H) ),6.83(dd,J=7.7,2.6Hz,1H),4.58-4.49(m,2H),4.44(d,J=6.2Hz,2H),4.26(t,J=5.7Hz,2H),3.85( s,3H),3.17-3.09(m,2H),3.05-2.96(m,2H),2.88-2.82(m,1H),2.81-2.74(m,2H),2.22-2.16(m,1H).

[0357] {6-[7-(2-amino-2-methyl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A104") [ka] From H1; White solid; MP 224-225°C; HPLC / MS [M+H] + 469. 1 H NMR(300MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.15(s,1H),8.0 9(s,1H),7.88(t,J=6.1Hz,1H),7.82(s,1H),7.51(d,J=8.2Hz,2H),7.34(d, J=7.9Hz,2H),7.03(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.83(dd,J=7.7, 2.6Hz,1H),4.54(s,2H),3.84(s,3H),3.77(s,2H),1.23(s,2H),1.12(s,6H).

[0358] (6-{7-[2-(3,3-difluoro-pyrrolidin-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A105") [ka] From H2; White solid; MP 257-258°C; HPLC / MS [M+H] + 532. 1 H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.8Hz,1H),8.50(s,1H),8.17(s,1H),7.93(t, J=6.1Hz,1H),7.78(d,J=8.2Hz,2H),7.42(d,J=7.9Hz,2H),7.10(s,1H),6.89(s,1 H),6.81(dd,J=7.7,2.3Hz,1H),4.58(s,2H),4.28-3.98(m,5H),2.99(t,J=13.5H z,2H),2.86(t,J=5.3Hz,2H),2.79(t,J=7.0Hz,2H),2.23(tt,J=15.2,6.9Hz,2H).

[0359] [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-{6-[7-(pyridin-2-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A106") [ka] From H2; White solid; MP 240-241°C; HPLC / MS [M+H] + 490. 1H NMR(300MHz,DMSO-d6)δ9.72(d,J=7.7Hz,1H),8.59(dt,J=4.7,1.5Hz,1H),8.50(s,1H ),8.16(s,1H),7.92(t,J=6.1Hz,1H),7.85(td,J=7.7,1.8Hz,1H),7.78(d,J=8.2Hz,2H ),7.57(d,J=7.8Hz,1H),7.42(d,J=8.0Hz,2H),7.36(ddd,J=7.6,4.8,1.2Hz,1H),7.1 6(d,J=2.6Hz,1H),6.93-6.88(m,2H),5.28(s,2H),4.58(d,J=5.8Hz,2H),4.16(s,3H).

[0360] {6-[7-(2-methyl-2-morpholin-4-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A107") [ka] From H1; White solid; MP 233-234°C; HPLC / MS [M+H] + 539. 1 H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.52(s,1H),8.15(s,1H),8.08(s,1H),7.8 7(t,J=6.1Hz,1H),7.81(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.9Hz,2H),7. 13(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.82(dd,J=7.7,2.6Hz,1H),4.53(d,J=5.9Hz, 2H),3.96(s,2H),3.84(s,3H),3.55(t,J=4.5Hz,4H),2.61(t,J=4.5Hz,4H),1.12(s,6H).

[0361] [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-(6-{7-[2-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A108") [ka] From H2; White solid; MP 245-246°C; HPLC / MS [M+H] + 524. 1 H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.50(s,1H),8.16(s,1H),8.14( s,1H),7.91(t,J=6.1Hz,1H),7.77(d,J=8.2Hz,2H),7.42(d,J=7.9Hz,2H),7.03 (d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.76(dd,J=7.7,2.6Hz,1H),4.62-4.54 (m,6H),4.16(s,3H),4.00(t,J=5.4Hz,2H),3.30(s,4H),2.70(t,J=5.3Hz,2H).

[0362] {6-[7-(2-methyl-2-morpholin-4-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A109") [ka] From H2; White solid; mp 220-221°C; HPLC / MS [M+H] + 540. 1H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.50(s,1H),8.15(d,J=6.9Hz,2H),7.91(t,J=6.2Hz,1H),7.77(d,J=8.2Hz,2H),7.42(d,J=7.9Hz) ,2H),7.12(d,J=2.6Hz,1H),6.92-6.78(m,2H),4.58(s,2H),4.16(s,3H) ,3.95(s,2H),3.54(t,J=4.5Hz,4H),2.60(d,J=4.9Hz,4H),1.11(s,6H).

[0363] {6-[7-(1-methyl-1H-imidazol-2-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A110") [ka] From H3; White solid; MP 255-256°C; HPLC / MS [M+H] + 493. 1 H NMR(300MHz,DMSO-d6)δ9.70(d,J=7.4Hz,1H),8.48(d,J=15.2Hz,2H),7.78(d,J=7.8Hz,2H),7.43 (s,2H),7.34(s,1H),7.20(s,1H),6.86(d,J=21.4Hz,3H),5.25(s,2H),4.06(s,3H),3.68(s,3H).

[0364] (6-{7-[2-(1-methyl-1H-imidazol-2-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A111") [ka] From H1; White solid; MP 215-216°C; HPLC / MS [M+H] + 506. 1 H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.8Hz,1H),8.51(s,1H),8.21-8.12(m,1H),8.0 8(s,1H),7.87(t,J=6.1Hz,1H),7.81(s,1H),7.51(d,J=8.1Hz,2H),7.34(d,J=7.9 Hz,2H),7.07(dd,J=12.6,1.9Hz,2H),6.89(d,J=1.3Hz,1H),6.83-6.74(m,2H),4. 53(s,2H),4.42(t,J=6.5Hz,2H),3.84(s,3H),3.63(s,3H),3.15(t,J=6.5Hz,2H).

[0365] [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-{6-[7-(pyridin-3-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A112") [ka] From H2; White solid; MP 280-281°C; HPLC / MS [M+H] + 490. 1 H NMR(300MHz,DMSO-d6)δ9.71(d,J=7.7Hz,1H),8.71(d,J=2.2Hz,1H),8.60-8.47(m,2H),8.16(s,2H),7.98-7.85(m,2H),7 .78(d,J=8.2Hz,2H),7.52-7.36(m,3H),7.22(d,J=2.6Hz,1H),6.93-6.82(m,2H),5.27(s,2H),4.58(s,2H),4.16(s,3H).

[0366] {6-[7-(1-methyl-1H-imidazol-2-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A113") [ka] From H1; White solid; MP 271-272°C; HPLC / MS [M+H] + 492. 1 H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.49(s,1H),8.23-8.12(m,1H),8.07(s,1H),7.87(t,J=6.1Hz,1H),7.80(s,1H), 7.54-7.46(m,2H),7.42-7.28(m,3H),7.20(s,1H),6.92-6.75(m,3H),5.25(s,2H),4.55-4.49(m,2H),3.83(s,3H),3.68(s,3H).

[0367] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-(6-{7-[2-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A114") [ka] From H1; yellow solid; mp 234-235°C; HPLC / MS [M+H] + 523. 1 H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.49(s,1H),8.19-8.10(m,1H),8.0 7(s,1H),7.86(t,J=6.1Hz,1H),7.80(s,1H),7.54-7.45(m,2H),7.36-7.25(m,2H) ,7.03(d,J=2.6Hz,1H),6.87(d,J=1.2Hz,1H),6.76(dd,J=7.7,2.6Hz,1H),4.58(s ,4H),4.55-4.45(m,2H),4.00(t,J=5.3Hz,2H),3.34(s,4H),2.70(t,J=5.3Hz,2H).

[0368] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-(6-{7-[2-(1-methyl-pyrrolidin-3-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A115") [ka] From H1; White solid; MP 219-220°C; HPLC / MS [M+H] + 509. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.25-8.05(m,2H),7.88(t,J=6.2Hz,1H),7.82(s,1H) ),7.57-7.49(m,2H),7.35(d,J=7.8Hz,2H),7.07(d,J=2.6Hz,1H),6.89(s,1H),6.80(dd,J=7.7,2.6Hz,1H),4.6 2-4.45(m,2H),4.08(t,J=6.6Hz,2H),3.85(s,3H),3.49-3.31(m,1H),2.68(t,J=8.9,7.3Hz,1H),2.45-2.34(m, 1H),2.34-2.21(m,4H),2.18-2.09(m,1H),2.04-1.91(m,1H),1.91-1.75(m,2H),1.44(ddt,J=12.3,8.3,6.1Hz).

[0369] (6-{7-[2-(1-methyl-pyrrolidin-3-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A116") [ka] From H2; White solid; mp 220-221°C; HPLC / MS [M+H] + 510. 1H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.50(s,1H),8.15(d,J=7.5Hz,2H),7.90(t,J=6.2Hz,1H),7 .81-7.74(m,2H),7.42(d,J=7.9Hz,2H),7.05(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.77(dd,J=7.7,2.6 Hz,1H),4.58(d,J=6.0Hz,2H),4.16(s,3H),4.06(t,J=6.6Hz,2H),2.64(dd,J=8.7,7.3Hz,1H),2.45-2.29 (m,2H),2.20(s,4H),2.09(dd,J=8.8,6.6Hz,1H),2.01-1.89(m,1H),1.85-1.73(m,2H),1.46-1.34(m,1H).

[0370] {6-[7-((R)-4-methyl-morpholin-2-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A117") [ka] From H1; White solid; mp 221-222°C; HPLC / MS [M+H] + 511. 1 H NMR(300MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.25-8.12(m,1H),8.08(s,1H),7.87(t,J =6.1Hz,1H),7.81(s,1H),7.56-7.47(m,2H),7.38-7.29(m,2H),7.09(d,J=2.6Hz,1H),6.89(s,1H),6. 82(dd,J=7.7,2.6Hz,1H),4.64-4.49(m,2H),4.09(d,J=5.0Hz,2H),3.84(s,4H),3.83-3.78(m,1H),3. 60-3.48(m,1H),2.82(d,J=10.5Hz,1H),2.64(d,J=11.1Hz,1H),2.29-2.20(m,3H),2.09-1.89(m,2H).

[0371] {6-[7-((S)-4-methyl-morpholin-2-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A118") [ka] From H1; White solid; MP 224-225°C; HPLC / MS [M+H] + 511. 1 H NMR(300MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.22-8.12(m,1H),8.08(s,1H),7.87(t,J=6 .2Hz,1H),7.81(s,1H),7.56-7.47(m,2H),7.38-7.29(m,2H),7.09(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H ),6.82(dd,J=7.7,2.6Hz,1H),4.60-4.46(m,2H),4.09(d,J=5.0Hz,2H),3.84(s,4H),3.82-3.78(m,1H), 3.62-3.49(m,1H),2.81(d,J=11.2Hz,1H),2.63(d,J=11.3Hz,1H),2.29-2.17(m,3H),2.06-1.87(m,2H).

[0372] [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-(6-{7-[2-(1-oxetan-3-yl-pyrrolidin-3-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A119") [ka] From H2; White solid; MP 224-225°C; HPLC / MS [M+H] + 552. 1H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.50(s,1H),8.15(d,J=7.5Hz,2H),7.91(t,J=6.1Hz,1H),7.82-7.71(m,2) H),7.42(d,J=7.8Hz,2H),7.06(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.77(dd,J=7.7,2.6Hz,1H),4.53(td,J=6.5,1.8H z,4H),4.42(td,J=6.0,1.5Hz,2H),4.16(s,3H),4.07(t,J=6.5Hz,2H),3.53(t,J=6.2Hz,1H),2.70(t,J=7.9Hz,1H),2.3 9(q,J=8.2Hz,1H),2.25(q,J=7.8Hz,1H),2.15-2.04(m,1H),2.03-1.08(m,1H),1.81(q,J=6.7Hz,2H),1.51-1.36(m,1H).

[0373] {6-[7-(3-Azetidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A120") [ka] From H2; white solid; UPLC / MS 0.372min, [M+H] + 496. 1H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.52(s,1H),8.17(s,1H),8.15(s,1H),7.89(t, J=6.2Hz,1H),7.80(d,J=8.3Hz,2H),7.45(d,J=7.8Hz,2H),7.05(d,J=2.6Hz,1H),6.91(d,J=1 .3Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.61(d,J=5.9Hz,2H),4.18(s,3H),4.10(t,J=6.4Hz,2 H),3.10(t,J=6.9Hz,4H),2.47(t,J=7.0Hz,2H),1.95(p,J=6.9Hz,2H),1.74(p,J=6.7Hz,2H).

[0374] {6-[7-((R)-4-メチル-モルホリン-2-イルメトキシ)-イミダゾ[1,2-a]ピリジン-3-イル]-ピリミジン-4-イル}-[4-(2-メチル-2H-[1,2,3]トリアゾール-4-イル)-ベンジル]-アミン(「A121」)

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[0375] {6-[7-((S)-4-methyl-morpholin-2-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A122") [ka] From H2; White solid; MP 200-201°C; HPLC / MS [M+H] + 512. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.50(s,1H),8.16(s,2H),7.91(t,J=6.1Hz,1H),7.82-7.7 3(m,2H),7.42(d,J=7.9Hz,2H),7.07(d,J=2.7Hz,1H),6.89(d,J=1.3Hz,1H),6.81(dd,J=7.7,2.6Hz,1H), 4.58(d,J=6.0Hz,2H),4.16(s,3H),4.07(d,J=5.0Hz,2H),3.85-3.75(m,2H),3.59-3.47(m,1H),2.77(d, J=11.0Hz,1H),2.59(d,J=11.5Hz,1H),2.19(s,3H),1.99(td,J=11.4,3.4Hz,1H),1.88(t,J=10.6Hz,1H).

[0376] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-(6-{7-[2-(1-oxetan-3-yl-pyrrolidin-3-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A123") [ka] From H1; White solid; MP 231-232°C; HPLC / MS [M+H] + 551. 1H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.23-8.13(m,1H),8.09(s,1H),7.88(t,J=6.2Hz,1H),7.82(s,1H),7.56-7. 49(m,2H),7.35(d,J=7.8Hz,2H),7.08(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.56(td,J=6.4,2.4Hz,4H),4 .45(td,J=5.9,1.9Hz,2H),4.10(t,J=6.6Hz,2H),3.85(s,3H),3.61-3.50(m,1H),2.77-2.68(m,1H),2.57-2.52(m,1H),2.41(td,J=8.6, 5.5Hz,1H),2.34-2.21(m,1H),2.12(dd,J=8.8,7.0Hz,1H),2.05-1.92(m,1H),1.84(q,J=6.9Hz,2H),1.45(ddt,J=12.6,8.3,6.3Hz,1H).

[0377] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-(7-{[(3R)-4-methylmorpholin-3-yl]methoxy}imidazo[1,2-a]pyridin-3-yl)pyrimidin-4-amine ("A124") [ka] From H1; Off-white powder; HPLC / MS (A) 1.034 min, [M+H] + 511. 1H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.8Hz,1H),7.83(t,J=6.1Hz,1H),7.80(d,J=0. 8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.13(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4. 54(d,J=5.8Hz,2H),4.22(dd,J=10.4,4.2Hz,1H),4.02(dd,J=10.4,6.0Hz,1H),3.89-3.85(m,1H),3.70(dt,J=11.0,3.1Hz,1H),3. 56-3.48(m,1H),3.38(dd,J=11.2,9.3Hz,1H),2.69(dt,J=11.8,2.7Hz,1H),2.50-2.43(m,1H),2.25(ddd,J=11.8,10.3,3.3Hz,1H).

[0378] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-(7-{[(3S)-4-methylmorpholin-3-yl]methoxy}imidazo[1,2-a]pyridin-3-yl)pyrimidin-4-amine ("A125") [ka] (from H1); Off-white powder; HPLC / MS (A) 1.034 min, [M+H] + 511. 1H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.8Hz,1H),7.83(t,J=6.1Hz,1H),7.80(d,J=0. 8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.13(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4. 54(d,J=5.8Hz,2H),4.22(dd,J=10.4,4.2Hz,1H),4.02(dd,J=10.4,6.0Hz,1H),3.89-3.85(m,1H),3.70(dt,J=11.0,3.1Hz,1H),3. 56-3.48(m,1H),3.38(dd,J=11.2,9.3Hz,1H),2.69(dt,J=11.8,2.7Hz,1H),2.50-2.43(m,1H),2.25(ddd,J=11.8,10.3,3.3Hz,1H).

[0379] [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-{6-[7-(2-pyridin-3-yl-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A126") [ka] From H2; HPLC / MS [M+H] + 504.

[0380] (6-{7-[2-(3-Aza-bicyclo[3.1.0]hex-3-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A127") [ka] From H1; White solid; MP 219-220°C; HPLC / MS [M+H] + 507. 1H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.22-8.12(m,1H),8.08(s,1H),7.87(t,J =6.1Hz,1H),7.81(s,1H),7.56-7.47(m,2H),7.38-7.29(m,2H),7.11-7.05(m,1H),6.89(d,J=1.3Hz,1 H),6.79(dd,J=7.7,2.6Hz,1H),4.58-4.49(m,2H),4.21-4.07(m,2H),3.84(s,3H),3.01(d,J=8.6Hz,2 H),2.91-2.76(m,2H),2.42-2.33(m,2H),1.42-1.31(m,2H),0.58(d,J=3.9Hz,1H),0.37-0.24(m,1H).

[0381] (6-{7-[2-(3-Aza-bicyclo[3.1.0]hex-3-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A128") [ka] From H2; White solid; mp 220-221°C; HPLC / MS [M+H] + 508. 1 H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.50(s,1H),8.16(s,2H),7.94-7.75(m,3H),7.43(d,J=8.0Hz,2H),7.06(s,1H),6.90-6.75(m ,2H),4.58(s,2H),4.13(d,J=16.6Hz,5H),3.00(d,J=8.5Hz,2H),2.80(s,2H),2.36(d,J=8.5Hz,2H),1.34(s,2H),0.57(s,1H),0.28(s,1H).

[0382] (6-{7-[2-(1-methyl-piperidin-4-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A129") [ka] From H1; White solid; MP 261-262°C; HPLC / MS [M+H] + 523.

[0383] (6-{7-[2-(1-methyl-piperidin-4-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A130") [ka] From H2; White solid; MP 230-231°C; HPLC / MS [M+H] + 524. 1 H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.50(s,1H),8.15(d,J=8.0Hz,2H),7.91(t,J=6.1 Hz,1H),7.78(d,J=8.0Hz,2H),7.42(d,J=7.9Hz,2H),7.07(d,J=2.6Hz,1H),6.89(s,1H),6.77(dd ,J=7.7,2.6Hz,1H),4.58(d,J=6.0Hz,2H),4.16(s,3H),4.10(t,J=6.6Hz,2H),2.71(d,J=11.1Hz ,2H),2.11(s,3H),1.80(t,J=11.3Hz,2H),1.72-1.61(m,4H),1.40(s,1H),1.22(t,J=12.3Hz,2H)

[0384] 3-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxy)-propan-1-ol ("A131") [ka] From H1; yellow solid; mp 216-217°C; HPLC / MS [M+H] + 456. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.08(s,1H),7. 86(t,J=6.2Hz,1H),7.81(s,1H),7.51(d,J=7.8Hz,2H),7.34(d,J=7.8Hz,2H),7.06(d,J =2.7Hz,1H),6.89(s,1H),6.79(dd,J=7.7,2.6Hz,1H),4.58(t,J=5.2Hz,1H),4.56-4.45 (m,2H),4.15(t,J=6.3Hz,2H),3.84(s,3H),3.58(q,J=5.9Hz,2H),1.91(p,J=6.3Hz,2H).

[0385] {6-[7-(3-dimethylamino-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A132") [ka] From H1; White solid; MP 232-233°C; HPLC / MS [M+H] + 483. 1H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.19-8.10(m,1H),8.08(s,1H) ),7.86(t,J=6.1Hz,1H),7.81(s,1H),7.51(d,J=8.1Hz,2H),7.34(d,J=7.8Hz,2H),7.05(d ,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.60-4.48(m,2H),4.1 1(t,J=6.3Hz,2H),3.84(s,3H),2.37(t,J=7.1Hz,2H),2.15(s,6H),1.89(p,J=6.7Hz,2H).

[0386] (6-{7-[2-(1-methyl-pyrrolidin-3-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A133") [ka] From H2; White solid; HPLC / MS [M+H] + 526.

[0387] 3-(3-{6-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxy)-propan-1-ol ("A134") [ka] From H2; White solid; MP 240-241°C; HPLC / MS [M+H] + 457. 1H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.8Hz,1H),8.53-8.47(m,1H),8.16(s,2H ),7.90(t,J=6.3Hz,1H),7.82-7.73(m,2H),7.42(d,J=7.9Hz,2H),7.04(d,J= 2.7Hz,1H),6.89(d,J=1.3Hz,1H),6.78(dd,J=7.7,2.6Hz,1H),4.57(t,J=5. 1Hz,3H),4.15(d,J=7.7Hz,5H),3.56(q,J=5.9Hz,2H),1.89(p,J=6.1Hz,2H).

[0388] {6-[7-(3-dimethylamino-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A135") [ka] From H2; pale yellow solid; mp 250-251°C; HPLC / MS [M+H] + 484. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.50(s,1H),8.15(d,J=7.2Hz,2H),7 .90(t,J=6.2Hz,1H),7.82-7.73(m,2H),7.42(d,J=7.9Hz,2H),7.03(d,J=2.6Hz,1H) ,6.89(d,J=1.3Hz,1H),6.78(dd,J=7.7,2.6Hz,1H),4.58(d,J=6.1Hz,2H),4.16(s,3 H),4.09(t,J=6.4Hz,2H),2.35(t,J=7.2Hz,2H),2.14(s,6H),1.87(p,J=6.6Hz,2H).

[0389] 6-{7-[2-(3,3-difluoropiperidin-1-yl)ethoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A136") [ka] From H1; Off-white solid; HPLC / MS (B) 0.695 min, [M+H] + 545. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.8Hz,1H),7.82(t,J=6 .2Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.13-7.08(m,1H),6.89(d,J= 1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.54(d,J=6.0Hz,2H),4.21(t,J=5.6Hz,2H),3.84(s,3H),2.86(t,J =5.6Hz,2H),2.79(t,J=11.7Hz,2H),2.55(t,J=5.4Hz,2H),1.87(tt,J=13.9,6.4Hz,2H),1.71-1.57(m,2H).

[0390] 6-{7-[3-(diethylamino)propoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A137") [ka] From H1; off-white solid; UPLC / MS 0.395min, [M+H] + 511. 1H NMR(500MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.52-8.46(m,1H),8.13(s,1H),8.07(d,J=0.8Hz,1H),7. 82(t,J=6.2Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.04(d,J=2.7H z,1H),6.89(d,J=1.3Hz,1H),6.78(dd,J=7.7,2.6Hz,1H),4.54(d,J=6.0Hz,2H),4.12(t,J=6.3Hz,2H), 3.84(s,3H),2.53(t,J=7.0Hz,2H),2.46(q,J=7.1Hz,4H),1.85(p,J=6.6Hz,2H),0.95(t,J=7.1Hz,6H).

[0391] 4-[2-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)ethyl]-1lambda 6-thiomorpholine-1,1-dione ("A138") [ka] From H1; Off-white solid; UPLC / MS 0.467 min, [M+H] + 559. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.8Hz ,1H),7.83(t,J=6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz ,2H),7.11(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.54(d,J =6.0Hz,2H),4.21(t,J=5.5Hz,2H),3.84(s,3H),3.16-3.02(m,8H),2.97(t,J=5.5Hz,2H).

[0392] 6-{7-[2-(3,3-difluoroazetidin-1-yl)ethoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A139") [ka] From H1; off-white solid; UPLC / MS 0.443min, [M+H] + 517. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.8Hz, 1H),7.83(t,J=6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2 H),7.07(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.54(d,J=6. 0Hz,2H),4.12(t,J=5.3Hz,2H),3.84(s,3H),3.69(t,J=12.4Hz,4H),2.96(t,J=5.3Hz,2H).

[0393] 6-{7-[2-(3-fluoroazetidin-1-yl)ethoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A140") [ka] From H1; off-white solid; UPLC / MS 0.372min, [M+H] + 499. 1H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.13(s,1H),8.07(d,J=0.8Hz,1H),7.83(t,J=6.2Hz,1H ),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.05(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H), 6.78(dd,J=7.7,2.6Hz,1H),5.15(dddd,J=57.9,10.2,5.6,4.6Hz,1H),4.69-4.45(m,2H),4.07(t,J=5.3Hz,2H),3. 84(s,3H),3.64(dddd,J=15.3,7.6,5.6,2.0Hz,2H),3.21(dddd,J=23.9,7.5,4.6,2.1Hz,2H),2.86(t,J=5.3Hz,2H).

[0394] 4-methyl-1-[2-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)ethyl]piperazin-2-one ("A141") [ka] From H1; off-white solid; UPLC / MS 0.380min, [M+H] + 538. 1H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.7Hz,1H),7.83(t, J=6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.12(d,J=2.6Hz,1H) ,6.89(d,J=1.3Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.54(d,J=6.0Hz,2H),4.24(t,J=5.7Hz,2H),3.84( s,3H),3.70(t,J=5.6Hz,2H),3.44(dd,J=6.1,4.9Hz,2H),2.94(s,2H),2.68-2.54(m,2H),2.20(s,3H).

[0395] 6-{7-[3-(3,3-ジフルオロアゼチジン-1-イル)プロポキシ]イミダゾ[1,2-a]ピリジン-3-イル} -N-{[4-(1-メチル-1H-ピラゾール-4-イル)フェニル]メチル}ピリミジン-4-アミン(「A142」)

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[0396] {6-[7-(3-methanesulfonyl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A143") [ka] From H1; White solid; mp 300°C; HPLC / MS [M+H] + 518. 1 H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.50(s,1H),8.10(d,J=23.3Hz,2H ),7.91-7.75(m,2H),7.54-7.45(m,2H),7.32(d,J=7.8Hz,2H),7.08(d,J=2.6Hz,1 H),6.88(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.52(d,J=5.8Hz,2H),4.20 (t,J=6.2Hz,2H),3.83(s,3H),3.30-3.19(m,2H),3.02(s,3H),2.26-2.10(m,2H).

[0397] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-{7-[(1-methylazetidin-3-yl)methoxy]imidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A144") [ka] From H1; off-white solid; UPLC / MS 0.365min, [M+2H] / 2 241. 1H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.14(s,1H),8.08(s,1H),7.83(t,J= 6.2Hz,1H),7.81(s,1H),7.52(d,J=8.2Hz,2H),7.35(d,J=7.8Hz,2H),7.08(d,J=2.6Hz,1H),6.90 (d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.54(d,J=5.8Hz,2H),4.21(d,J=6.9Hz,2H),3.85 (s,3H),3.32-3.27(m,2H),2.98(dd,J=7.0,5.6Hz,2H),2.79(tt,J=7.4,5.8Hz,1H),2.22(s,3H).

[0398] 1-[3-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)propyl]pyrrolidin-2-one ("A145") [ka] From H1; off-white solid; HPLC / MS (B) 0.734min, [M+H] + 518. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(s,1H),7.83(t, J=6.2Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.04(d,J=2. 6Hz,1H),6.89(d,J=1.2Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.54(d,J=5.5Hz,2H),4.08(t,J= 6.2Hz,2H),3.84(s,3H),3.36(dt,J=9.2,7.0Hz,4H),2.21(t,J=8.1Hz,2H),2.04-1.77(m,4H).

[0399] {6-[7-(3-amino-3-methyl-butoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A223") [ka] From H1; White solid; MP 252-253°C; HPLC / MS [M+H] + 483. 1 H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.49(s,1H),8.13(s,1H),8.06( s,1H),7.82(d,J=16.2Hz,2H),7.54-7.45(m,2H),7.32(d,J=7.8Hz,2H),7.09(d ,J=2.6Hz,1H),6.87(d,J=1.2Hz,1H),6.75(dd,J=7.7,2.6Hz,1H),4.52(d,J=5. 9Hz,2H),4.18(t,J=7.2Hz,2H),3.83(s,3H),1.80(t,J=7.2Hz,2H),1.09(s,6H)

[0400] {6-[7-(2-methanesulfonyl-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A224") [ka] From H1; White solid; HPLC / MS [M+H] + 504. 1H NMR(300MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.50(s,1H),8.16(s,1H),8.07(s, 1H),7.87(t,J=6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.54-7.45(m,2H),7.32(d,J=7 .9Hz,2H),7.19(d,J=2.6Hz,1H),6.88(d,J=1.2Hz,1H),6.82(dd,J=7.7,2.6Hz,1 H),4.49(dt,J=11.4,5.6Hz,4H),3.82(s,3H),3.67(t,J=5.6Hz,2H),3.08(s,3H).

[0401] {6-[7-(3-methanesulfonyl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A231") [ka] from H2; white solid; mp 300°C; HPLC / MS [M+H] + 519. 1 H NMR(300MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.50(s,1H),8.16(s,2H),7. 91(t,J=6.2Hz,1H),7.77(d,J=8.1Hz,2H),7.42(d,J=7.8Hz,2H),7.08(d,J= 2.6Hz,1H),6.90(s,1H),6.80(dd,J=7.7,2.6Hz,1H),4.58(s,2H),4.21(d, J=6.1Hz,2H),4.16(s,3H),3.26(s,2H),3.02(s,3H),2.18(t,J=7.9Hz,2H).

[0402] (6-{7-[2-(3-amino-oxetan-3-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A233") [ka] From H1; White solid; mp 240-241°C; HPLC / MS [M+H] + 497. 1 H NMR(300MHz,DMSO-d6)δ9.73-9.63(m,1H),8.49(s,1H),8.10(d,J=19.3Hz,2H),7.92-7.82(m,1H),7 .80(s,1H),7.50(d,J=8.0Hz,2H),7.32(d,J=7.9Hz,2H),7.10-7.02(m,1H),6.91-6.74(m,2H),4.52( s,2H),4.42(d,J=5.7Hz,1H),4.31(d,J=5.8Hz,1H),4.21(t,J=6.6Hz,1H),3.98(s,1H),3.82(s,4H) ,3.55(dd,J=79.3,8.5Hz,1H),2.17(t,J=6.7Hz,2H),2.00-1.88(m,1H),1.72(dt,J=11.7,5.7Hz,1H)

[0403] 2-[2-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxy)-ethoxy]-ethanol ("A234") [ka] From H1; White solid; mp 240-241°C; HPLC / MS [M+H] + 486. 1H NMR(300MHz,DMSO-d6) 9.68(d,J=7.7Hz,1H),8.49(s,1H),8.14(s,1H),8.07(s,1H),7.86(t,J=6.2Hz,1H),7. 80(s,1H),7.50(d,J=8.1Hz,2H),7.32(d,J=7.9Hz,2H),7.08(d,J=2.6Hz,1H),6.87(d, J=1.3Hz,1H),6.81(dd,J=7.7,2.6Hz,1H),4.66-4.60(m,1H),4.52(s,2H),4.19(dd,J= 5.9,3.2Hz,2H),3.82(s,3H),3.77(dd,J=5.5,3.4Hz,2H),3.50(dt,J=8.1,3.9Hz,4H).

[0404] 2-(3-{6-[4-(2-methyl-oxazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxy)-ethanol ("A236") [ka] From H4; White solid; MP 266-267°C; HPLC / MS [M+H] + 443. 1 H NMR(400MHz,DMSO-d6)δ9.71(d,J=7.6Hz,1H),8.51(s,1H),8.42(s,1H),8.17- 8.13(m,1H),7.93-7.87(m,1H),7.71(d,J=8.1Hz,2H),7.40(d,J=7.7Hz,2H),7. 08(d,J=2.6Hz,1H),6.90(s,1H),6.81(dd,J=7.7,2.7Hz,1H),4.95(t,J=5.6Hz ,1H),4.63-4.52(m,2H),4.10(t,J=4.7Hz,2H),3.80-3.72(m,2H),2.45(s,3H).

[0405] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-{7-[3-(piperidin-1-yl)propoxy]imidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A237") [ka] From H1; white solid; UPLC / MS 0.396 min, [M+H] + 523. 1 H NMR(500MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.51(s,1H),8.13(s,1H),8.07(d,J=0.7Hz,1H),7.82(t,J= 6.2Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.05(d,J=2.6Hz,1H),6.8 8(d,J=1.3Hz,1H),6.78(dd,J=7.7,2.6Hz,1H),4.54(d,J=5.9Hz,2H),4.11(t,J=6.4Hz,2H),3.84(s,3H), 2.39(t,J=7.2Hz,2H),2.37-2.31(m,4H),1.90(p,J=6.7Hz,2H),1.50(p,J=5.5Hz,4H),1.42-1.33(m,2H).

[0406] 2-{3-[6-(4-oxazol-4-yl-benzylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyridin-7-yloxy}-ethanol ("A251") [ka] From H6; Off-white solid; mp244~245℃; HPLC / MS[M+H] + 429. 1H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.58(s,1H),8.50(s,1H),8.4 3(s,1H),8.14(s,1H),7.91(t,J=6.1Hz,1H),7.74(d,J=8.0Hz,2H),7.41(d,J =8.0Hz,2H),7.06(d,J=2.6Hz,1H),6.88(s,1H),6.80(dd,J=7.8,2.6Hz,1H), 4.94(t,J=5.4Hz,1H),4.57(s,2H),4.09(t,J=4.7Hz,2H),3.80-3.71(m,2H).

[0407] (4-Oxazol-4-yl-benzyl)-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A252") [ka] White solid; HPLC / MS[M+H] + 496.

[0408] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-(7-{[1-(2,2,2-trifluoroethyl)azetidin-3-yl]methoxy}imidazo[1,2-a]pyridin-3-yl)pyrimidin-4-amine ("A254") [ka] From H1) white crystalline solid; HPLC / MS (B) 0.717min, [M+H] + 549. 1H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.8Hz,1H),7 .83(t,J=6.2Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.09(d ,J=2.6Hz,2H),6.89(d,J=1.3Hz,1H),6.81(dd,J=7.7,2.6Hz,1H),4.54(d,J=6.1Hz,2H),4.23(d ,J=6.8Hz,2H),3.84(s,3H),3.53(t,J=7.4Hz,2H),3.26-3.17(m,4H),2.93(hept,J=6.9Hz,1H).

[0409] N-{[4-(1-メチル-1H-ピラゾール-4-イル)フェニル]メチル}-6-{7-[2-(1H-ピラゾール-1-イル)エトキシ]イミダゾ[1,2-a]ピリジン-3-イル}ピリミジン-4-アミン(「A255」)

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[0410] 6-{7-[(3-fluoro-1-methylazetidin-3-yl)methoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A256") [ka] (from H1); off-white powder; UPLC / MS 0.379 min, [M+H] + 499. 1 H NMR(500MHz,DMSO-d6)δ9.71(d,J=7.7Hz,1H),8.52(s,1H),8.15(s,1H),8.07(d,J=0.8Hz,1H), 7.84(t,J=6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.17 (d,J=2.6Hz,1H),6.90(d,J=1.2Hz,1H),6.85(dd,J=7.7,2.7Hz,1H),4.54(d,J=6.0Hz,2H),4.4 2(d,J=24.4Hz,2H),3.84(s,3H),3.58-3.51(m,2H),3.17(dd,J=21.7,9.5Hz,2H),2.34(s,3H).

[0411] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-{7-[3-(1H-pyrazol-1-yl)propoxy]imidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A257") [ka] From H1; off-white powder; UPLC / MS 0.511min, [M+H] + 506. 1H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.13(s,1H),8.07(d,J=0.8Hz,1H),7.83(t,J=6.1H z,1H),7.80(d,J=0.8Hz,1H),7.74(dd,J=2.2,0.7Hz,1H),7.51(d,J=8.2Hz,2H),7.44(dd,J=1.8,0.7Hz,1H),7 .34(d,J=7.8Hz,2H),7.02(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),6.23(t,J=2.0H z,1H),4.54(d,J=6.1Hz,2H),4.30(t,J=6.9Hz,2H),4.06(t,J=6.1Hz,2H),3.84(s,3H),2.26(p,J=6.5Hz,2H).

[0412] N-{[4-(1-メチル-1H-ピラゾール-4-イル)フェニル]メチル}-6-(7-{3-[(オキセタン-3 -イル)アミノ]プロポキシ}イミダゾ[1,2-a]ピリジン-3-イル)ピリミジン-4-アミン(「A258」)

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[0413] N-{[4-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methyl}-6-(7-{3-[(oxetan-3-yl)amino]propoxy}imidazo[1,2-a]pyridin-3-yl)pyrimidin-4-amine ("A259") [ka] From H2; White solid; HPLC / MS [M+H] + 512. 1 H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.18(s,1H),8.16(s,1H),7.92(t, J=6.2Hz,1H),7.82-7.78(m,2H),7.44(d,J=7.5Hz,2H),7.07(d,J=2.8Hz,1H),6.91(s,1H),6. 80(dd,J=7.7,2.6Hz,1H),4.63(t,J=6.6Hz,2H),4.60(s,2H),4.33(t,J=6.2Hz,2H),4.18(s,3 H),4.14(t,J=6.4Hz,2H),3.86(p,J=6.7Hz,1H),2.60(t,J=6.7Hz,2H),1.85(p,J=6.6Hz,2H).

[0414] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-[7-(3-{[(3R)-oxolan-3-yl]amino}propoxy)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine ("A260") [ka] From H1; White solid; HPLC / MS [M+H] + 524. 1 H NMR(500MHz,DMSO-d6)δ9.72(d,J=7.7Hz,1H),8.52(s,1H),8.16(s,1H),8.09(d,J=0.8Hz,1H),7.89(t,J=6.2Hz,1H), 7.82(d,J=0.8Hz,1H),7.55-7.49(m,2H),7.35(d,J=7.8Hz,2H),7.11(d,J=2.6Hz,1H),6.91(d,J=1.2Hz,1H),6.82(dd ,J=7.7,2.6Hz,1H),4.54(s,2H),4.21(t,J=6.2Hz,2H),3.96-3.81(m,5H),3.78(dd,J=9.6,5.8Hz,1H),3.67(td,J=8. 2,6.3Hz,1H),3.07(q,J=8.6,6.9Hz,2H),2.21(dtd,J=13.9,8.0,6.0Hz,1H),2.14(q,J=6.9Hz,2H),2.05-1.96(m,1H). The compound may also be referred to as [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-[6-(7-{3-[(R)-(tetrahydro-furan-3-yl)amino]-propoxy}-imidazo[1,2186-pyridin-3-yl)-pyrimidin-4-yl]-amine.

[0415] 4-methyl-1-[2-({3-[6-({[4-(2-methyl-1,3-oxazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)ethyl]-1,4-diazepan-5-one ("A261") [ka] From H4; White solid; HPLC / MS [M+H] + 553. 1H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.40(s,1H),8.14(s,1H),7.8 6(t,J=6.2Hz,1H),7.70(d,J=7.9Hz,2H),7.40(d,J=7.8Hz,2H),7.09(d,J=2.6Hz,1H),6. 89(s,1H),6.79(dd,J=7.6,2.6Hz,1H),4.57(d,J=6.1Hz,2H),4.20(t,J=5.6Hz,2H),3.45 -3.40(m,2H),2.86(d,J=13.7Hz,5H),2.71-2.61(m,4H),2.56-2.50(m,2H),2.44(s,3H).

[0416] 6-{7-[3-(4-fluoro-4-methylpiperidin-1-yl)propoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A262") [ka] From H1; White solid; HPLC / MS [M+H] + 555. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.08(d,J=0.8Hz,1H ),7.86(t,J=6.1Hz,1H),7.81(d,J=0.8Hz,1H),7.54-7.48(m,2H),7.34(d,J=7.7Hz,2H),7.07 (s,1H),6.89(d,J=1.2Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.54(s,2H),4.13(s,2H),3.84(s, 3H),2.60(s,1H),2.49(s,2H),2.23(s,2H),1.93(s,2H),1.73(s,4H),1.32(d,J=21.5Hz,3H). The compound may also be referred to as (6-{7-[3-(4-fluoro-4-methyl-piperidin-1-yl)-propoxy]-imidazo[1,2187-pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine.

[0417] 6-{7-[3-(4-fluoro-4-methylpiperidin-1-yl)propoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1,3-oxazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A263") [ka] From H6; White solid; HPLC / MS [M+H] + 543. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.58(d,J=1.0Hz,1H),8.51(s,1H),8.43(d,J=1.0Hz,1H),8.15(s,1H) ),7.89(t,J=6.2Hz,1H),7.79-7.72(m,2H),7.43(d,J=7.9Hz,2H),7.06(d,J=2.6Hz,1H),6.90(d,J=1.2Hz,1H),6.79 (dd,J=7.7,2.7Hz,1H),4.58(s,2H),4.12(t,J=6.3Hz,2H),3.28(s,3H),2.63-2.57(m,1H),2.46(t,J=7.1Hz,2H),2. 22(t,J=10.6Hz,2H),1.92(p,J=6.6Hz,2H),1.71(dd,J=13.5,9.3Hz,2H),1.69-1.57(m,1H),1.30(d,J=21.5Hz,3H).

[0418] N-{[4-(2-methyl-1,3-oxazol-4-yl)phenyl]methyl}-6-[7-(2-{4H,5H,6H,7H-[1,2,3]triazolo[1,5-a]pyrazin-5-yl}ethoxy)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine ("A264") [ka] From H4; White solid; HPLC / MS [M+H] + 543. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.41(s,1H),8.15(s,1H),7.88(t ,J=6.1Hz,1H),7.74-7.67(m,2H),7.53(s,1H),7.40(d,J=7.9Hz,2H),7.14(d,J=2.6Hz,1H), 6.90(d,J=1.3Hz,1H),6.82(dd,J=7.7,2.6Hz,1H),4.59-4.54(m,1H),4.37(t,J=5.6Hz,2H), 4.30(t,J=5.5Hz,2H),3.88(s,2H),3.09(t,J=5.6Hz,2H),3.03(t,J=5.4Hz,2H),2.45(s,3H).

[0419] 6-[7-(2-{4H,5H,6H,7H-[1,2,3]triazolo[1,5-a]pyrazin-5-yl}ethoxy)imidazo[1,2-a]pyridin-3-yl]-N-{[4-(trifluoromethoxy)phenyl]methyl}pyrimidin-4-amine ("A265") [ka] From H7; White solid; HPLC / MS [M+H] + 552. 1H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52-8.51(m,1H),8.19-8.14(m,1H),7.9 1(t,J=6.2Hz,1H),7.54-7.53(m,1H),7.50-7.46(m,2H),7.35-7.31(m,2H),7.15-7.13(m ,1H),6.90(d,J=1.2Hz,1H),6.82(dd,J=7.7,2.6Hz,1H),4.62-4.57(m,2H),4.39-4.35(m ,2H),4.30(t,J=5.5Hz,2H),3.89-3.88(m,2H),3.11-3.08(m,2H),3.03(t,J=5.5Hz,2H).

[0420] Example 4 Synthesis of 6-{imidazo[1,2-a]pyridin-3-yl}-N-({6-[(3R)-3-methoxypyrrolidin-1-yl]pyridin-3-yl}methyl)pyrimidin-4-amine ("A146") [ka] Off-white solid;mp161~163℃;HPLC / MS[M+H] + 402. 1 H NMR(400MHz,DMSO-d6)δ9.85(d,J=7.1Hz,1H),8.56(s,1H),8.29(s,1H),8.11(s,1H),7.82( t,J=6.0Hz,1H),7.71(dt,J=8.9,1.2Hz,1H),7.56-7.48(m,1H),7.41(ddd,J=9.2,6.7,1.3Hz ,1H),7.10(td,J=6.9,1.3Hz,1H),6.94(s,1H),6.43(d,J=8.6Hz,1H),4.40(s,2H),4.08-4.0 1(m,1H),3.44(d,J=3.7Hz,3H),3.33-3.29(m,1H),3.24(s,3H),2.03(td,J=8.1,4.4Hz,2H).

[0421] The following compounds are prepared analogously: (6-Imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-(6-pyrrolidin-1-yl-pyridin-3-ylmethyl)-amine ("A147") [ka] Yellow solid; mp176~177℃; HPLC / MS[M+H] + 372. 1 H NMR(400MHz,DMSO-d6)δ9.85(d,J=7.2Hz,1H),8.56(s,1H),8.31(s,1H),8.10 (s,1H),7.80(t,J=6.0Hz,1H),7.71(dt,J=9.1,1.2Hz,1H),7.51(dd,J=8.7,2. 4Hz,1H),7.41(m,J=9.0,6.7,1.3Hz,1H),7.10(td,J=6.9,1.3Hz,1H),6.94(s, 1H),6.42(d,J=8.7Hz,1H),4.40(s,2H),3.35-3.32(m,4H),1.94-1.90(m,4H).

[0422] N-({6-[(3S)-3-fluoropyrrolidin-1-yl]pyridin-3-yl}methyl)-6-{imidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A148") [ka] Off-white solid;mp190~192℃;HPLC / MS[M+H] + 390. 1H NMR(400MHz,DMSO-d6)δ9.85(d,J=7.1Hz,1H),8.57(s,1H),8.30(s,1H),8.13(s,1H),7. 84(t,J=6.0Hz,1H),7.71(dt,J=9.0,1.2Hz,1H),7.59-7.52(m,1H),7.42(ddd,J=9.0,6.8 ,1.3Hz,1H),7.10(td,J=6.9,1.3Hz,1H),6.95(s,1H),6.49(dd,J=8.6,0.8Hz,1H),5.43 (d,J=53.6Hz,1H),4.42(s,2H),3.74-3.48(m,3H),3.44-3.37(m,1H),2.28-2.07(m,2H).

[0423] [6-(3-Aza-bicyclo[3.1.0]hex-3-yl)-pyridin-3-ylmethyl]-(6-imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-amine ("A149") [ka] White solid;mp185~187℃;HPLC / MS[M+H] + 384. 1 H NMR(400MHz,DMSO-d6)δ9.85(d,J=6.9Hz,1H),8.56(s,1H),8.09(s,1H),7.82(t,J=6.0Hz,1H), 7.71(dt,J=9.0,1.2Hz,1H),7.50(d,J=8.6Hz,1H),7.41(ddd,J=9.1,6.8,1.4Hz,1H),7.10(td, J=6.9,1.3Hz,1H),6.93(s,1H),6.42(d,J=8.6Hz,1H),4.39(s,2H),3.60(d,J=10.1Hz,2H),3.2 9(dt,J=10.1,1.9Hz,2H),1.69-1.61(m,2H),0.70(td,J=7.8,4.4Hz,1H),0.15(q,J=4.1Hz,1H).

[0424] [6-(3,3-Difluoro-pyrrolidin-1-yl)-pyridin-3-ylmethyl]-(6-imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-amine ("A150") [ka] White solid;mp192~194℃;HPLC / MS[M+H] + 408. 1 H NMR(400MHz,DMSO-d6)δ9.85(d,J=7.0Hz,1H),8.56(s,1H),8.30(s,1H),8.16(s,1H),7.86 (t,J=6.0Hz,1H),7.71(dt,J=9.0,1.2Hz,1H),7.60(d,J=8.5Hz,1H),7.42(ddd,J=9.0,6.8, 1.3Hz,1H),7.10(td,J=6.9,1.3Hz,1H),6.95(s,1H),6.54(dd,J=8.6,0.8Hz,1H),4.44(s,2 H),3.80(t,J=13.4Hz,2H),3.58(t,J=7.3Hz,2H),2.58-2.52(m,1H),2.47(d,J=7.3Hz,1H).

[0425] 6-{imidazo[1,2-a]pyridin-3-yl}-N-({6-[(3S)-3-methoxypyrrolidin-1-yl]pyridin-3-yl}methyl)pyrimidin-4-amine ("A151") [ka] White solid;mp159~161℃;HPLC / MS[M+H] + 402. 1H NMR(400MHz,DMSO-d6)δ9.85(d,J=7.0Hz,1H),8.56(s,1H),8.28(s,1H),8.11(s,1H),7.83(t,J= 6.0Hz,1H),7.71(dt,J=9.0,1.2Hz,1H),7.56-7.48(m,1H),7.41(ddd,J=9.0,6.8,1.3Hz,1H),7. 09(td,J=6.9,1.3Hz,1H),6.94(s,1H),6.47-6.38(m,1H),4.40(s,2H),4.04(p,J=3.6Hz,1H),3. 47-3.38(m,3H),3.36(s,3H),3.31(td,J=9.9,9.4,7.6Hz,1H),2.02(td,J=8.6,8.2,4.5Hz,2H).

[0426] (4-Fluoro-6-pyrrolidin-1-yl-pyridin-3-ylmethyl)-(6-imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-amine ("A152") [ka] Off-white solid;mp239~241℃;HPLC / MS[M+H] + 390. 1 H NMR(400MHz,DMSO-d6)δ9.85(d,J=7.1Hz,1H),8.58(s,1H),8.28(s,1H),8. 13(d,J=11.3Hz,1H),7.77(s,1H),7.71(dt,J=9.0,1.2Hz,1H),7.42(ddd,J= 9.0,6.8,1.3Hz,1H),7.10(td,J=6.9,1.3Hz,1H),6.96(s,1H),6.27(d,J=1 3.1Hz,1H),4.45(d,J=5.6Hz,2H),3.35(d,J=2.7Hz,4H),1.98-1.88(m,4H).

[0427] N-({6-[(3R)-3-fluoropyrrolidin-1-yl]pyridin-3-yl}methyl)-6-{imidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A153") [ka] White solid;mp188~190℃;HPLC / MS[M+H] + 390. 1 H NMR(400MHz,DMSO-d6)δ9.85(d,J=7.0Hz,1H),8.56(s,1H),8.29(s,1H),8.13(s,1H),7. 84(t,J=6.0Hz,1H),7.71(dt,J=9.0,1.2Hz,1H),7.62-7.51(m,1H),7.41(ddd,J=9.0,6.7 ,1.3Hz,1H),7.10(td,J=6.9,1.3Hz,1H),6.94(s,1H),6.48(d,J=8.5Hz,1H),5.52-5.31 (m,1H),4.42(s,2H),3.75-3.46(m,3H),3.39(dd,J=10.4,6.9Hz,1H),2.28-2.05(m,2H).

[0428] Example 5 Synthesis of (6-imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-(4-methyl-6-pyrrolidin-1-yl-pyridin-3-ylmethyl)-amine ("A154") [ka] Off-white solid; mp195~197℃. 1 H NMR(400MHz,DMSO-d6)δ9.85(d,J=7.0Hz,1H),8.58(s,1H),7.98(s,1H),7.71(dd,J=9.0,1.2Hz,1H),7.63(t,J=5.4Hz,1H),7.46-7 .37(m,1H),7.10(td,J=6.9,1.3Hz,1H),6.94(s,1H),6.29(s,1H),4.41(s,2H),3.38-3.35(m,4H),2.27(s,3H),1.97-1.87(m,4H).

[0429] The following compounds are prepared analogously: [6-((S)-3-Fluoro-pyrrolidin-1-yl)-4-methyl-pyridin-3-ylmethyl]-(6-imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-amine ("A155") [ka] White solid; mp187~190℃; HPLC / MS[M+H] + 404. 1 H NMR(400MHz,DMSO-d6)δ9.85(d,J=6.9Hz,1H),8.58(s,1H),8.28(d,J=8.4Hz,1H),8.01(s,1H),7.75-7.67(m,1H),7.65(t,J=5.5Hz,1H),7.4 6-7.37(m,1H),7.15-7.06(m,1H),6.95(s,1H),6.37(s,1H),5.42(d,J =53.8Hz,1H),4.49-4.38(m,2H),3.75-3.47(m,4H),2.29(s,3H),2.24- 2.04(m,2H).

[0430] [6-((R)-3-Fluoro-pyrrolidin-1-yl)-4-methyl-pyridin-3-ylmethyl]-(6-imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-amine ("A156") White solid; mp184~197℃; HPLC / MS[M+H] + 404. 1 H NMR(400MHz,DMSO-d6)δ9.85(d,J=7.0Hz,1H),8.58(s,1H),8.35-8.13(m,1H),8.01(s,1H),7.71(dd,J=9.0,1.2Hz,1H),7.65(t,J=5.5Hz,1H),7. 45-7.38(m,1H),7.15-7.06(m,1H),6.95(s,1H),6.37(s,1H),5.52-5.32 (m,1H),4.44(s,2H),3.75-3.40(m,4H),2.29(s,3H),2.25-2.06(m,2H).

[0431] Example 6 Synthesis of (6-imidazo[1,2-a]pyridin-3-yl-pyrimidin-4-yl)-[4-(1H-imidazol-2-yl)-benzyl]-amine ("A157") [ka] White solid;mp300℃;HPLC / MS[M+H] + 368. 1 H NMR(400MHz,DMSO-d6)δ12.44(s,1H),9.85(d,J=7.0Hz,1H),8.57(s,1H),8.30(s,1H),7.97(t,J=6.1Hz,1H),7 .92-7.86(m,2H),7.71(m,1H),7.46-7.37(m,3H),7.21(s,1H),7.09(m,1H),6.99(d,J=1.6Hz,2H),4.61(s,2H).

[0432] Example 7 Synthesis of 7-methoxy-3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzyloxy]-pyrimidin-4-yl}-imidazo[1,2-a]pyridine ("A158") [ka] White solid; mp216~218℃; HPLC / MS[M+H] + 413. 1 H NMR(400MHz,DMSO-d6)δ9.77(d,J=8Hz,1H),8.85(d,J=1.1Hz,1H),8.50(s,1H),8.15(s,1H),7.87(d,J=0.8Hz,1H),7. 63-7.55(m,2H),7.51-7.43(m,3H),7.15(d,J=2.4Hz,1H),6.88(dd,J=7.7,2.7Hz,1H),5.44(s,2H),3.89-3.83(m,6H).

[0433] Example 8 Synthesis of N-[(4-{1-[(azetidin-3-yl)methyl]-1H-pyrazol-4-yl}phenyl)methyl]-6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A159") trifluoroacetate [ka] Yellow resin; HPLC / MS (B) 1.017min, [M+H] + 467.

[0434] Example 9 Synthesis of 3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-ol ("A160") [ka] From "A72"; Light brown powder; UPLC / MS 0.450 min, [M+H] + 398. 1 H NMR(400MHz,DMSO-d6)δ10.52(s,1H),9.68(d,J=7.6Hz,1H),8.50(s,1H),8.25-8.02(m,3H),7.84(t,J=6.3Hz,1H),7.82(s,1H),7.52(d, J=8.3Hz,2H),7.34(d,J=7.9Hz,2H),6.86(d,J=1.3Hz,1H),6.81(d,J=2.4Hz,1H),6.72(dd,J=7.6,2.6Hz,1H),4.53(s,2H),3.84(s,3H).

[0435] Example 10 Synthesis of [4-(4-{[6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-ylamino]-methyl}-phenyl)-2-methyl-2H-pyrazol-3-yl]-methanol ("A161") [ka] Grayish-white solid; mp 263~264℃; HPLC / MS [M+H] + 442. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.17(s,1H),7.92(t,J=6.1Hz,1H),7.56(s,1H),7.49-7.33(m,5H),7.09(d,J=2.6H z,1H),6.91(d,J=1.2Hz,1H),6.82(dd,J=7.9,2.6Hz,1H),5.36(t,J=5.2Hz,1H),4.57(s,2H),4.52(d,J=5.2Hz,2H),3.88(s,3H),3.87(s,3H).

[0436] Example 11 6-{7-アミノイミダゾ[1,2-a]ピリジン-3-イル}-N-{[4-(1-メチル-1 Synthesis of H-ピラゾール-4-イル)フェニル]メチル}ピリミジン-4-アミン(「A162」)

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[0437] Example 12 Synthesis of 2-methyl-2-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-ylamino)-propan-1-ol ("A163") [ka] White solid;mp228~229℃;HPLC / MS[M+H] + 469. 1 H NMR(300MHz,DMSO-d6)δ9.42(d,J=7.7Hz,1H),8.45(s,1H),8.09(s,1H),7.96(s,1H) ,7.81(s,1H),7.74(t,J=6.0Hz,1H),7.51(d,J=8.1Hz,2H),7.33(d,J=7.9Hz,2H),6. 78(s,1H),6.63(dd,J=7.8,2.2Hz,1H),6.51(d,J=2.3Hz,1H),5.94(s,1H),4.91(t,J =5.7Hz,1H),4.51(d,J=5.7Hz,2H),3.84(s,2H),3.45(d,J=5.7Hz,2H),1.29(s,6H).

[0438] Example 13 Synthesis of N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-[7-(piperidin-4-yloxy)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine ("A164") [ka] A suspension of 6-[(E)-2-ethoxyethenyl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine (G1) (168 mg, 0.50 mmol) in a mixture of 1,4-dioxane (1.5 mL) and water (0.5 mL) was cooled to 0 °C, N-bromosuccinimide (98 mg, 0.55 mmol) was added, and the reaction mixture was stirred at 0 °C for 20 minutes. tert-Butyl 4-[(2-aminopyridin-4-yl)oxy]piperidine-1-carboxylate (E23) (147 mg, 0.50 mmol) was added. The reaction solution was heated to 60 °C and stirred at this temperature for 5 hours. After the reaction mixture reached room temperature, it was poured into 1N aqueous NaOH solution (13 mL). The resulting precipitate is filtered off, washed with water, dried and chromatographed on a silica gel column using dichloromethane / methanol as eluent to give tert-butyl 4-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)piperidine-1-carboxylate as a pale beige solid; HPLC / MS (A) 1.50 min, [M+H] + 581. 1 H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.8Hz,1H),7.83(t,J=6.2 Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.19(d,J=2.6Hz,1H),6.88(d,J=1 .2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.75(tt,J=8.0,3.7Hz,1H),4.54(d,J=6.0Hz,2H),3.84(s,3H),3.69( dt,J=13.1,4.8Hz,2H),3.25-3.18(m,2H),2.04-1.92(m,2H),1.57(dtd,J=12.9,8.8,3.7Hz,2H),1.41(s,9H).

[0439] A suspension of tert-butyl 4-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)piperidine-1-carboxylate in a 4N solution of hydrochloric acid in dioxane is stirred at room temperature for 1.5 hours. The reaction mixture is evaporated under reduced pressure, and the residue is triturated with tert-butyl methyl ether to give N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-[7-(piperidin-4-yloxy)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine hydrochloride as a beige solid; HPLC / MS (A) 1.06 min, [M+H] + 481. 1 H NMR(500MHz,DMSO-d6)δ9.83(s,1H),9.02(s,2H),8.70(s,1H),8.61(s,1H),8.28(s,1H),8. 08(d,J=0.8Hz,1H),7.81(d,J=0.9Hz,1H),7.52(d,J=8.2Hz,2H),7.45(d,J=2.6Hz,1H),7.34 (d,J=7.8Hz,2H),7.27(dd,J=7.7,2.5Hz,1H),7.05(s,1H),5.03(p,J=3.8Hz,1H),4.58(s,2 H),3.85(s,3H),3.40-3.22(m,2H),3.21-3.09(m,2H),2.32-2.08(m,2H),2.04-1.85(m,2H).

[0440] The following compounds are prepared analogously: [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(piperidin-4-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A165") [ka] Yellow solid; mp224~225℃; HPLC / MS[M+H] + 496. 1H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.19(s,1H),8.16(s,1H),7.94 (t,J=6.2Hz,1H),7.80(d,J=8.2Hz,2H),7.44(d,J=7.8Hz,2H),7.07(d,J=2.6Hz,1H),6.91 (d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.60(s,2H),4.18(s,3H),3.93(d,J=6.4Hz, 2H),2.99(d,J=11.9Hz,2H),2.01-1.82(m,1H),1.72(d,J=11.9Hz,2H),1.32-1.11(m,2H).

[0441] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(piperidin-4-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A166") [ka] (from G1 and E16); white solid; mp 211-212°C; HPLC / MS [M+H] + 495. 1 H NMR(400MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.15(s,1H),8.10(s,1H),7.89(t ,J=6.2Hz,1H),7.82(s,1H),7.52(d,J=8.1Hz,2H),7.34(d,J=7.8Hz,2H),7.07(d,J=2.6Hz,1H ),6.89(d,J=1.2Hz,1H),6.80(dd,J=7.7,2.6Hz,1H),4.54(s,2H),3.93(d,J=6.3Hz,2H),3.85 (s,3H),3.00(d,J=11.9Hz,2H),1.95-1.83(m,1H),1.73(d,J=12.7Hz,2H),1.33-1.17(m,2H).

[0442] 6-{7-[(azetidin-3-yl)methoxy]imidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A167") [ka] (from G1 and E29); off-white powder; UPLC / MS 0.358 min, [M+H] + 467. 1 H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(s,1H),7.86(t,J =6.1Hz,1H),7.80(s,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.09(d,J=2.6Hz,1H),6. 90(s,1H),6.80(dd,J=7.7,2.6Hz,1H),4.54(d,J=6.1Hz,2H),4.32-4.12(m,2H),3.84(s,3H),3. 69(t,J=7.7Hz,1H),3.64-3.51(m,1H),3.46-3.30(m,2H),3.09-2.92(m,1H),2.75-2.66(m,1H).

[0443] Example 14 Synthesis of [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(2-pyrrolidin-1-yl-ethyl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A168") [ka] White solid;mp214~215℃;HPLC / MS[M+H] + 479. 1H NMR(400MHz,CD3OD)δ9.77(d,J=7.2Hz,1H),8.56(d,J=1.2Hz,1H),8.15(s, 1H),7.95(s,1H),7.81(d,J=0.8Hz,1H),7.59-7.49(m,3H),7.43-7.36(m,2H ),7.03(dd,J=7.2,1.7Hz,1H),6.91(s,1H),4.66-4.57(m,2H),3.93(s,3H), 3.03-2.96(m,2H),2.92-2.85(m,2H),2.76-2.66(m,4H),1.94-1.80(m,4H).

[0444] The following compounds are prepared analogously: (6-{7-[2-(3,3-difluoro-pyrrolidin-1-yl)-ethyl]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A169") [ka] Yellow solid; mp205~206℃; HPLC / MS[M+H] + 515. 1 H NMR(400MHz,DMSO-d6)δ9.73(d,J=7.2Hz,1H),8.55(s,1H),8.24(s,1H),8.09(s,1H),7.91 (t,J=6.2Hz,1H),7.82(d,J=0.8Hz,1H),7.57(s,1H),7.53(d,J=8.2Hz,2H),7.35(d,J=7.9 Hz,2H),7.03(dd,J=7.2,1.8Hz,1H),6.94(d,J=1.2Hz,1H),4.56(s,2H),3.85(s,3H),2.96 (t,J=13.5Hz,2H),2.85(t,J=7.0Hz,2H),2.81-2.71(m,4H),2.23(tt,J=14.9,6.9Hz,2H).

[0445] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-(6-{7-[2-(4-oxetan-3-yl-piperazin-1-yl)-ethyl]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A170") [ka] White solid; mp220~221℃; HPLC / MS[M+H] + 550. 1 H NMR(400MHz,DMSO-d6)δ9.72(d,J=7.2Hz,1H),8.55(s,1H),8.24(s,1H),8.09(s,1 H),7.91(t,J=6.2Hz,1H),7.82(s,1H),7.63-7.46(m,3H),7.35(d,J=7.9Hz,2H),7 .02(dd,J=7.3,1.7Hz,1H),6.94(d,J=1.2Hz,1H),4.62-4.47(m,4H),4.42(t,J=6. 1Hz,2H),3.85(s,3H),2.84(t,J=7.4Hz,2H),2.62(t,J=7.4Hz,2H),2.26(bs,4H).

[0446] Example 15 Synthesis of 7-methoxy-3-(6-{1-[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-imidazo[1,2-a]pyridine ("A171") [ka] White solid; mp195~196℃; HPLC / MS[M+H] + 427. 1H NMR(300MHz,DMSO-d6)δ9.73(d,J=7.7Hz,1H),8.77(d,J=1.1Hz,1H),8.49(s ,1H),8.10(s,1H),7.82(d,J=0.8Hz,1H),7.54(d,J=8.3Hz,2H),7.46(d,J=1. 2Hz,1H),7.43(d,J=8.3Hz,2H),7.14(d,J=2.6Hz,1H),6.86(dd,J=7.7,2.7Hz ,1H),6.27(q,J=6.5Hz,1H),3.88(s,3H),3.85(s,3H),1.63(d,J=6.5Hz,3H).

[0447] Example 16 Synthesis of 2-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)ethan-1-ol ("A172") [ka] From G1 and E25. The synthesis is carried out analogously to Example 2. Before work-up, the reaction mixture is treated with aqueous 1N hydrochloric acid and stirred at room temperature for 3 hours; white solid; HPLC / MS (B) 0.686 min, [M+H] + 442. 1 H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.7Hz ,1H),7.83(t,J=6.1Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz ,2H),7.07(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.81(dd,J=7.7,2.6Hz,1H),4.90(t,J =5.5Hz,1H),4.60-4.51(m,2H),4.11(t,J=4.8Hz,2H),3.84(s,3H),3.76(q,J=5.1Hz,2H).

[0448] The following compounds are prepared analogously: 2-({3-[6-({[4-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)ethan-1-ol ("A173") [ka] From G3 and E25; off-white powder; UPLC / MS 0.443 min, [M+H] + 443. 1 H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(d,J=1.2Hz,1H),8.16(s,1H),8 .15(s,1H),7.88(t,J=6.2Hz,1H),7.79(d,J=8.3Hz,2H),7.44(d,J=7.9Hz,2H),7.07 (d,J=2.6Hz,1H),6.90(d,J=1.2Hz,1H),6.81(dd,J=7.7,2.6Hz,1H),4.90(t,J=5.4H z,1H),4.64-4.38(m,2H),4.17(s,4H),4.11(t,J=4.8Hz,2H),3.76(q,J=5.0Hz,2H).

[0449] Example 17 Synthesis of [5-(4-{[6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-ylamino]-methyl}-phenyl)-1-methyl-1H-imidazol-2-yl]-methanol ("A174") [ka] Yellow solid;mp255~256℃;HPLC / MS[M+H] + 442. 1H NMR(400MHz,DMSO-d6)δ9.71(d,J=7.7Hz,1H),8.53(s,1H),8.18(s,1H),7.96(t,J=6.2Hz,1H),7.56-7.38(m,4H),7.10(d,J=2.6Hz,1H),6.93( d,J=1.2Hz,1H),6.91(s,1H),6.81(dd,J=7.7,2.7Hz,1H),5.32(t,J=5.5Hz,1H),4.62(s,2H),4.53(d,J=5.5Hz,2H),3.88(s,3H),3.63(s,3H).

[0450] Example 18 Synthesis of [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(2-pyrrolidin-3-yl-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A175") [ka] White solid;mp278~279℃;HPLC / MS[M+H] + 495. 1 H NMR(300MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.40(s,1H),8.25-8.12(m,1H),8.08(s,1H),7.89(t, J=6.1Hz,1H),7.81(s,1H),7.58-7.47(m,2H),7.34(d,J=7.9Hz,2H),7.10(d,J=2.6Hz,1H),6.89(d,J=1.3Hz,1H) ,6.79(dd,J=7.8,2.5Hz,1H),4.67-4.48(m,2H),4.13(t,J=6.4Hz,2H),3.32-3.21(m,1H),3.21-3.08(m,1H),3.0 8-2.93(m,1H),2.77-2.66(m,1H),2.38-2.23(m,1H),2.11-2.01(m,1H),1.87(d,J=7.1Hz,2H),1.62-1.43(m,1H).

[0451] The following compounds are prepared analogously: [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-{6-[7-(2-pyrrolidin-3-yl-ethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A176") [ka] From H2; White solid; HPLC / MS [M+H] + 496. 1 H NMR(300MHz,DMSO-d6)δ9.69(d,J=7.5Hz,1H),8.50(s,1H),8.17(s,2H),7.96(s,1H),7.78(d,J=7.9Hz,2H),7.42(d,J=7.9Hz) ,2H),7.06-6.75(m,3H),4.58(s,2H),4.14(d,J=14.5Hz,5H),2.71(s,1H),2.30(s,2H),1.95(d,J=55.5Hz,3H),1.52(s,1H).

[0452] Example 19 Synthesis of [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-[6-(7-pyrrolidin-1-yl-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-amine ("A177") [ka] To a suspension of 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine (H1) (79.9 mg, 0.20 mmol) in toluene (3 ml), pyrrolidine (21.3 mg, 0.30 mmol) and 1,3-dimethyl-1,3-diazinan-2-one (dimethylpropyleneurea, DMPU, 77 mg, 0.60 mmol) were added, and the reaction mixture was stirred for 16 hours at 110° C. After the reaction mixture reached room temperature, it was evaporated under vacuum. The residue was chromatographed on a silica gel column using dichloromethane / methanol as eluent to give N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-[7-(pyrrolidin-1-yl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine as a yellow solid; mp 241-242°C; HPLC / MS [M+H] + 451. 1 H NMR(400MHz,DMSO-d6)δ9.59(d,J=7.8Hz,1H),8.48(s,1H),8.08(s,1H),7. 81(s,1H),7.78(t,J=6.1Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.9Hz,2 H),6.82(d,J=1.2Hz,1H),6.71(dd,J=7.8,2.5Hz,1H),6.38(d,J=2.4Hz,1H ),4.52(d,J=5.9Hz,2H),3.84(s,3H),3.42-3.31(m,4H),2.06-1.91(m,4H).

[0453] The following compounds are prepared analogously: 2-[1-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yl)-pyrrolidin-3-yl]-ethanol ("A178") [ka] From H1; White solid; mp251~252℃; HPLC / MS (B) 0.720min, [M+H] + 495. 1 H NMR(500MHz,DMSO-d6)δ9.58(d,J=7.7Hz,1H),8.46(d,J=1.1Hz,1H),8.07(s,1H),8.00(s,1H),7.80(d,J=0.8Hz,1H ),7.69(t,J=6.1Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),6.79(s,1H),6.65(dd,J=7.8,2.5Hz,1H),6.35 (d,J=2.4Hz,1H),4.52(d,J=6.1Hz,2H),4.45(t,J=5.1Hz,1H),3.84(s,3H),3.59-3.47(m,3H),3.43(td,J=9.2,8.3, 3.0Hz,1H),3.32(dd,J=9.6,7.4Hz,1H),3.00-2.94(m,1H),2.43-2.32(m,1H),2.23-2.08(m,1H),1.72-1.53(m,3H).

[0454] 2-[1-(3-{6-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yl)-pyrrolidin-3-yl]-ethanol ("A179") [ka] From H2; Light brown solid; MP 200-201°C; HPLC / MS [M+H] + 496. 1H NMR(300MHz,DMSO-d6)δ9.57(d,J=7.8Hz,1H),8.45(s,1H),8.16(s,1H),8.01(s,1H),7.77(d,J=8.1Hz,3H),7.42(d,J=8.1Hz,2H),6.79(s ,1H),6.64(d,J=6.3Hz,1H),6.34(s,1H),4.61-4.44(m,3H),4.16(s,3H),3.48(q,J=6.7Hz,4H),2.99-2.91(m,1H),1.58(d,J=6.9Hz,3H).

[0455] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-[6-(7-morpholin-4-yl-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-amine ("A180") [ka] From H1; Yellow solid; mp241~242℃; HPLC / MS [M+H] + 467. 1 H NMR(400MHz,DMSO-d6)δ9.61(d,J=7.8Hz,1H),8.49(s,1H),8.12-8.05(m,3H),7.83-7.75(m,3H),7.51(d,J=8.2Hz,2H),7.34(d,J= 7.9Hz,2H),7.01(dd,J=7.9,2.6Hz,1H),6.88-6.80(m,2H),4.53(s,2H),3.84(s,3H),3.76(t,J=4.8Hz,4H),3.26(t,J=5.0Hz,4H).

[0456] {6-[7-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A181") [ka] From H1; White solid; MP 252-253°C; HPLC / MS [M+H] + 480. 1 H NMR(400MHz,DMSO-d6)δ9.58(d,J=7.8Hz,1H),8.49(s,1H),8.08(s,2H),7.83-7.75(m,2H),7.51(d,J=8.1Hz,2H),7.34(d,J=7.9Hz,2 H),7.00(dd,J=8.0,2.6Hz,1H),6.86-6.77(m,2H),4.57-4.48(m,2H),3.84(s,3H),3.30-3.25(m,4H),2.48-2.45(m,4H),2.24(s,3H).

[0457] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(4-oxetan-3-yl-piperazin-1-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A230") [ka]

[0458] [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-[6-(7-pyrrolidin-1-yl-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-amine ("A232") [ka]

[0459] Example 20 Synthesis of N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-(7-{[1-(oxetan-3-yl)piperidin-4-yl]oxy}imidazo[1,2-a]pyridin-3-yl)pyrimidin-4-amine ("A182") [ka] From "A164"; Off-white solid; HPLC / MS (B) 0.635min, [M+H] + 537. 1H NMR(500MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.13(s,1H),8.07(d,J=0.8Hz,1H),7.82(t,J=6.1Hz,1H ),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.8Hz,2H),7.13(d,J=2.6Hz,1H),6.88(d,J=1.2Hz,1H), 6.79(dd,J=7.7,2.6Hz,1H),4.60(tt,J=7.9,3.9Hz,1H),4.54(t,J=6.5Hz,4H),4.43(t,J=6.1Hz,2H),3.84(s,3H), 3.43(p,J=6.4Hz,1H),2.58-2.51(m,2H),2.19-2.12(m,2H),2.06-1.97(m,2H),1.70(dtt,J=12.3,8.6,3.5Hz,2H).

[0460] The following compounds are prepared analogously: N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-(7-{[1-(oxetan-3-yl)azetidin-3-yl]methoxy}imidazo[1,2-a]pyridin-3-yl)pyrimidin-4-amine ("A183") [ka] From "A167"; Off-white powder; UPLC / MS 0.367 min, [M+H] + 523. 1H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.52(s,1H),8.15(s,1H),8.08(s,1H),7.84(t,J=6.1Hz,1H),7 .81(d,J=0.8Hz,1H),7.52(d,J=8.2Hz,2H),7.35(d,J=7.8Hz,2H),7.10(d,J=2.6Hz,1H),6.90(d,J=1.3Hz,1H) ,6.81(dd,J=7.7,2.6Hz,1H),4.62-4.51(m,5H),4.39(dd,J=6.4,5.3Hz,2H),4.25(d,J=6.8Hz,2H),3.85(s,3H) ),3.72(tt,J=6.8,5.2Hz,1H),3.39(t,J=7.4Hz,2H),3.10(dd,J=7.1,5.8Hz,2H),2.89(tt,J=7.6,6.0Hz,1H).

[0461] Example 21 Synthesis of [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-(6-{7-[3-(4-oxetan-3-yl-piperazin-1-yl)-propoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A184") [ka] From "A131"; yellow solid; mp 300-301°C; HPLC / MS [M+H] + 580. 1H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.08(s,1H),7.85(t,J=6.1H) z,1H),7.81(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.9Hz,2H),7.05(d,J=2.6Hz,1H),6.8 9(d,J=1.2Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.59-4.47(m,4H),4.41(t,J=6.1Hz,2H),4.12(t,J=6 .3Hz,2H),3.84(s,3H),3.38(p,J=6.3Hz,1H),2.49-2.39(m,6H),2.27(bs,4H),1.91(p,J=6.6Hz,2H).

[0462] The following compounds are prepared analogously: [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-(6-{7-[3-(4-oxetan-3-yl-piperazin-1-yl)-propoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A185") [ka] From "A134"; White solid; MP 225-226°C; HPLC / MS [M+H] + 581. 1H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.8Hz,1H),8.50(s,1H),8.15(d,J=7.2Hz,2H),7.89(t,J=6.2Hz,1 H),7.77(d,J=8.1Hz,2H),7.42(d,J=8.0Hz,2H),7.04(d,J=2.7Hz,1H),6.89(d,J=1.3Hz,1H),6.77(d d,J=7.7,2.6Hz,1H),4.58(d,J=6.2Hz,2H),4.50(t,J=6.5Hz,2H),4.39(t,J=6.0Hz,2H),4.16(s,3H) ,4.10(t,J=6.3Hz,2H),3.37(q,J=6.4Hz,1H),2.47-2.38(m,6H),2.25(s,4H),1.89(t,J=6.7Hz,2H).

[0463] Example 22 Synthesis of {6-[7-(1-cyclopropyl-piperidin-4-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A186") [ka] From "A165"; White solid; MP 238-240°C; HPLC / MS [M+H] + 536. 1 H NMR(400MHz,DMSO-d6ppm)9.73-9.63(m,1H),8.51(s,1H),8.20-8.09(m,2H),7.92-7.88(m,1H) ,7.82-7.75(m,2H),7.47-7.39(m,2H),7.06-7.02(m,1H),6.90(s,1H),6.83-6.75(m,1H),4.63- 4.54(m,2H),4.17(s,3H),3.97-3.89(m,2H),3.00-2.90(m,2H),2.22-2.10(m,2H),1.84-1.69( m,3H),1.61-1.55(m,1H),1.26(s,1H),1.24-1.17(m,2H),0.43-0.36(m,2H),0.31-0.24(m,2H).

[0464] The following compounds are prepared similarly: {6-[7-(1-cyclopropyl-piperidin-4-ylmethoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A187") [ka] From "A166"; White solid; MP 236-238°C; HPLC / MS [M+H] + 535. 1 H NMR(400MHz,DMSO-d6)δ9.70-9.66(m,1H),8.51(s,1H),8.17-8.05(m,2H),7.89-7.78(m,2H) ,7.53-7.45(m,2H),7.38-7.29(m,2H),7.06-7.02(m,1H),6.90-6.85(m,1H),6.83-6.76(m,1H ),4.59-4.44(m,2H),3.97-3.89(m,2H),3.84(s,3H),3.00-2.89(m,2H),2.21-2.10(m,2H),1 .84-1.70(m,3H),1.61-1.53(m,1H),1.27-1.18(m,2H),0.44-0.36(m,2H),0.29-0.23(m,2H).

[0465] Example 23 Synthesis of [4-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxymethyl)-piperidin-1-yl]-acetonitrile ("A188") [ka] From "A166"; White solid; MP 211-212°C; HPLC / MS [M+H] + 534. 1H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.19-8.12(m,1H),8.08(s,1H),7.85(t, J=6.1Hz,1H),7.81(s,1H),7.51(d,J=8.1Hz,2H),7.34(d,J=8.0Hz,2H),7.07(d,J=2.6Hz,1H),6.89 (s,1H),6.80(dd,J=7.8,2.6Hz,1H),4.61-4.50(m,2H),3.96(d,J=5.8Hz,2H),3.84(s,3H),3.71(s, 2H),2.83(d,J=10.8Hz,2H),2.19(t,J=11.2Hz,2H),1.82(d,J=12.7Hz,3H),1.36(d,J=13.0Hz,2H).

[0466] The following compounds are prepared similarly: [4-(3-{6-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxymethyl)-piperidin-1-yl]-acetonitrile ("A189") [ka] From "A165"; White solid; MP 265-266°C; HPLC / MS [M+H] + 535. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.50(s,1H),8.15(d,J=6.9Hz,2H),7.90(t,J=6 .1Hz,1H),7.77(d,J=8.0Hz,2H),7.42(d,J=7.9Hz,2H),7.05(d,J=2.6Hz,1H),6.89(s,1H),6.7 9(dd,J=7.7,2.6Hz,1H),4.58(d,J=6.0Hz,2H),4.16(s,3H),3.94(d,J=5.7Hz,2H),3.69(s,2H) ,2.82(d,J=10.8Hz,2H),2.17(t,J=11.1Hz,2H),1.80(d,J=12.3Hz,3H),1.34(d,J=12.9Hz,2H)

[0467] [4-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxymethyl)-piperidin-1-yl]-acetonitrile ("A190") [ka] From "A166" and 1-bromo-2-methoxyethane; white solid; mp 255-256°C; HPLC / MS [M+H] + 553. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.26-8.11(m,1H),8.08(s,1H),7.85(t,J=6.1 Hz,1H),7.81(s,1H),7.51(d,J=7.9Hz,2H),7.34(d,J=7.8Hz,2H),7.05(d,J=2.6Hz,1H),6.89(s,1H),6.79 (dd,J=7.7,2.6Hz,1H),4.66-4.48(m,2H),3.94(d,J=5.9Hz,2H),3.84(s,3H),3.42(t,J=5.9Hz,2H),2.89( d,J=11.0Hz,2H),2.45(t,J=6.0Hz,2H),1.96(t,J=11.3Hz,2H),1.74(d,J=11.6Hz,3H),1.41-1.25(m,2H).

[0468] (6-{7-[1-(2-methoxy-ethyl)-piperidin-4-ylmethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A191") [ka] "A165" and 1-bromo-2-methoxyethane; white solid; mp 270-271°C; HPLC / MS [M+H] + 554. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.50(s,1H),8.15(d,J=7.9Hz,2H),7.89(t,J=6.1Hz, 1H),7.77(d,J=8.2Hz,2H),7.42(d,J=7.9Hz,2H),7.04(d,J=2.6Hz,1H),6.89(s,1H),6.78(dd,J=7.8 ,2.6Hz,1H),4.58(d,J=5.9Hz,2H),4.16(s,3H),3.93(d,J=5.9Hz,2H),3.41(t,J=5.9Hz,2H),2.89( d,J=10.9Hz,2H),2.45(s,2H),1.97(t,J=11.6Hz,2H),1.73(d,J=11.0Hz,3H),1.30(d,J=11.9Hz,2H)

[0469] (6-{7-[1-(2,2-difluoro-ethyl)-piperidin-4-ylmethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A192") [ka] From "A166" and 1,1-difluoro-2-iodoethane; white solid; mp 215-216°C; HPLC / MS [M+H] + 559. 1H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.49(s,1H),8.09(d,J=18.3Hz,2H),7.89-7.76(m,2H) ,7.50(d,J=8.1Hz,2H),7.32(d,J=7.9Hz,2H),7.04(d,J=2.7Hz,1H),6.87(d,J=1.3Hz,1H),6.78(dd,J =7.7,2.6Hz,1H),6.11(t,J=4.3Hz,1H),4.52(s,2H),3.93(d,J=5.9Hz,2H),3.83(s,3H),2.91(d,J=1 1.0Hz,2H),2.75-2.62(m,2H),2.15(t,J=11.4Hz,2H),1.73(d,J=12.3Hz,3H),1.32(q,J=11.3Hz,2H).

[0470] (6-{7-[1-(2,2-difluoro-ethyl)-piperidin-4-ylmethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A193") [ka] From "A165" and 1,1-difluoro-2-iodoethane; white solid; mp 255-256°C; HPLC / MS [M+H] + 560. 1H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.50(s,1H),8.15(d,J=7.6Hz,2H),7.90(t,J=6.2Hz,1H) ,7.77(d,J=8.1Hz,2H),7.42(d,J=7.9Hz,2H),7.04(d,J=2.6Hz,1H),6.89(d,J=1.2Hz,1H),6.78(dd,J= 7.7,2.6Hz,1H),6.14-5.88(m,1H),4.58(d,J=5.9Hz,2H),4.16(s,3H),3.93(d,J=5.9Hz,2H),2.91(d,J =11.0Hz,2H),2.69(td,J=15.6,4.3Hz,2H),2.21-2.10(m,2H),1.73(d,J=11.4Hz,3H),1.40-1.27(m,2H)

[0471] Example 24 Synthesis of [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-(6-{7-[2-(1-oxo-114-thiomorpholin-4-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A194") [ka] From "A172": To a suspension of 2-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)ethan-1-ol (10.0 g, 22.6 mmol) in DMF (150 ml) is added triphenylphosphine (8.91 g, 34.0 mmol). The mixture is then cooled in a cold water bath while carbon tetrabromide (11.27 g, 34.0 mmol) is added portionwise with stirring over a period of 20 min. The reaction mixture is stirred at room temperature for 18 h. The solvent is removed under reduced pressure. The residue is triturated with diethyl ether and ethyl acetate. The resulting solid is chromatographed on a silica gel column using methanol / chloroform as eluent to give 6-[7-(2-bromoethoxy)imidazo[1,2-a]pyridin-3-yl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine as a white solid.

[0472] A reaction vial was charged with 6-[7-(2-bromoethoxy)imidazo[1,2-a]pyridin-3-yl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine (50.0 mg, 0.1 mmol), the corresponding amine (0.2 mmol), and DMF (0.3 ml), and the mixture was heated at 90° C. for 18 hours. After the reaction mixture reached room temperature, it was evaporated. The residue was purified by preparative HPLC using methanol / aqueous ammonia as the eluent.

[0473] The following compounds are prepared analogously: (6-{7-[2-(1,3-dihydro-pyrrolo[3,4-c]pyridin-2-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A195") [ka]

[0474] (6-{7-[2-(4-fluoro-4-methyl-piperidin-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A196") [ka]

[0475] (6-{7-[2-(4-cyclopropyl-piperazin-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A197") [ka]

[0476] (6-{7-[2-(3-methyl-3,8-diaza-bicyclo[3.2.1]oct-8-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A198") [ka]

[0477] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-(6-{7-[2-(2-oxo-214-thia-5-aza-bicyclo[2.2.1]hept-5-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A199") [ka]

[0478] (6-{7-[2-(6,6-difluoro-[1,4]oxazepan-4-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A200") [ka]

[0479] (6-{7-[2-(hexahydro-pyrazino[2,1-c][1,4]oxazin-8-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A201") [ka]

[0480] (6-{7-[2-(4,4-difluoro-piperidin-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A202") [ka]

[0481] (6-{7-[2-(5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A203") [ka]

[0482] (6-{7-[2-(2-methyl-5,6-dihydro-8H-[1,2,4]triazolo[1,5-a]pyrazin-7-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A204") [ka]

[0483] {Methyl-[2-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxy)-ethyl]-amino}-acetonitrile ("A205") [ka]

[0484] [3-methyl-1-[2-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxy)-ethyl]-azetidine-3-carbonitrile ("A206") [ka]

[0485] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-(6-{7-[2-(6-oxa-1-aza-spiro[3.3]hept-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A207") [ka]

[0486] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-[6-(7-{2-[methyl-(2,2,2-trifluoro-ethyl)-amino]-ethoxy}-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-amine ("A208") [ka]

[0487] (6-{7-[2-((3S,4R)-3,4-difluoro-pyrrolidin-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A209") [ka]

[0488] (6-{7-[(3aS,7aS)-2-(hexahydro-furo[3,2-b]pyridin-4-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A210") [ka]

[0489] (6-{7-[(4aS,8aS)-2-(hexahydro-pyrano[3,4-b][1,4]oxazin-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A211") [ka]

[0490] (6-{7-[2-(1,4-diaza-bicyclo[3.2.1]oct-4-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A212") [ka]

[0491] [6-(7-{2-[3-(3-methyl-[1,2,4]oxadiazol-5-yl)-azetidin-1-yl]-ethoxy}-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-yl]-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A213") [ka]

[0492] (6-{7-[2-(2,2-difluoro-morpholin-4-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A214") [ka]

[0493] (6-{7-[2-(3-methanesulfonyl-azetidin-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A215") [ka]

[0494] (6-{7-[2-(6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A216") [ka]

[0495] (6-{7-[2-(6,7-dihydro-4H-[1,2,3]triazolo[1,5-a]pyrazin-5-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A217") [ka] Light brown solid; HPLC / MS(B):1.18min[M+H] + =548. 1 H NMR(500MHz,DMSO-d6)δ9.73-9.65(m,1H),8.50(s,1H),8.15(s,1H),8.08(s,1H),7.86(t,J= 6.1Hz,1H),7.81(d,J=0.8Hz,1H),7.56-7.48(m,3H),7.34(d,J=7.8Hz,2H),7.14(d,J=2.7Hz, 1H),6.92-6.87(m,1H),6.82(dd,J=7.7,2.6Hz,1H),4.52(s,2H),4.37(t,J=5.6Hz,2H),4.30( t,J=5.5Hz,2H),3.88(s,2H),3.84(s,3H),3.09(dd,J=6.2,5.0Hz,2H),3.03(t,J=5.5Hz,2H).

[0496] (6-{7-[2-(3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-2-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A218") [ka]

[0497] 4-Methyl-1-[2-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxy)-ethyl]-[1,4]diazepan-5-one ("A219") [ka]

[0498] (6-{7-[2-(4-methoxy-4-methyl-piperidin-1-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A220") [ka]

[0499] (6-{7-[2-(3-methyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-ethoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A221") [ka]

[0500] 4-Methyl-1-[2-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxy)-ethyl]-piperidine-4-carbonitrile ("A222") [ka]

[0501] 7-methyl-2-[2-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yloxy)-ethyl]-5-oxa-2,7-diaza-spiro[3.4]octan-6-one ("A248") [ka]

[0502] Example 25 Synthesis of {6-[7-(4-azetidin-1-yl-butoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A225") [ka] White solid;mp187~195℃;HPLC / MS[M+H] + 509. 1 H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.49(s,1H),8.10(d,J=17.9Hz,2H),7.83(d,J= 19.4Hz,2H),7.50(d,J=8.0Hz,2H),7.32(d,J=7.9Hz,2H),7.05(d,J=2.6Hz,1H),6.87(s,1H),6 .77(dd,J=7.7,2.6Hz,1H),4.52(s,2H),4.05(t,J=6.5Hz,2H),3.83(s,3H),3.06(t,J=6.9Hz, 4H),2.36(t,J=7.1Hz,2H),1.92(p,J=6.9Hz,2H),1.73(t,J=7.4Hz,2H),1.40(q,J=7.3Hz,2H).

[0503] Example 26 Synthesis of 6-[7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A226") [ka] Yellow solid; HPLC / MS(B)0.741min, [M+H] + 462. 1 H NMR(500MHz,DMSO-d6)δ9.77(dd,J=7.3,0.9Hz,1H),8.55(s,1H),8.35(s,1H),8.24(s,1H),8.07(d,J=0.8Hz,2H),7.89-7.85(m,2H) ,7.80(d,J=0.9Hz,1H),7.55-7.49(m,3H),7.38-7.30(m,4H),6.94(d,J=1.2Hz,1H),4.55(d,J=5.9Hz,2H),3.89(s,3H),3.84(s,3H).

[0504] Example 27 Synthesis of {6-[7-(2-methyl-3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A227") [ka] White solid;mp230~231℃;HPLC / MS[M+H] + 524. 1 H NMR(300MHz,DMSO-d6)δ9.68(d,J=7.7Hz,1H),8.50(s,1H),8.15(d,J=7.5Hz,2H),7.90( t,J=6.2Hz,1H),7.82-7.73(m,2H),7.42(d,J=7.9Hz,2H),7.04(d,J=2.6Hz,1H),6.89(d, J=1.2Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.58(d,J=6.0Hz,2H),4.16(s,3H),4.04(dd,J =9.7,4.7Hz,1H),3.94(t,J=7.8Hz,1H),2.13(s,1H),1.69(s,4H),1.02(d,J=6.6Hz,3H).

[0505] The following compounds are prepared analogously: [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(2-methyl-3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A235") [ka] White solid;mp217~220℃;HPLC / MS[M+H] + 523. 1 H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.49(s,1H),8.10(d,J=19.0Hz,2H),7.82(d,J=15.6Hz,2H),7. 50(d,J=8.1Hz,2H),7.32(d,J=7.9Hz,2H),7.03(d,J=2.5Hz,1H),6.87(d,J=1.2Hz,1H),6.78(dd,J=7.7,2.6H z,1H),4.52(d,J=5.9Hz,2H),4.04(dd,J=9.6,4.7Hz,1H),3.92(dd,J=9.6,6.2Hz,1H),3.83(s,3H),2.53(s,1 H),2.43(s,4H),2.29(dd,J=11.9,7.3Hz,1H),2.16-2.04(m,1H),1.66(d,J=6.8Hz,4H),1.01(d,J=6.6Hz,3H).

[0506] Example 28 Synthesis of 1-[3-({3-[6-({[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}amino)pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl}oxy)propyl]pyrrolidin-1-ium-1-olate ("A228") [ka] From "A75" [ka] Gray-white solid; HPLC / MS (B) 0.651min, [M+2H] 2+ / 2 263. 1 H NMR(500MHz,DMSO-d6)δ9.70(d,J=7.7Hz,1H),8.51(s,1H),8.14(s,1H),8.07(d,J=0.8Hz,1H),7.85(t,J=6 .1Hz,1H),7.80(d,J=0.8Hz,1H),7.51(d,J=8.2Hz,2H),7.34(d,J=7.7Hz,2H),7.08(d,J=2.6Hz,1H),6.89(d ,J=1.3Hz,1H),6.79(dd,J=7.7,2.6Hz,1H),4.54(d,J=6.0Hz,2H),4.25(t,J=6.3Hz,2H),3.84(s,3H),3.39- 3.34(m,2H),3.34-3.29(m,2H),3.15-3.07(m,2H),2.41-2.32(m,2H),2.25-2.11(m,2H),1.90-1.78(m,2H).

[0507] Example 29 Synthesis of 1-[3-amino-4-(4-{[6-(7-methoxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-4-ylamino]-methyl}-phenyl)-pyrazol-1-yl]-2-methyl-propan-2-ol ("A229") [ka] White solid;mp298~299℃;HPLC / MS[M+H] + 485. 1H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.6Hz,1H),8.51(s,1H),8.16(s,1H),7.90( t,J=6.1Hz,1H),7.65(s,1H),7.48-7.41(m,2H),7.32(d,J=7.7Hz,2H),7.09(d ,J=2.7Hz,1H),6.89(d,J=1.2Hz,1H),6.81(dd,J=7.7,2.6Hz,1H),4.70(s,1H) ,4.66(s,2H),4.53(s,2H),3.87(s,3H),3.77(s,2H),1.14(s,1H),1.06(s,6H).

[0508] Example 30 Synthesis of [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-(6-{7-[3-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-propoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A238") [ka] White solid;mp175~180℃;HPLC / MS[M+H] + 537. 1 H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.49(s,1H),8.10(d,J=18.1Hz ,2H),7.87(t,J=6.1Hz,1H),7.80(s,1H),7.50(d,J=8.1Hz,2H),7.32(d,J=7. 8Hz,2H),7.03(d,J=2.6Hz,1H),6.87(d,J=1.2Hz,1H),6.76(dd,J=7.7,2.6Hz ,1H),4.58(s,6H),4.05(t,J=6.3Hz,2H),3.83(s,3H),1.72(t,J=6.6Hz,2H).

[0509] The following compounds are prepared analogously: [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-(6-{7-[3-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-propoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-amine ("A239") [ka] White solid;mp230~231℃;HPLC / MS[M+H] + 538. 1 H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.49(s,1H),8.15(d,J=8.1Hz, 2H),7.90(t,J=6.1Hz,1H),7.82-7.73(m,2H),7.42(d,J=7.9Hz,2H),7.02(d, J=2.6Hz,1H),6.88(d,J=1.2Hz,1H),6.76(dd,J=7.7,2.6Hz,1H),4.57(s,6H) ,4.16(s,3H),4.05(t,J=6.3Hz,2H),2.42(t,J=6.9Hz,2H),1.75-1.63(m,2H).

[0510] (6-{7-[3-(3-fluoro-azetidin-1-yl)-propoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A240") [ka] White solid;mp190~195℃;HPLC / MS[M+H] + 513. 1H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.49(s,1H),8.10(d,J=18.3Hz,2H),7.91-7.7 7(m,2H),7.50(d,J=8.1Hz,2H),7.32(d,J=7.9Hz,2H),7.03(d,J=2.6Hz,1H),6.87(d,J=1.2H z,1H),6.77(dd,J=7.7,2.6Hz,1H),5.22-5.00(m,1H),4.52(s,2H),4.07(t,J=6.3Hz,2H),3. 82(s,3H),3.63-3.47(m,2H),3.14-2.95(m,2H),2.57(t,J=6.9Hz,2H),1.75(t,J=6.6Hz,2H).

[0511] [4-(1-メチル-1H-ピラゾール-4-イル)-ベンジル]-(6-{7-[3-(1-オキソ-1l4-チオモルホリン-4-イル)-プロポキシ]-イミダゾ[1,2-a]ピリジン-3-イル}-ピリミジン-4-イル)-アミン(「A241」)

change

[0512] [4-(2-Methyl-oxazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A242") [ka] From intermediate H4; white solid; mp 288-289°C; HPLC / MS [M+H] + 510. 1 H NMR(400MHz,DMSO-d6)δ9.69(d,J=7.7Hz,1H),8.51(s,1H),8.42(s,1H),8.19-8.1 0(m,1H),7.90(t,J=6.2Hz,1H),7.76-7.67(m,2H),7.40(d,J=7.6Hz,2H),7.06(d,J =2.7Hz,1H),6.89(s,1H),6.80(dd,J=7.7,2.6Hz,1H),4.57(s,2H),4.12(t,J=6.3H z,2H),2.58-2.52(m,2H),2.49-2.39(m,7H),1.98-1.88(m,2H),1.74-1.62(m,4H).

[0513] (6-{7-[3-(4-cyclopropyl-piperazin-1-yl)-propoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine ("A243") [ka] Pale yellow solid; mp215~219℃; HPLC / MS[M+H] + 564. 1H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.49(s,1H),8.10(d,J=19.4Hz,2H),7.86(t,J=6.2Hz,1H),7 .80(d,J=0.8Hz,1H),7.54-7.45(m,2H),7.32(d,J=7.8Hz,2H),7.04(d,J=2.6Hz,1H),6.87(d,J=1.2Hz,1H), 6.77(dd,J=7.7,2.6Hz,1H),4.52(d,J=5.8Hz,2H),4.09(t,J=6.3Hz,2H),3.82(s,3H),2.38(dd,J=17.6,10. 4Hz,6H),1.89(q,J=6.7Hz,2H),1.55(dq,J=6.7,3.3Hz,1H),0.36(dt,J=6.0,2.9Hz,2H),0.28-0.19(m,2H).

[0514] {6-[7-(3-Azetidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-{1-[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-ethyl}-amine ("A249") [ka] From H5; White solid; HPLC / MS [M+H] + 509.

[0515] {1-[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-ethyl}-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A250") [ka] From H5; White solid; HPLC / MS [M+H] + 523.

[0516] (6-{7-[3-(4-cyclopropyl-piperazin-1-yl)-propoxy]-imidazo[1,2-a]pyridin-3-yl}-pyrimidin-4-yl)-[4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-amine ("A253") [ka] From H2; pale yellow solid; mp 225-226°C; HPLC / MS [M+H] + 565. 1 H NMR(300MHz,DMSO-d6)δ9.67(d,J=7.7Hz,1H),8.50(s,1H),8.16(s,2H),7.91(t,J=6.2Hz,1H),7.8 2-7.73(m,2H),7.42(d,J=7.8Hz,2H),7.04(d,J=2.6Hz,1H),6.89(d,J=1.3Hz,1H),6.77(dd,J=7.7, 2.6Hz,1H),4.57(d,J=6.0Hz,2H),4.16(s,3H),4.09(t,J=6.3Hz,2H),2.38(dd,J=17.3,10.2Hz,6H) ,1.88(t,J=6.9Hz,2H),1.55(tt,J=6.5,3.5Hz,1H),0.36(dt,J=6.1,2.8Hz,2H),0.33-0.19(m,2H).

[0517] Example 31 Synthesis of [4-(2-methyl-2H-[1,2,3]triazol-4-yl)-benzyl]-{6-[7-(4-oxetan-3-yl-piperazin-1-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A244") [ka] White solid;mp300℃;HPLC / MS[M+H] + 523. 1H NMR(300MHz,DMSO-d6)δ9.58(d,J=7.8Hz,1H),8.48(s,1H),8.16(s,1H),8. 08(s,1H),7.85(t,J=6.1Hz,1H),7.77(d,J=8.1Hz,2H),7.42(d,J=7.9Hz,2H ),7.00(dd,J=7.9,2.5Hz,1H),6.87-6.76(m,2H),4.56(t,J=6.4Hz,4H),4.4 6(t,J=6.0Hz,2H),4.16(s,3H),3.44(t,J=6.2Hz,1H),2.40(d,J=5.4Hz,4H)

[0518] The following compounds are prepared analogously: 1-(3-{6-[4-(1-methyl-1H-pyrazol-4-yl)-benzylamino]-pyrimidin-4-yl}-imidazo[1,2-a]pyridin-7-yl)-pyrrolidin-3-ol ("A245") [ka] White solid;mp282~283℃;HPLC / MS[M+H] + 467. 1 H NMR(400MHz,DMSO-d6)δ9.59(d,J=7.8Hz,1H),8.46(s,1H),8.08(s,1H),8.05-7.96(m,1H),7.81(s,1H), 7.75(t,J=6.2Hz,1H),7.51(d,J=8.0Hz,2H),7.33(d,J=7.8Hz,2H),6.80(s,1H),6.66(dd,J=7.8,2.5Hz,1 H),6.36(d,J=2.4Hz,1H),5.04(d,J=3.7Hz,1H),4.57-4.47(m,2H),4.45-4.40(m,1H),3.84(s,3H),3.49 (dd,J=10.6,4.7Hz,1H),3.46-3.37(m,2H),3.20(d,J=10.0Hz,1H),2.13-2.00(m,1H),1.95-1.91(m,1H).

[0519] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A246") [ka] White solid;mp292~293℃;HPLC / MS[M+H] + 479. 1 H NMR(400MHz,DMSO-d6)δ9.61(d,J=7.6Hz,1H),8.47(s,1H),8.09-8.02(m,2H),7.83-7.74(m,2H),7.54-7.48(m,2H),7.33(d,J=7.9 Hz,2H),6.81(s,1H),6.47(dd,J=7.6,2.4Hz,1H),6.35(d,J=2.4Hz,1H),4.73(s,4H),4.56-4.47(m,2H),4.12(s,4H),3.84(s,3H).

[0520] [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(2-oxa-6-aza-spiro[3.4]oct-6-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine ("A247") [ka] White solid;mp284~285℃;HPLC / MS[M+H] + 493. 1H NMR(400MHz,DMSO-d6)δ9.61(d,J=7.7Hz,1H),8.48(s,1H),8.09(s,1H),8.07-7.99(m ,1H),7.82(s,1H),7.77(t,J=6.1Hz,1H),7.52(d,J=8.1Hz,2H),7.39-7.29(m,2H),6. 81(s,1H),6.68(dd,J=7.9,2.5Hz,1H),6.40(d,J=2.4Hz,1H),4.61(d,J=6.0Hz,2H),4 .58-4.43(m,4H),3.85(s,3H),3.63(s,2H),3.40-3.35(m,2H),2.30(t,J=6.9Hz,2H).

[0521] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-[7-(1H-1,2,4-triazol-1-yl)imidazo[1,2-a]pyridin-3-yl]pyrimidin-4-amine ("A266") [ka] From H1; White solid; MP 272-273°C; HPLC / MS [M+H] + 449. 1 H NMR(400MHz,DMSO-d6)δ9.93(d,J=7.7Hz,1H),9.48(s,1H),8.55(s,1H),8 .40-8.28(m,2H),8.20(dd,J=2.3,0.8Hz,1H),8.05(s,1H),7.95(t,J=6.1H z,1H),7.79(d,J=0.8Hz,1H),7.66(dd,J=7.7,2.3Hz,1H),7.53-7.46(m,2 H),7.33(d,J=7.9Hz,2H),6.97(d,J=1.3Hz,1H),4.53(s,2H),3.82(s,3H). The compound may also be referred to as [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-[6-(7-[1,2,4]triazol-1-yl-imidazo[1,2241 iridin-3-yl)-pyrimidin-4-yl]-amine.

[0522] 6-[7-(4-methyl-1H-imidazo1-yl)imidazo[1,2-a]pyridin-3-yl]-N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}pyrimidin-4-amine ("A267") [ka] From H1; White solid; MP 268-269°C; HPLC / MS [M+H] + 462. 1 H NMR(400MHz,DMSO-d6)δ9.89(d,J=7.7Hz,1H),8.57(s,1H),8.39(s,1H),8.-5-8.30(m,1H),8.08(s,1H),8.00(d,J=2.3Hz,1H),7.95(t ,J=6.2Hz,1H),7.82(s,1H),7.67(s,1H),7.-5-7.48(m,3H),7.35(d,J=7.9Hz,2H),6.97(s,1H),4.56(s,2H),3.85(s,3H),2.19(s,3H). The compound may also be referred to as {6-[7-(4-methyl-imidazol-1-yl)-imidazo[1,2242-pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine.

[0523] N-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-6-{7-[3-(methylamino)azetidin-1-yl]imidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine ("A268") [ka] From H1; White solid; MP 243-244°C; HPLC / MS [M+H] + 466. 1H NMR(400MHz,DMSO-d6)δ9.60(d,J=7.6Hz,1H),8.48(s,1H),8.07(s,1H),8.05-8 .02(m,1H),7.81(s,1H),7.77(t,J=6.1Hz,1H),7.51(d,J=7.9Hz,2H),7.34(d,J =7.8Hz,2H),6.82(s,1H),6.45(dd,J=7.6,2.3Hz,1H),6.30(d,J=2.4Hz,1H),4. 55-4.50(m,2H),4.13-4.04(m,2H),3.84(s,3H),3.64-3.56(m,3H),2.25(s,3H). The compound may also be referred to as {6-[7-(3-methylamino-azetidin-1-yl)-imidazo[1,2242-pyridin-3-yl]-pyrimidin-4-yl}-[4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-amine.

[0524] Example 32 "A75" salt: [4-(1-Methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine maleate 2-Propanol (2.5 ml) is added to [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine (25 mg, 49 μmol) and the suspension is heated to 50° C. Maleic acid (6.0 mg, 52 μmol) is added to the suspension and the mixture is stirred at 50° C. for 30 min. The mixture is slowly cooled to 5° C. Solid / liquid separation is carried out by centrifugation (5 min, 14000 rpm) and the resulting salt is dried at room temperature for 1 day to give [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine maleate as a white powder.

[0525] [4-(1-Methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine hydrochloride THF (2 ml) is added to [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine (25 mg, 49 μmol) and the suspension is heated to 50° C. An aqueous solution of hydrochloric acid (53 μl of a 1 M solution, 53 μmol) is added to the suspension and the mixture is stirred at 0° C. for 30 min. The mixture is slowly cooled to 5° C. Solid / liquid separation is performed by centrifugation (5 min, 14000 rpm) and the resulting salt is dried at room temperature for 1 day to give [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine hydrochloride as a white powder.

[0526] [4-(1-Methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine phosphate THF (2 ml) is added to [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine (25 mg, 49 μmol) and the suspension is heated to 50° C. An aqueous solution of phosphoric acid (37 μl of a 1.4 M solution, 53 μmol) is added to the suspension and the mixture is stirred at 50° C. for 30 min. The mixture is slowly cooled to 5° C. Solid / liquid separation is carried out by centrifugation (5 min, 14000 rpm) and the resulting salt is dried at room temperature for 1 day to give [4-(1-methyl-1H-pyrazol-4-yl)-benzyl]-{6-[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl}-amine phosphate as a white powder.

[0527] A75 Hydrochloride: IC50[M]c-Kit(V654A)=5.8E-09 IC50[M]GIST=2.1E-09.

[0528] The following examples relate to pharmaceuticals: Example A: Injection vial A solution of 100 g of the active ingredient of formula I and 5 g of disodium hydrogen phosphate in 3 L of double-distilled water is adjusted to pH 6.5 with 2 N hydrochloric acid, sterile filtered, transferred into injection vials, lyophilized under sterile conditions, and sealed under sterile conditions, each injection vial containing 5 mg of the active ingredient.

[0529] Example B: Suppositories A mixture of 20 g of an active ingredient of formula I with 100 g of soybean lecithin and 1400 g of cocoa butter is melted and poured into molds and allowed to cool. Each suppository contains 20 mg of the active ingredient.

[0530] Example C: Solution A solution is prepared from 1 g of the active ingredient of formula I, 9.38 g of NaH2PO4·2H2O, 28.48 g of Na2HPO4·12H2O, and 0.1 g of benzalkonium chloride in 940 ml of double-distilled water. The pH is adjusted to 6.8, the solution is made up to 1 L, and sterilized by irradiation. This solution can be used in the form of eye drops.

[0531] Example D: Ointment 500 mg of an active ingredient of formula I is mixed with 99.5 g of petrolatum under aseptic conditions.

[0532] Example E: Tablets A mixture of 1 kg of the active ingredient of formula I, 4 kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc, and 0.1 kg of magnesium stearate is compressed in a conventional manner to give tablets, each tablet containing 10 mg of the active ingredient.

[0533] Example F: Sugar-coated tablets Tablets are compressed similarly to Example E and then coated in a conventional manner with a coating of sucrose, potato starch, talc, tragacanth, and dye.

[0534] Example G: Capsule 2 kg of the active ingredient of formula I are conventionally introduced into hard gelatin capsules, each containing 20 mg of the active ingredient.

[0535] Example H: Ampoule A solution of 1 kg of the active ingredient of formula I in 60 L of double-distilled water is sterile-filtered into ampoules, lyophilized under sterile conditions and sealed under sterile conditions, each ampoule containing 10 mg of the active ingredient.

Claims

1. Compound [4-(1-methyl-1H-pyrazole-4-yl)-benzyl]-{6-[7-(3-pyrrolidine-1-yl-propoxy)-imidazo[1,2-a]pyridine-3-yl]pyrimidine-4-yl}amine or its tautomers and / or stereoisomers.

2. The compound according to Claim 1.

3. A pharmaceutical preparation in the form of a dosage unit comprising 0.5 mg to 1 g of [4-(1-methyl-1H-pyrazole-4-yl)-benzyl]-{6-[7-(3-pyrrolidine-1-yl-propoxy)-imidazo[1,2-a]pyridine-3-yl]pyrimidine-4-yl}amine or a pharmaceutically acceptable salt, tautomer, and / or stereoisomer.

4. The pharmaceutical formulation according to claim 3, wherein the dosage unit comprises 1 mg to 700 mg of [4-(1-methyl-1H-pyrazole-4-yl)-benzyl]-{6-[7-(3-pyrrolidine-1-yl-propoxy)-imidazo[1,2-a]pyridine-3-yl]-pyrimidine-4-yl}amine or a pharmaceutically acceptable salt, tautomer, and / or stereoisomer.

5. The pharmaceutical preparation according to claim 3, wherein the dosage unit comprises 5 mg to 100 mg of [4-(1-methyl-1H-pyrazole-4-yl)-benzyl]-{6-[7-(3-pyrrolidine-1-yl-propoxy)-imidazo[1,2-a]pyridine-3-yl]-pyrimidine-4-yl}amine or a pharmaceutically acceptable salt, tautomer, and / or stereoisomer.

6. The pharmaceutical formulation according to claim 3, wherein the form of the dosage unit comprises a daily dose or partial dose of [4-(1-methyl-1H-pyrazole-4-yl)-benzyl]-{6-[7-(3-pyrrolidine-1-yl-propoxy)-imidazo[1,2-a]pyridine-3-yl]-pyrimidine-4-yl}amine or a pharmaceutically acceptable salt thereof, tautomer, and / or stereoisomer.

7. A pharmaceutical formulation of [4-(1-methyl-1H-pyrazole-4-yl)-benzyl]-{6-[7-(3-pyrrolidine-1-yl-propoxy)-imidazo[1,2-a]pyridine-3-yl]-pyrimidine-4-yl}amine or a pharmaceutically acceptable salt, tautomer, and / or stereoisomer, wherein the formulation is suitable for oral administration.

8. The pharmaceutical preparation according to claim 7, wherein the preparation is in the form of a tablet or a capsule.

9. A process for producing the compound [4-(1-methyl-1H-pyrazole-4-yl)benzyl]-{6-[7-(3-pyrrolidine-1-ylpropoxy)imidazo[1,2-a]pyridine-3-yl]pyrimidine-4-yl}amine, characterized by reacting 6-[(E)-2-ethoxyethenyl]-N-{[4-(1-methyl-1H-pyrazole-4-yl)phenyl]methyl}pyrimidine-4-amine (G1) with 4-[3-(pyrrolidine-1-yl)propoxy]pyrimidine-2-amine (E15).

10. The process according to claim 9, wherein 6-[(E)-2-ethoxyethenyl]-N-{[4-(1-methyl-1H-pyrazole-4-yl)phenyl]methyl}pyrimidine-4-amine (G1) is reacted with 4-[3-(pyrrolidine-1-yl)propoxy]pyridine-2-amine (E15) in the presence of N-bromosuccinimide.