JP5608097B2 - キナーゼ阻害薬としてのピロロピリジン - Google Patents

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Publication number

JP5608097B2

JP5608097B2 JP2010542341A JP2010542341A JP5608097B2 JP 5608097 B2 JP5608097 B2 JP 5608097B2 JP 2010542341 A JP2010542341 A JP 2010542341A JP 2010542341 A JP2010542341 A JP 2010542341A JP 5608097 B2 JP5608097 B2 JP 5608097B2

Authority

JP

Japan

Prior art keywords

mmol

pyrrolo

reaction

phenyl

dcm

Prior art date

2008-01-08

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

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• XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 title 1
• 229940043355 kinase inhibitor Drugs 0.000 title 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 252
• -1 1-oxa-3,4-diazolyl Chemical group 0.000 claims description 115
• 229910052739 hydrogen Inorganic materials 0.000 claims description 98
• 239000001257 hydrogen Substances 0.000 claims description 93
• 229910052736 halogen Inorganic materials 0.000 claims description 89
• 150000002367 halogens Chemical class 0.000 claims description 88
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 88
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 74
• 150000003839 salts Chemical class 0.000 claims description 68
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 49
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 32
• 125000000217 alkyl group Chemical group 0.000 claims description 32
• 125000000623 heterocyclic group Chemical group 0.000 claims description 32
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 32
• 239000011570 nicotinamide Substances 0.000 claims description 27
• 229960003966 nicotinamide Drugs 0.000 claims description 27
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
• 235000005152 nicotinamide Nutrition 0.000 claims description 25
• 125000001072 heteroaryl group Chemical group 0.000 claims description 24
• 229910052757 nitrogen Inorganic materials 0.000 claims description 23
• 150000002431 hydrogen Chemical class 0.000 claims description 19
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 13
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 11
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
• 125000004429 atom Chemical group 0.000 claims description 10
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 8
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
• 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 7
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 7
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 7
• 125000004076 pyridyl group Chemical group 0.000 claims description 7
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 5
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 4
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• 125000001544 thienyl group Chemical group 0.000 claims description 4
• ZVXKYWHJBYIYNI-UHFFFAOYSA-N 1h-pyrazole-4-carboxamide Chemical compound NC(=O)C=1C=NNC=1 ZVXKYWHJBYIYNI-UHFFFAOYSA-N 0.000 claims description 3
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• BCCUXBGEPLKSEX-UHFFFAOYSA-N 5-methylpyridine-3-carboxamide Chemical compound CC1=CN=CC(C(N)=O)=C1 BCCUXBGEPLKSEX-UHFFFAOYSA-N 0.000 claims description 3
• CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 2
• DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims description 2
• 125000005843 halogen group Chemical group 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 577
• 238000006243 chemical reaction Methods 0.000 description 323
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 216
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 182
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 148
• 239000000243 solution Substances 0.000 description 143
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 112
• 239000007787 solid Substances 0.000 description 85
• 239000000203 mixture Substances 0.000 description 84
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 81
• 238000000034 method Methods 0.000 description 80
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 68
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 64
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
• 239000011734 sodium Substances 0.000 description 60
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 58
• 229920006395 saturated elastomer Polymers 0.000 description 56
• 235000019439 ethyl acetate Nutrition 0.000 description 55
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 53
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 52
• 238000011282 treatment Methods 0.000 description 51
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 47
• 238000004440 column chromatography Methods 0.000 description 43
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 42
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 40
• 201000010099 disease Diseases 0.000 description 38
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 35
• 206010028980 Neoplasm Diseases 0.000 description 33
• 239000012043 crude product Substances 0.000 description 33
• 239000003921 oil Substances 0.000 description 32
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 29
• 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 description 28
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 27
• 241000124008 Mammalia Species 0.000 description 27
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
• 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 description 27
• 238000004587 chromatography analysis Methods 0.000 description 26
• 230000003463 hyperproliferative effect Effects 0.000 description 26
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 25
• 201000011510 cancer Diseases 0.000 description 25
• 239000002253 acid Substances 0.000 description 23
• GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 23
• 239000000047 product Substances 0.000 description 22
• 239000012265 solid product Substances 0.000 description 22
• 239000003112 inhibitor Substances 0.000 description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
• 238000001514 detection method Methods 0.000 description 20
• 238000000746 purification Methods 0.000 description 20
• 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 description 19
• 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 description 19
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• 210000004027 cell Anatomy 0.000 description 18
• 125000006239 protecting group Chemical group 0.000 description 18
• 208000024891 symptom Diseases 0.000 description 18
• 239000010410 layer Substances 0.000 description 17
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
• 150000001413 amino acids Chemical class 0.000 description 16
• 125000003118 aryl group Chemical group 0.000 description 16
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
• 208000035475 disorder Diseases 0.000 description 15
• 239000012267 brine Substances 0.000 description 14
• 239000003153 chemical reaction reagent Substances 0.000 description 14
• 150000002148 esters Chemical class 0.000 description 14
• 238000004519 manufacturing process Methods 0.000 description 14
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
• 239000002904 solvent Substances 0.000 description 14
• GQWRBNJRKSPGTF-CQSZACIVSA-N (2s)-2-(4-chlorophenyl)-3-[(2-methylpropan-2-yl)oxycarbonyl-propan-2-ylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N(C(C)C)C[C@@H](C(O)=O)C1=CC=C(Cl)C=C1 GQWRBNJRKSPGTF-CQSZACIVSA-N 0.000 description 13
• 238000005481 NMR spectroscopy Methods 0.000 description 13
• 229910052799 carbon Inorganic materials 0.000 description 13
• 239000003814 drug Substances 0.000 description 13
• 238000001914 filtration Methods 0.000 description 13
• 239000008194 pharmaceutical composition Substances 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• 238000003786 synthesis reaction Methods 0.000 description 13
• 238000005859 coupling reaction Methods 0.000 description 12
• 239000012044 organic layer Substances 0.000 description 12
• 230000015572 biosynthetic process Effects 0.000 description 11
• 238000010168 coupling process Methods 0.000 description 11
• 239000000543 intermediate Substances 0.000 description 11
• 238000000926 separation method Methods 0.000 description 11
• OVPLZYJGTGDFNB-UHFFFAOYSA-N propan-2-yl carbamate Chemical compound CC(C)OC(N)=O OVPLZYJGTGDFNB-UHFFFAOYSA-N 0.000 description 10
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 10
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
• 208000009956 adenocarcinoma Diseases 0.000 description 9
• 150000001412 amines Chemical class 0.000 description 9
• 230000008878 coupling Effects 0.000 description 9
• 125000000753 cycloalkyl group Chemical group 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
• MBYQIHCBCCZXDZ-UHFFFAOYSA-N 3-methyl-5-phenyl-4-piperazin-1-yl-1h-pyrrolo[2,3-b]pyridine Chemical compound C1CNCCN1C1=C2C(C)=CNC2=NC=C1C1=CC=CC=C1 MBYQIHCBCCZXDZ-UHFFFAOYSA-N 0.000 description 8
• 0 CC(*)(CN(CC1)C(C(*)*N(*)*)=O)CN1c1c(*)cnc2c1c(*)c[n]2 Chemical compound CC(*)(CN(CC1)C(C(*)*N(*)*)=O)CN1c1c(*)cnc2c1c(*)c[n]2 0.000 description 8
• 201000009030 Carcinoma Diseases 0.000 description 8
• 206010025323 Lymphomas Diseases 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• 230000002159 abnormal effect Effects 0.000 description 8
• 239000002246 antineoplastic agent Substances 0.000 description 8
• 238000001212 derivatisation Methods 0.000 description 8
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
• 238000002360 preparation method Methods 0.000 description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• 125000001424 substituent group Chemical group 0.000 description 8
• 206010039491 Sarcoma Diseases 0.000 description 7
• 229910004298 SiO 2 Inorganic materials 0.000 description 7
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
• 125000006242 amine protecting group Chemical group 0.000 description 7
• 239000010779 crude oil Substances 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 229910052938 sodium sulfate Inorganic materials 0.000 description 7
• 235000011152 sodium sulphate Nutrition 0.000 description 7
• 206010041823 squamous cell carcinoma Diseases 0.000 description 7
• 238000004809 thin layer chromatography Methods 0.000 description 7
• IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 6
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
• UBBFOEJAGGJZDA-UHFFFAOYSA-N 5-phenyl-4-piperazin-1-yl-1h-pyrrolo[2,3-b]pyridine;dihydrochloride Chemical compound Cl.Cl.C1CNCCN1C1=C(C=2C=CC=CC=2)C=NC2=C1C=CN2 UBBFOEJAGGJZDA-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
• 108091000080 Phosphotransferase Proteins 0.000 description 6
• 150000001336 alkenes Chemical class 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 238000005984 hydrogenation reaction Methods 0.000 description 6
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 6
• 239000000546 pharmaceutical excipient Substances 0.000 description 6
• 102000020233 phosphotransferase Human genes 0.000 description 6
• 150000003141 primary amines Chemical class 0.000 description 6
• BETBOAZCLSJOBQ-LLVKDONJSA-N (2r)-3-(4-chlorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)CC1=CC=C(Cl)C=C1 BETBOAZCLSJOBQ-LLVKDONJSA-N 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 5
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
• 239000002841 Lewis acid Substances 0.000 description 5
• 230000010261 cell growth Effects 0.000 description 5
• 229940126214 compound 3 Drugs 0.000 description 5
• 150000007517 lewis acids Chemical class 0.000 description 5
• MMGDUOFJZARVSP-UHFFFAOYSA-N n-(4-piperazin-1-yl-1h-pyrrolo[2,3-b]pyridin-3-yl)pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NC(C=12)=CNC2=NC=CC=1N1CCNCC1 MMGDUOFJZARVSP-UHFFFAOYSA-N 0.000 description 5
• RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 5
• 230000005855 radiation Effects 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• XDIQYLQINKZOHN-JOCHJYFZSA-N tert-butyl n-[(2s)-3-[4-(5-bromo-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl]-2-(4-chlorophenyl)-3-oxopropyl]-n-propan-2-ylcarbamate Chemical compound C1([C@H](C(=O)N2CCN(CC2)C=2C=3C=CNC=3N=CC=2Br)CN(C(C)C)C(=O)OC(C)(C)C)=CC=C(Cl)C=C1 XDIQYLQINKZOHN-JOCHJYFZSA-N 0.000 description 5
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
• XNWFHHBKLYJQMS-UHFFFAOYSA-N 1-(benzenesulfonyl)-5-bromo-4-chloropyrrolo[2,3-b]pyridine Chemical compound C1=CC=2C(Cl)=C(Br)C=NC=2N1S(=O)(=O)C1=CC=CC=C1 XNWFHHBKLYJQMS-UHFFFAOYSA-N 0.000 description 4
• WCFJUSRQHZPVKY-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NCCC(O)=O WCFJUSRQHZPVKY-UHFFFAOYSA-N 0.000 description 4
• HIVCRVALIJNGRU-UHFFFAOYSA-N 4-(4-benzylpiperazin-1-yl)-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C=12C(N)=CNC2=NC=CC=1N(CC1)CCN1CC1=CC=CC=C1 HIVCRVALIJNGRU-UHFFFAOYSA-N 0.000 description 4
• UNWHCJJKUQVNGX-UHFFFAOYSA-N 5-(3-fluorophenyl)-4-piperazin-1-yl-1h-pyrrolo[2,3-b]pyridine Chemical compound FC1=CC=CC(C=2C(=C3C=CNC3=NC=2)N2CCNCC2)=C1 UNWHCJJKUQVNGX-UHFFFAOYSA-N 0.000 description 4
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
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