KR101614723B1 - Ｍｃｈ 길항물질로서 (1-아지논)-치환된 피리도인돌 - Google Patents

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Publication number

KR101614723B1

KR101614723B1 KR1020107017685A KR20107017685A KR101614723B1 KR 101614723 B1 KR101614723 B1 KR 101614723B1 KR 1020107017685 A KR1020107017685 A KR 1020107017685A KR 20107017685 A KR20107017685 A KR 20107017685A KR 101614723 B1 KR101614723 B1 KR 101614723B1

Authority

KR

South Korea

Prior art keywords

pyridin

mmol

pyrido

methyl

alkyl

Prior art date

2008-01-11

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.)

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• IVCGJOSPVGENCT-UHFFFAOYSA-N 1h-pyrrolo[2,3-f]quinoline Chemical class N1=CC=CC2=C(NC=C3)C3=CC=C21 IVCGJOSPVGENCT-UHFFFAOYSA-N 0.000 title abstract 2
• 239000005557 antagonist Substances 0.000 title description 2
• -1 substituted Chemical class 0.000 claims abstract description 391
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 66
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 38
• 125000003118 aryl group Chemical group 0.000 claims abstract description 34
• 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 32
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 18
• 125000005843 halogen group Chemical group 0.000 claims abstract description 17
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims abstract description 14
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 14
• 150000002367 halogens Chemical class 0.000 claims abstract description 14
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 8
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 6
• 239000011737 fluorine Substances 0.000 claims abstract description 5
• 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 3
• 150000001875 compounds Chemical class 0.000 claims description 473
• 238000000034 method Methods 0.000 claims description 311
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 82
• 150000003839 salts Chemical class 0.000 claims description 23
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
• 229910052757 nitrogen Inorganic materials 0.000 claims description 17
• 150000003840 hydrochlorides Chemical group 0.000 claims description 16
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 12
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 11
• 208000008589 Obesity Diseases 0.000 claims description 11
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
• 235000020824 obesity Nutrition 0.000 claims description 10
• 239000000126 substance Substances 0.000 claims description 10
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 125000001424 substituent group Chemical group 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 5
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• 208000019901 Anxiety disease Diseases 0.000 claims description 3
• 230000036506 anxiety Effects 0.000 claims description 3
• 229910052794 bromium Inorganic materials 0.000 claims description 3
• 125000005842 heteroatom Chemical group 0.000 claims description 3
• 229910052717 sulfur Inorganic materials 0.000 claims description 3
• 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 2
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
• 125000004442 acylamino group Chemical group 0.000 claims description 2
• 125000004414 alkyl thio group Chemical group 0.000 claims description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
• 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 2
• 125000001188 haloalkyl group Chemical group 0.000 claims description 2
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 2
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
• 150000003457 sulfones Chemical class 0.000 claims description 2
• 150000003462 sulfoxides Chemical class 0.000 claims description 2
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims 1
• 125000005518 carboxamido group Chemical group 0.000 claims 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
• 125000002950 monocyclic group Chemical group 0.000 claims 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 8
• 201000010099 disease Diseases 0.000 abstract description 6
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 480
• 239000007787 solid Substances 0.000 description 351
• 239000000243 solution Substances 0.000 description 343
• 239000000460 chlorine Substances 0.000 description 272
• 238000005481 NMR spectroscopy Methods 0.000 description 249
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 231
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 231
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 200
• 239000000203 mixture Substances 0.000 description 185
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 184
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 174
• 239000000725 suspension Substances 0.000 description 139
• 230000002829 reductive effect Effects 0.000 description 135
• 238000006243 chemical reaction Methods 0.000 description 129
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 126
• 238000003818 flash chromatography Methods 0.000 description 124
• 238000004128 high performance liquid chromatography Methods 0.000 description 124
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 121
• 239000000741 silica gel Substances 0.000 description 118
• 229910002027 silica gel Inorganic materials 0.000 description 118
• 239000011734 sodium Substances 0.000 description 111
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 94
• 235000019439 ethyl acetate Nutrition 0.000 description 94
• JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 74
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 72
• 239000011541 reaction mixture Substances 0.000 description 72
• 239000000843 powder Substances 0.000 description 67
• NRGKFNDKBDBBGY-UHFFFAOYSA-N 1h-pyridin-2-one;hydrochloride Chemical compound Cl.O=C1C=CC=CN1 NRGKFNDKBDBBGY-UHFFFAOYSA-N 0.000 description 61
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 61
• 229920006395 saturated elastomer Polymers 0.000 description 53
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 52
• GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 50
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 45
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
• 239000012074 organic phase Substances 0.000 description 45
• 238000000746 purification Methods 0.000 description 44
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 43
• 239000012267 brine Substances 0.000 description 38
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 38
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 36
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 34
• 239000012071 phase Substances 0.000 description 34
• 239000012458 free base Substances 0.000 description 32
• 125000006239 protecting group Chemical group 0.000 description 32
• 238000009472 formulation Methods 0.000 description 31
• 239000002904 solvent Substances 0.000 description 31
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
• 238000001914 filtration Methods 0.000 description 28
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• 239000003921 oil Substances 0.000 description 27
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
• 238000003756 stirring Methods 0.000 description 26
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 25
• 235000019198 oils Nutrition 0.000 description 25
• 239000005725 8-Hydroxyquinoline Substances 0.000 description 24
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
• 229960003540 oxyquinoline Drugs 0.000 description 24
• MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 24
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
• 239000000706 filtrate Substances 0.000 description 23
• 239000003795 chemical substances by application Substances 0.000 description 22
• 239000006260 foam Substances 0.000 description 22
• 238000010511 deprotection reaction Methods 0.000 description 21
• IDCBQVLMQMNDSJ-UHFFFAOYSA-N tert-butyl 7-bromo-5-methyl-3,4-dihydro-1h-pyrido[4,3-b]indole-2-carboxylate Chemical compound C12=CC=C(Br)C=C2N(C)C2=C1CN(C(=O)OC(C)(C)C)CC2 IDCBQVLMQMNDSJ-UHFFFAOYSA-N 0.000 description 21
• 238000010992 reflux Methods 0.000 description 20
• 229910000104 sodium hydride Inorganic materials 0.000 description 19
• YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
• 229910052786 argon Inorganic materials 0.000 description 18
• 238000002360 preparation method Methods 0.000 description 18
• 229910021529 ammonia Inorganic materials 0.000 description 17
• 239000008346 aqueous phase Substances 0.000 description 17
• 239000006185 dispersion Substances 0.000 description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
• 239000000284 extract Substances 0.000 description 16
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 16
• DOVNUEPFPBWTSV-UHFFFAOYSA-N 4-phenylmethoxy-1h-pyridin-2-one Chemical compound C1=CNC(=O)C=C1OCC1=CC=CC=C1 DOVNUEPFPBWTSV-UHFFFAOYSA-N 0.000 description 15
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
• 239000002585 base Substances 0.000 description 15
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 15
• 238000001816 cooling Methods 0.000 description 15
• 239000002480 mineral oil Substances 0.000 description 15
• 235000010446 mineral oil Nutrition 0.000 description 15
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 15
• JRSSLWBCCBXOCK-UHFFFAOYSA-N tert-butyl 7-bromo-9-methyl-3,4-dihydro-1h-pyrido[3,4-b]indole-2-carboxylate Chemical compound C12=CC=C(Br)C=C2N(C)C2=C1CCN(C(=O)OC(C)(C)C)C2 JRSSLWBCCBXOCK-UHFFFAOYSA-N 0.000 description 15
• NRESDXFFSNBDGP-UHFFFAOYSA-N (4-bromophenyl)hydrazine Chemical compound NNC1=CC=C(Br)C=C1 NRESDXFFSNBDGP-UHFFFAOYSA-N 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 13
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 13
• XIUFMOWIWSJHNC-UHFFFAOYSA-N 5h-indole-2-carboxylic acid Chemical compound C1C=CC2=NC(C(=O)O)=CC2=C1 XIUFMOWIWSJHNC-UHFFFAOYSA-N 0.000 description 13
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• 239000012044 organic layer Substances 0.000 description 12
• 238000002953 preparative HPLC Methods 0.000 description 12
• 239000003054 catalyst Substances 0.000 description 11
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 11
• 239000007788 liquid Substances 0.000 description 11
• DPJVRASYWYOFSJ-UHFFFAOYSA-N 4-chloro-1-oxidopyridin-1-ium Chemical compound [O-][N+]1=CC=C(Cl)C=C1 DPJVRASYWYOFSJ-UHFFFAOYSA-N 0.000 description 10
• 125000002252 acyl group Chemical group 0.000 description 10
• 230000008569 process Effects 0.000 description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
• 239000000443 aerosol Substances 0.000 description 9
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 9
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 8
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
• 150000007942 carboxylates Chemical class 0.000 description 8
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 239000012312 sodium hydride Substances 0.000 description 8
• LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical group OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 7
• WJRKNLONLOMALV-UHFFFAOYSA-N 5-chloropyridine Chemical compound ClC1=C=NC=C[CH]1 WJRKNLONLOMALV-UHFFFAOYSA-N 0.000 description 7
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
• 101150003085 Pdcl gene Proteins 0.000 description 7
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 239000000908 ammonium hydroxide Substances 0.000 description 7
• 239000003814 drug Substances 0.000 description 7
• 239000001257 hydrogen Substances 0.000 description 7
• 239000004615 ingredient Substances 0.000 description 7
• 239000002245 particle Substances 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 6
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• 239000012298 atmosphere Substances 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000007872 degassing Methods 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 238000001035 drying Methods 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 6
• 230000029936 alkylation Effects 0.000 description 5
• 239000001301 oxygen Substances 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• MFCWFKQMLTWWCD-UHFFFAOYSA-N 1-(5-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-7-yl)-4-phenylmethoxypyridin-2-one Chemical compound C1=C2N(C)C=3CCNCC=3C2=CC=C1N(C(C=1)=O)C=CC=1OCC1=CC=CC=C1 MFCWFKQMLTWWCD-UHFFFAOYSA-N 0.000 description 4
• MXDRPNGTQDRKQM-UHFFFAOYSA-N 3-methylpyridazine Chemical compound CC1=CC=CN=N1 MXDRPNGTQDRKQM-UHFFFAOYSA-N 0.000 description 4
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