ZA200306540B - Process for the preparation of (3-cyano-1H-iondol-7-yl)[4-(4-fluorophenethyl)piperazin-1-yl]-methanone and salts thereof. - Google Patents
Process for the preparation of (3-cyano-1H-iondol-7-yl)[4-(4-fluorophenethyl)piperazin-1-yl]-methanone and salts thereof. Download PDFInfo
- Publication number
- ZA200306540B ZA200306540B ZA200306540A ZA200306540A ZA200306540B ZA 200306540 B ZA200306540 B ZA 200306540B ZA 200306540 A ZA200306540 A ZA 200306540A ZA 200306540 A ZA200306540 A ZA 200306540A ZA 200306540 B ZA200306540 B ZA 200306540B
- Authority
- ZA
- South Africa
- Prior art keywords
- formula
- indole
- salts
- cyano
- ethyl
- Prior art date
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- 150000003839 salts Chemical class 0.000 title claims description 41
- 238000000034 method Methods 0.000 title claims description 35
- 238000002360 preparation method Methods 0.000 title claims description 13
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 title 1
- -1 3-cyano-1H-indol-7-yl Chemical group 0.000 claims description 43
- 150000001875 compounds Chemical class 0.000 claims description 40
- FDASYGXNFLWEMM-UHFFFAOYSA-N 3-cyano-1h-indole-7-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1NC=C2C#N FDASYGXNFLWEMM-UHFFFAOYSA-N 0.000 claims description 20
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- LODHVDKKTUZVDK-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)ethyl]piperazine Chemical compound C1=CC(F)=CC=C1CCN1CCNCC1 LODHVDKKTUZVDK-UHFFFAOYSA-N 0.000 claims description 9
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 8
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 8
- 150000002923 oximes Chemical class 0.000 claims description 7
- 238000007098 aminolysis reaction Methods 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 230000026030 halogenation Effects 0.000 claims description 5
- 238000005658 halogenation reaction Methods 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
- 238000005580 one pot reaction Methods 0.000 claims description 3
- CBTITARLOCZPDU-UHFFFAOYSA-N 1h-indole-2-carbonitrile Chemical class C1=CC=C2NC(C#N)=CC2=C1 CBTITARLOCZPDU-UHFFFAOYSA-N 0.000 claims description 2
- 238000007333 cyanation reaction Methods 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 55
- 239000000203 mixture Substances 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 108090000371 Esterases Proteins 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- GYTQNBPGAFOSTP-UHFFFAOYSA-N ethyl 3-bromo-1h-indole-7-carboxylate Chemical compound CCOC(=O)C1=CC=CC2=C1NC=C2Br GYTQNBPGAFOSTP-UHFFFAOYSA-N 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- AQRLDDAFYYAIJP-UHFFFAOYSA-N Pruvanserin Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=3NC=C(C=3C=CC=2)C#N)CC1 AQRLDDAFYYAIJP-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- WQBIZOLLGSBVLW-UHFFFAOYSA-N ethyl 3-iodo-1h-indole-7-carboxylate Chemical compound CCOC(=O)C1=CC=CC2=C1NC=C2I WQBIZOLLGSBVLW-UHFFFAOYSA-N 0.000 description 4
- 230000022244 formylation Effects 0.000 description 4
- 238000006170 formylation reaction Methods 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- GXGCVEVNRZWNRA-UHFFFAOYSA-N methyl 3-cyano-1h-indole-7-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1NC=C2C#N GXGCVEVNRZWNRA-UHFFFAOYSA-N 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 238000007127 saponification reaction Methods 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- DGDAVTPQCQXLGU-UHFFFAOYSA-N 5437-38-7 Chemical compound CC1=CC=CC(C(O)=O)=C1[N+]([O-])=O DGDAVTPQCQXLGU-UHFFFAOYSA-N 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- WZXGOHXFXHUJLR-UHFFFAOYSA-N ethyl 1h-indole-7-carboxylate Chemical compound CCOC(=O)C1=CC=CC2=C1NC=C2 WZXGOHXFXHUJLR-UHFFFAOYSA-N 0.000 description 3
- 229940093499 ethyl acetate Drugs 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- FTLOEULOTNVCGF-UHFFFAOYSA-N methyl 1h-indole-7-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1NC=C2 FTLOEULOTNVCGF-UHFFFAOYSA-N 0.000 description 3
- JUXJMSUTGAQOBS-UHFFFAOYSA-N methyl 3-(hydroxyiminomethyl)-1H-indole-7-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1NC=C2C=NO JUXJMSUTGAQOBS-UHFFFAOYSA-N 0.000 description 3
- JVUPHJBFLSMOGY-UHFFFAOYSA-N methyl 3-formyl-1h-indole-7-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1NC=C2C=O JVUPHJBFLSMOGY-UHFFFAOYSA-N 0.000 description 3
- 235000011007 phosphoric acid Nutrition 0.000 description 3
- BWKAYBPLDRWMCJ-UHFFFAOYSA-N 1,1-diethoxy-n,n-dimethylmethanamine Chemical compound CCOC(N(C)C)OCC BWKAYBPLDRWMCJ-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- BJMPGMOWXAYATG-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)ethyl]piperazine;dihydrochloride Chemical compound Cl.Cl.C1=CC(F)=CC=C1CCN1CCNCC1 BJMPGMOWXAYATG-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 206010012335 Dependence Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- QPXSZQXPSYYDOP-UHFFFAOYSA-N benzyl 3-bromo-1h-indole-7-carboxylate Chemical compound C1=CC=C2C(Br)=CNC2=C1C(=O)OCC1=CC=CC=C1 QPXSZQXPSYYDOP-UHFFFAOYSA-N 0.000 description 2
- KUVRKVZNJFEROL-UHFFFAOYSA-N benzyl 3-iodo-1h-indole-7-carboxylate Chemical compound C1=CC=C2C(I)=CNC2=C1C(=O)OCC1=CC=CC=C1 KUVRKVZNJFEROL-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- NWSOTSIVONXYBH-UHFFFAOYSA-N ethyl 3-cyano-1h-indole-7-carboxylate Chemical compound CCOC(=O)C1=CC=CC2=C1NC=C2C#N NWSOTSIVONXYBH-UHFFFAOYSA-N 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- 229960004592 isopropanol Drugs 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- CGRCGYSAUITVAA-UHFFFAOYSA-N methyl 2-cyano-1h-indole-7-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1NC(C#N)=C2 CGRCGYSAUITVAA-UHFFFAOYSA-N 0.000 description 2
- XQYBKNRDFIWTDO-UHFFFAOYSA-N methyl 3-bromo-1h-indole-7-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1NC=C2Br XQYBKNRDFIWTDO-UHFFFAOYSA-N 0.000 description 2
- QHKCXKOTFXOTCP-UHFFFAOYSA-N methyl 3-iodo-1h-indole-7-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1NC=C2I QHKCXKOTFXOTCP-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
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- 229910052763 palladium Inorganic materials 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
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- 238000003756 stirring Methods 0.000 description 2
- KKVFSCTVCZYCMI-UHFFFAOYSA-N tert-butyl 3-bromo-1h-indole-7-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CC=CC2=C1NC=C2Br KKVFSCTVCZYCMI-UHFFFAOYSA-N 0.000 description 2
- RGURVNHQRAVPOX-UHFFFAOYSA-N tert-butyl 3-iodo-1h-indole-7-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CC=CC2=C1NC=C2I RGURVNHQRAVPOX-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
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- KEXFRBIOHPDZQM-UHFFFAOYSA-N 1,1-bis(2,2-dimethylpropoxy)-n,n-dimethylmethanamine Chemical compound CC(C)(C)COC(N(C)C)OCC(C)(C)C KEXFRBIOHPDZQM-UHFFFAOYSA-N 0.000 description 1
- GSFFXKGTGPMVLM-UHFFFAOYSA-N 1,1-dibutoxy-n,n-dimethylmethanamine Chemical compound CCCCOC(N(C)C)OCCCC GSFFXKGTGPMVLM-UHFFFAOYSA-N 0.000 description 1
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
- 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- SBNOTUDDIXOFSN-UHFFFAOYSA-N 1h-indole-2-carbaldehyde Chemical class C1=CC=C2NC(C=O)=CC2=C1 SBNOTUDDIXOFSN-UHFFFAOYSA-N 0.000 description 1
- OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
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- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- SHXWCVYOXRDMCX-UHFFFAOYSA-N 3,4-methylenedioxymethamphetamine Chemical compound CNC(C)CC1=CC=C2OCOC2=C1 SHXWCVYOXRDMCX-UHFFFAOYSA-N 0.000 description 1
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- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
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- 241000194110 Bacillus sp. (in: Bacteria) Species 0.000 description 1
- 238000005679 Batcho-Leimgruber synthesis reaction Methods 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108091007474 BsteE Proteins 0.000 description 1
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- JOSNOZILIPXEBS-LCYFTJDESA-N CCOC(=O)C1=CC=CC\2=C1NCC/2=N/O Chemical compound CCOC(=O)C1=CC=CC\2=C1NCC/2=N/O JOSNOZILIPXEBS-LCYFTJDESA-N 0.000 description 1
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Classifications
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- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D201/00—Preparation, separation, purification or stabilisation of unsubstituted lactams
- C07D201/02—Preparation of lactams
- C07D201/04—Preparation of lactams from or via oximes by Beckmann rearrangement
- C07D201/06—Preparation of lactams from or via oximes by Beckmann rearrangement from ketones by simultaneous oxime formation and rearrangement
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- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Addiction (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Toxicology (AREA)
- Vascular Medicine (AREA)
- Anesthesiology (AREA)
- Nutrition Science (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10102944A DE10102944A1 (de) | 2001-01-23 | 2001-01-23 | Verfahren zur Herstellung von (3-Cyan-1H-indol-7-yl)-[4-(4-fluorphenethyl)-piperazin-1-yl]-methanon und dessen Salzen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200306540B true ZA200306540B (en) | 2004-09-02 |
Family
ID=7671481
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200306540A ZA200306540B (en) | 2001-01-23 | 2003-08-21 | Process for the preparation of (3-cyano-1H-iondol-7-yl)[4-(4-fluorophenethyl)piperazin-1-yl]-methanone and salts thereof. |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US7312342B2 (sk) |
| EP (1) | EP1353906B1 (sk) |
| JP (1) | JP4215195B2 (sk) |
| KR (1) | KR100820763B1 (sk) |
| CN (1) | CN1213029C (sk) |
| AR (1) | AR032261A1 (sk) |
| AT (1) | ATE269849T1 (sk) |
| AU (1) | AU2002219220B2 (sk) |
| BR (1) | BR0116816A (sk) |
| CA (1) | CA2435426C (sk) |
| CZ (1) | CZ20032202A3 (sk) |
| DE (2) | DE10102944A1 (sk) |
| DK (1) | DK1353906T3 (sk) |
| EC (1) | ECSP034737A (sk) |
| ES (1) | ES2223738T3 (sk) |
| HK (1) | HK1063182A1 (sk) |
| HU (1) | HUP0401039A3 (sk) |
| IL (2) | IL157061A0 (sk) |
| MX (1) | MXPA03006534A (sk) |
| MY (1) | MY126252A (sk) |
| NZ (1) | NZ527779A (sk) |
| PL (1) | PL209416B1 (sk) |
| PT (1) | PT1353906E (sk) |
| RU (1) | RU2295519C2 (sk) |
| SK (1) | SK286565B6 (sk) |
| TR (1) | TR200402142T4 (sk) |
| TW (1) | TW588044B (sk) |
| UA (1) | UA74039C2 (sk) |
| WO (1) | WO2002059092A1 (sk) |
| ZA (1) | ZA200306540B (sk) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10246357A1 (de) * | 2002-10-04 | 2004-04-15 | Merck Patent Gmbh | Verwendung von 5-HT2Rezeptorantagonisten |
| DE102004047517A1 (de) * | 2004-09-28 | 2006-03-30 | Merck Patent Gmbh | Neuartige Kristallform von (3-Cyan-1H-indol-7-yl)-[4-(4-fluorphenethyl)-piperazin-1-yl]-methanon, Hydrochlorid |
| CN101437793B (zh) * | 2006-05-05 | 2012-08-22 | 默克专利股份有限公司 | 结晶的（3-氰基-1h-吲哚-7-基）-[4-（4-氟苯乙基）哌嗪-1-基]甲酮磷酸盐 |
| JP2009536208A (ja) | 2006-05-05 | 2009-10-08 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 結晶性（３−シアノ−１ｈ−インドール−７−イル）−［４−（４−フルオロフェネチル）ピペラジン−１−イル］メタノンホスフェート |
| CN102816104B (zh) * | 2012-08-30 | 2014-05-21 | 浙江大学 | 一种3-氰基吲哚类化合物的合成方法 |
-
2001
- 2001-01-23 DE DE10102944A patent/DE10102944A1/de not_active Withdrawn
- 2001-12-21 PL PL364392A patent/PL209416B1/pl not_active IP Right Cessation
- 2001-12-21 TR TR2004/02142T patent/TR200402142T4/xx unknown
- 2001-12-21 AT AT01273449T patent/ATE269849T1/de active
- 2001-12-21 PT PT01273449T patent/PT1353906E/pt unknown
- 2001-12-21 HU HU0401039A patent/HUP0401039A3/hu unknown
- 2001-12-21 ES ES01273449T patent/ES2223738T3/es not_active Expired - Lifetime
- 2001-12-21 US US10/466,991 patent/US7312342B2/en not_active Expired - Fee Related
- 2001-12-21 CZ CZ20032202A patent/CZ20032202A3/cs unknown
- 2001-12-21 UA UA2003076931A patent/UA74039C2/uk unknown
- 2001-12-21 SK SK1046-2003A patent/SK286565B6/sk not_active IP Right Cessation
- 2001-12-21 RU RU2003124068/04A patent/RU2295519C2/ru not_active IP Right Cessation
- 2001-12-21 IL IL15706101A patent/IL157061A0/xx unknown
- 2001-12-21 MX MXPA03006534A patent/MXPA03006534A/es active IP Right Grant
- 2001-12-21 DK DK01273449T patent/DK1353906T3/da active
- 2001-12-21 NZ NZ527779A patent/NZ527779A/xx unknown
- 2001-12-21 CA CA002435426A patent/CA2435426C/en not_active Expired - Fee Related
- 2001-12-21 WO PCT/EP2001/015240 patent/WO2002059092A1/en active IP Right Grant
- 2001-12-21 BR BR0116816-9A patent/BR0116816A/pt active Pending
- 2001-12-21 CN CNB018221882A patent/CN1213029C/zh not_active Expired - Fee Related
- 2001-12-21 AU AU2002219220A patent/AU2002219220B2/en not_active Ceased
- 2001-12-21 JP JP2002559394A patent/JP4215195B2/ja not_active Expired - Fee Related
- 2001-12-21 EP EP01273449A patent/EP1353906B1/en not_active Expired - Lifetime
- 2001-12-21 DE DE60104024T patent/DE60104024T2/de not_active Expired - Lifetime
- 2001-12-21 KR KR1020037009645A patent/KR100820763B1/ko not_active IP Right Cessation
-
2002
- 2002-01-17 TW TW091100688A patent/TW588044B/zh not_active IP Right Cessation
- 2002-01-18 MY MYPI20020201A patent/MY126252A/en unknown
- 2002-01-23 AR ARP020100222A patent/AR032261A1/es unknown
-
2003
- 2003-07-22 IL IL157061A patent/IL157061A/en not_active IP Right Cessation
- 2003-08-19 EC EC2003004737A patent/ECSP034737A/es unknown
- 2003-08-21 ZA ZA200306540A patent/ZA200306540B/en unknown
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2004
- 2004-08-09 HK HK04105893A patent/HK1063182A1/xx not_active IP Right Cessation
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