UA74039C2 - A process for the preparation of (3-cyano-1h-indol-7-yl)[4-(4-fluorophenethyl)piperazin-1-yl]-methanone and salts thereof - Google Patents
A process for the preparation of (3-cyano-1h-indol-7-yl)[4-(4-fluorophenethyl)piperazin-1-yl]-methanone and salts thereof Download PDFInfo
- Publication number
- UA74039C2 UA74039C2 UA2003076931A UA2003076931A UA74039C2 UA 74039 C2 UA74039 C2 UA 74039C2 UA 2003076931 A UA2003076931 A UA 2003076931A UA 2003076931 A UA2003076931 A UA 2003076931A UA 74039 C2 UA74039 C2 UA 74039C2
- Authority
- UA
- Ukraine
- Prior art keywords
- formula
- indole
- salts
- cyano
- acid
- Prior art date
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- 150000003839 salts Chemical class 0.000 title claims abstract description 42
- 238000000034 method Methods 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title abstract description 5
- 230000008569 process Effects 0.000 title abstract 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 title abstract 2
- -1 indole ester Chemical class 0.000 claims abstract description 49
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims abstract description 11
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims abstract description 9
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims abstract description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 44
- 150000001875 compounds Chemical class 0.000 claims description 38
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-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
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 150000002148 esters Chemical class 0.000 claims description 14
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims description 10
- 239000003513 alkali Substances 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 230000003993 interaction Effects 0.000 claims description 7
- 150000002923 oximes Chemical class 0.000 claims description 7
- 238000007127 saponification reaction Methods 0.000 claims description 7
- 238000007098 aminolysis reaction Methods 0.000 claims description 6
- 230000026030 halogenation Effects 0.000 claims description 6
- 238000005658 halogenation reaction Methods 0.000 claims description 6
- 238000010306 acid treatment Methods 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
- 230000022244 formylation Effects 0.000 claims description 3
- 238000006170 formylation reaction Methods 0.000 claims description 3
- CBTITARLOCZPDU-UHFFFAOYSA-N 1h-indole-2-carbonitrile Chemical compound C1=CC=C2NC(C#N)=CC2=C1 CBTITARLOCZPDU-UHFFFAOYSA-N 0.000 claims description 2
- 238000007333 cyanation reaction Methods 0.000 claims description 2
- 238000012876 topography Methods 0.000 claims 1
- 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 abstract description 7
- LODHVDKKTUZVDK-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)ethyl]piperazine Chemical compound C1=CC(F)=CC=C1CCN1CCNCC1 LODHVDKKTUZVDK-UHFFFAOYSA-N 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
- 239000000203 mixture Substances 0.000 description 23
- 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
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 14
- 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
- 239000002253 acid Substances 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- IPDOBVFESNNYEE-UHFFFAOYSA-N 1h-indole-7-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1NC=C2 IPDOBVFESNNYEE-UHFFFAOYSA-N 0.000 description 9
- JEWXETWMNLOZDO-UHFFFAOYSA-N 3-bromo-1h-indole-7-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1NC=C2Br JEWXETWMNLOZDO-UHFFFAOYSA-N 0.000 description 9
- XPFPSGUINDMCAV-UHFFFAOYSA-N 3-iodo-1h-indole-7-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1NC=C2I XPFPSGUINDMCAV-UHFFFAOYSA-N 0.000 description 9
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- 238000003786 synthesis reaction Methods 0.000 description 8
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- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-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
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- 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
- 150000007513 acids Chemical class 0.000 description 6
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 239000000543 intermediate Chemical class 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
- WIHFHPBFUKDVDX-UHFFFAOYSA-N ON=C1CNC2=C(C=CC=C12)C(=O)O Chemical compound ON=C1CNC2=C(C=CC=C12)C(=O)O WIHFHPBFUKDVDX-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
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000003814 drug Substances 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
- 150000004702 methyl esters Chemical class 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
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- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
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- 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
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
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- 239000011541 reaction mixture Substances 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- CHIFTAQVXHNVRW-UHFFFAOYSA-N 1h-indole-3-carbonitrile Chemical compound C1=CC=C2C(C#N)=CNC2=C1 CHIFTAQVXHNVRW-UHFFFAOYSA-N 0.000 description 2
- SHXWCVYOXRDMCX-UHFFFAOYSA-N 3,4-methylenedioxymethamphetamine Chemical compound CNC(C)CC1=CC=C2OCOC2=C1 SHXWCVYOXRDMCX-UHFFFAOYSA-N 0.000 description 2
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- 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
-
- 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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Toxicology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Addiction (AREA)
- Nutrition Science (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| 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 |
| PCT/EP2001/015240 WO2002059092A1 (en) | 2001-01-23 | 2001-12-21 | Process for the preparation of (3-cyano-1h-indol-7-yl)(4-(4-fluorophenethyl)piperazin-1-yl)-methanone and salts thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA74039C2 true UA74039C2 (en) | 2005-10-17 |
Family
ID=7671481
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2003076931A UA74039C2 (en) | 2001-01-23 | 2001-12-21 | A process for the preparation of (3-cyano-1h-indol-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 |
| ES2388000T3 (es) * | 2006-05-05 | 2012-10-05 | Merck Patent Gmbh | Fosfato de (3-ciano-1H-indol-7-il)-[4-(4-fluorofenetil)piperazin-1-il]metanona cristalino |
| 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 IL IL15706101A patent/IL157061A0/xx unknown
- 2001-12-21 DE DE60104024T patent/DE60104024T2/de not_active Expired - Lifetime
- 2001-12-21 HU HU0401039A patent/HUP0401039A3/hu unknown
- 2001-12-21 RU RU2003124068/04A patent/RU2295519C2/ru not_active IP Right Cessation
- 2001-12-21 BR BR0116816-9A patent/BR0116816A/pt active Pending
- 2001-12-21 KR KR1020037009645A patent/KR100820763B1/ko not_active IP Right Cessation
- 2001-12-21 AU AU2002219220A patent/AU2002219220B2/en not_active Ceased
- 2001-12-21 MX MXPA03006534A patent/MXPA03006534A/es active IP Right Grant
- 2001-12-21 CA CA002435426A patent/CA2435426C/en not_active Expired - Fee Related
- 2001-12-21 CZ CZ20032202A patent/CZ20032202A3/cs unknown
- 2001-12-21 JP JP2002559394A patent/JP4215195B2/ja not_active Expired - Fee Related
- 2001-12-21 DK DK01273449T patent/DK1353906T3/da active
- 2001-12-21 NZ NZ527779A patent/NZ527779A/xx unknown
- 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 EP EP01273449A patent/EP1353906B1/en not_active Expired - Lifetime
- 2001-12-21 WO PCT/EP2001/015240 patent/WO2002059092A1/en active IP Right Grant
- 2001-12-21 UA UA2003076931A patent/UA74039C2/uk unknown
- 2001-12-21 CN CNB018221882A patent/CN1213029C/zh not_active Expired - Fee Related
- 2001-12-21 PT PT01273449T patent/PT1353906E/pt unknown
- 2001-12-21 AT AT01273449T patent/ATE269849T1/de active
- 2001-12-21 SK SK1046-2003A patent/SK286565B6/sk not_active IP Right Cessation
- 2001-12-21 US US10/466,991 patent/US7312342B2/en not_active Expired - Fee Related
- 2001-12-21 ES ES01273449T patent/ES2223738T3/es not_active Expired - Lifetime
-
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
-
2004
- 2004-08-09 HK HK04105893A patent/HK1063182A1/xx not_active IP Right Cessation
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