SK286425B6 - Spôsob výroby R-(+)-6-karboxamido-3-N-metylamino-1,2,3,4- tetrahydrokarbazolu a použitie kyseliny L-pyroglutámovej - Google Patents
Spôsob výroby R-(+)-6-karboxamido-3-N-metylamino-1,2,3,4- tetrahydrokarbazolu a použitie kyseliny L-pyroglutámovej Download PDFInfo
- Publication number
- SK286425B6 SK286425B6 SK1518-2000A SK15182000A SK286425B6 SK 286425 B6 SK286425 B6 SK 286425B6 SK 15182000 A SK15182000 A SK 15182000A SK 286425 B6 SK286425 B6 SK 286425B6
- Authority
- SK
- Slovakia
- Prior art keywords
- tetrahydrocarbazole
- methylamino
- mixture
- carboxamido
- salt
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 29
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 53
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 12
- 239000012453 solvate Substances 0.000 claims abstract description 11
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 17
- CBTITARLOCZPDU-UHFFFAOYSA-N 1h-indole-2-carbonitrile Chemical compound C1=CC=C2NC(C#N)=CC2=C1 CBTITARLOCZPDU-UHFFFAOYSA-N 0.000 claims description 15
- 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 claims description 9
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 8
- KJIMZXWXSLVBEO-UHFFFAOYSA-N 4-(methylamino)cyclohexan-1-one Chemical compound CNC1CCC(=O)CC1 KJIMZXWXSLVBEO-UHFFFAOYSA-N 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- DCZFGQYXRKMVFG-UHFFFAOYSA-N cyclohexane-1,4-dione Chemical compound O=C1CCC(=O)CC1 DCZFGQYXRKMVFG-UHFFFAOYSA-N 0.000 claims description 2
- DZUUSHCOMPROCJ-UHFFFAOYSA-N 4-hydrazinylbenzonitrile Chemical compound NNC1=CC=C(C#N)C=C1 DZUUSHCOMPROCJ-UHFFFAOYSA-N 0.000 claims 2
- ORRBHGDXBDFSFM-UHFFFAOYSA-N 1h-indole;nitric acid Chemical compound O[N+]([O-])=O.C1=CC=C2NC=CC2=C1 ORRBHGDXBDFSFM-UHFFFAOYSA-N 0.000 claims 1
- COKVDTKAWIFNTH-UHFFFAOYSA-N 3,3-dimethyl-1,5-dioxaspiro[5.5]undecan-9-one Chemical compound O1CC(C)(C)COC11CCC(=O)CC1 COKVDTKAWIFNTH-UHFFFAOYSA-N 0.000 claims 1
- XQYQABVPFWOITO-UHFFFAOYSA-N CCC(CC(C)=O)NC Chemical compound CCC(CC(C)=O)NC XQYQABVPFWOITO-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- 239000000243 solution Substances 0.000 description 46
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 33
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 25
- 239000007787 solid Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 16
- 238000010992 reflux Methods 0.000 description 13
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 12
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 11
- 238000005406 washing Methods 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- 239000012258 stirred mixture Substances 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- XKLNOVWDVMWTOB-UHFFFAOYSA-N 2,3,4,9-tetrahydro-1h-carbazole Chemical class N1C2=CC=CC=C2C2=C1CCCC2 XKLNOVWDVMWTOB-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000002329 infrared spectrum Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000001384 succinic acid Substances 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 150000004682 monohydrates Chemical class 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- ZNWLFTSPNBLXGL-UHFFFAOYSA-N 4-(1,4-dioxaspiro[4.5]decan-8-yl)cyclohexan-1-one Chemical compound C1CC(=O)CCC1C1CCC2(OCCO2)CC1 ZNWLFTSPNBLXGL-UHFFFAOYSA-N 0.000 description 3
- ODHCTXKNWHHXJC-GSVOUGTGSA-N 5-oxo-D-proline Chemical compound OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 3
- 229910015900 BF3 Inorganic materials 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000008034 disappearance Effects 0.000 description 3
- -1 indolenitrile compound Chemical class 0.000 description 3
- 229940043131 pyroglutamate Drugs 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- QDFBQPPJRJWGFO-UHFFFAOYSA-N 1h-indole-2-carbonitrile;hydrochloride Chemical compound Cl.C1=CC=C2NC(C#N)=CC2=C1 QDFBQPPJRJWGFO-UHFFFAOYSA-N 0.000 description 2
- UXDLLFIRCVPPQP-UHFFFAOYSA-N 4-hydrazinylbenzonitrile;hydrochloride Chemical compound [Cl-].[NH3+]NC1=CC=C(C#N)C=C1 UXDLLFIRCVPPQP-UHFFFAOYSA-N 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- OWIOWWPDSOTTNG-UHFFFAOYSA-N 6-amino-6,7,8,9-tetrahydro-5h-carbazole-3-carboxamide;hydrochloride Chemical compound Cl.N1C2=CC=C(C(N)=O)C=C2C2=C1CCC(N)C2 OWIOWWPDSOTTNG-UHFFFAOYSA-N 0.000 description 1
- XCINZDTUNROCPR-UHFFFAOYSA-N C12=CC=CC=C2N(NC)C2=C1CCCC2 Chemical compound C12=CC=CC=C2N(NC)C2=C1CCCC2 XCINZDTUNROCPR-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000000609 carbazolyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000010956 selective crystallization Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
-
- 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9808069.0A GB9808069D0 (en) | 1998-04-16 | 1998-04-16 | Novel processes |
| PCT/GB1999/001167 WO1999054302A1 (en) | 1998-04-16 | 1999-04-16 | Process for the production of r-(+)-6- carboxamido- 3-n- methylamino- 1,2,3,4- tetrahydrocarbazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK15182000A3 SK15182000A3 (sk) | 2001-06-11 |
| SK286425B6 true SK286425B6 (sk) | 2008-09-05 |
Family
ID=10830430
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1518-2000A SK286425B6 (sk) | 1998-04-16 | 1999-04-16 | Spôsob výroby R-(+)-6-karboxamido-3-N-metylamino-1,2,3,4- tetrahydrokarbazolu a použitie kyseliny L-pyroglutámovej |
Country Status (33)
| Country | Link |
|---|---|
| US (1) | US6359146B1 (tr) |
| EP (1) | EP1070051B1 (tr) |
| JP (1) | JP4756740B2 (tr) |
| KR (1) | KR100612183B1 (tr) |
| CN (1) | CN1200931C (tr) |
| AR (1) | AR015771A1 (tr) |
| AU (1) | AU3437099A (tr) |
| BR (1) | BR9909627A (tr) |
| CA (1) | CA2328345C (tr) |
| CY (1) | CY1116418T1 (tr) |
| CZ (1) | CZ297303B6 (tr) |
| DK (1) | DK1070051T3 (tr) |
| EA (1) | EA004586B1 (tr) |
| EE (1) | EE05156B1 (tr) |
| ES (1) | ES2541432T3 (tr) |
| GB (1) | GB9808069D0 (tr) |
| HR (1) | HRP20000683B1 (tr) |
| HU (1) | HU230559B1 (tr) |
| ID (1) | ID26783A (tr) |
| IL (1) | IL139017A (tr) |
| MX (1) | MXPA00010127A (tr) |
| MY (1) | MY126530A (tr) |
| NO (1) | NO317883B1 (tr) |
| PL (1) | PL210864B1 (tr) |
| PT (1) | PT1070051E (tr) |
| SI (1) | SI1070051T1 (tr) |
| SK (1) | SK286425B6 (tr) |
| TR (1) | TR200100142T2 (tr) |
| TW (1) | TWI255812B (tr) |
| UA (1) | UA70943C2 (tr) |
| WO (1) | WO1999054302A1 (tr) |
| YU (1) | YU62800A (tr) |
| ZA (1) | ZA200006303B (tr) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010073253A1 (en) * | 2008-12-22 | 2010-07-01 | Natco Pharma Limited | Method for preparing an optically active frovatriptan |
| WO2011095803A1 (en) * | 2010-02-02 | 2011-08-11 | Generics [Uk] Limited | Hplc method for analyzing frovatriptan |
| EP2816030A1 (en) | 2013-06-20 | 2014-12-24 | Duke Chem, S. A. | Process for the preparation of frovatriptan and its enantiomer |
| CN103421855B (zh) * | 2013-08-13 | 2016-04-13 | 凯莱英医药集团（天津）股份有限公司 | 一种制备琥珀酸夫罗曲坦关键中间体的方法 |
| CN104529871A (zh) * | 2014-12-22 | 2015-04-22 | 青岛正大海尔制药有限公司 | 一种琥珀酸呋罗曲坦的制备方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2528267A (en) * | 1950-10-31 | Eobeet j | ||
| NL7514300A (nl) * | 1975-12-09 | 1977-06-13 | Stamicarbon | Werkwijze voor de bereiding van optisch actief fenylglycineamide. |
| JPS6259274A (ja) * | 1985-05-29 | 1987-03-14 | Sumitomo Pharmaceut Co Ltd | 光学活性なフエニルセリン誘導体の製造方法 |
| GB9113802D0 (en) * | 1991-06-26 | 1991-08-14 | Smithkline Beecham Plc | Medicaments |
| US5827871A (en) | 1991-06-26 | 1998-10-27 | Smithkline Beecham Plc | Medicaments 1,2,3,4-tetrahydrocarbazoles and 5-HT1 agonist use thereof |
| US5616603A (en) | 1995-05-26 | 1997-04-01 | Smithkline Beecham Plc | Enantiomers of carbazole derivatives as 5-HT1 -like agonists |
| GB9226530D0 (en) | 1992-12-21 | 1993-02-17 | Smithkline Beecham Plc | Compounds |
| IL110255A (en) * | 1993-07-16 | 1998-12-06 | Merck & Co Inc | Formation and resolution of 2-tert-butylcarboxamido-piperazine |
| JPH07229341A (ja) * | 1994-02-15 | 1995-08-29 | Takero Mori | 観音開き扉用ロック |
| US5618948A (en) | 1995-05-26 | 1997-04-08 | Smithkline Beecham P.L.C. | Process for preparing an enantiomer of a carbazole derivative |
| US5917054A (en) | 1995-07-18 | 1999-06-29 | Smithkline Beecham P.L.C. | Process for preparing enantiomers of carbazole derivatives as 5-HT1 -like agonists |
-
1998
- 1998-04-16 GB GBGB9808069.0A patent/GB9808069D0/en not_active Ceased
-
1999
- 1999-04-16 EA EA200001080A patent/EA004586B1/ru not_active IP Right Cessation
- 1999-04-16 ES ES99915957.7T patent/ES2541432T3/es not_active Expired - Lifetime
- 1999-04-16 AU AU34370/99A patent/AU3437099A/en not_active Abandoned
- 1999-04-16 UA UA2000116417A patent/UA70943C2/uk unknown
- 1999-04-16 AR ARP990101781A patent/AR015771A1/es active IP Right Grant
- 1999-04-16 DK DK99915957.7T patent/DK1070051T3/en active
- 1999-04-16 PT PT99915957T patent/PT1070051E/pt unknown
- 1999-04-16 MY MYPI99001476A patent/MY126530A/en unknown
- 1999-04-16 BR BR9909627-7A patent/BR9909627A/pt not_active Application Discontinuation
- 1999-04-16 YU YU62800A patent/YU62800A/sh unknown
- 1999-04-16 CA CA2328345A patent/CA2328345C/en not_active Expired - Lifetime
- 1999-04-16 HR HRP20000683AA patent/HRP20000683B1/hr not_active IP Right Cessation
- 1999-04-16 KR KR1020007011362A patent/KR100612183B1/ko not_active Expired - Lifetime
- 1999-04-16 SK SK1518-2000A patent/SK286425B6/sk not_active IP Right Cessation
- 1999-04-16 EP EP99915957.7A patent/EP1070051B1/en not_active Expired - Lifetime
- 1999-04-16 ID IDW20002365A patent/ID26783A/id unknown
- 1999-04-16 MX MXPA00010127A patent/MXPA00010127A/es active IP Right Grant
- 1999-04-16 HU HU0101445A patent/HU230559B1/hu unknown
- 1999-04-16 CZ CZ20003823A patent/CZ297303B6/cs not_active IP Right Cessation
- 1999-04-16 SI SI9931077T patent/SI1070051T1/sl unknown
- 1999-04-16 CN CNB998072516A patent/CN1200931C/zh not_active Expired - Lifetime
- 1999-04-16 TR TR2001/00142T patent/TR200100142T2/tr unknown
- 1999-04-16 JP JP2000544643A patent/JP4756740B2/ja not_active Expired - Lifetime
- 1999-04-16 PL PL343528A patent/PL210864B1/pl unknown
- 1999-04-16 EE EEP200000597A patent/EE05156B1/xx unknown
- 1999-04-16 WO PCT/GB1999/001167 patent/WO1999054302A1/en not_active Ceased
- 1999-04-16 IL IL13901799A patent/IL139017A/xx not_active IP Right Cessation
- 1999-05-03 TW TW088107131A patent/TWI255812B/zh active
-
2000
- 2000-10-13 US US09/689,661 patent/US6359146B1/en not_active Expired - Lifetime
- 2000-10-13 NO NO20005158A patent/NO317883B1/no not_active IP Right Cessation
- 2000-11-03 ZA ZA200006303A patent/ZA200006303B/en unknown
-
2015
- 2015-06-23 CY CY20151100532T patent/CY1116418T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2025672B1 (en) | Process for producing 1-carbamoyl-3,7-dioxo-1,4-diazepane compounds | |
| US10421717B2 (en) | Process for preparing brivaracetam | |
| TW200808770A (en) | Novel processes for the preparation of DPP IV inhibitors | |
| HU226475B1 (en) | Process for producing (1r,4s)- and (1s,4r)-1-amino-4-hydroxymethyl-2-cyclopentene and the new intermediates | |
| CN101563329A (zh) | 用于制备4，4’-（1-甲基-1，2-乙二基）-双-（2，6-哌嗪二酮）的新方法 | |
| SK286425B6 (sk) | Spôsob výroby R-(+)-6-karboxamido-3-N-metylamino-1,2,3,4- tetrahydrokarbazolu a použitie kyseliny L-pyroglutámovej | |
| HUP0101335A2 (hu) | Új eljárás N-[(S)-1-karboxibutil]-(S)-alanin-észterek előállítására, és a perindopril szintézisnél történő alkalmazása | |
| WO2024092892A1 (zh) | 依度沙班中间体及其制备方法 | |
| US6979736B2 (en) | Process for the preparation of benazepril hydrochloride | |
| CN118580192B (zh) | 一种治疗高眼压药物手性中间体的制备方法 | |
| US7943784B2 (en) | Process for the preparation of almotriptan | |
| JP2002512227A5 (tr) | ||
| JP2002284761A (ja) | 光学活性３−アミノピロリジン−２，５−ジオン誘導体および光学活性３−アミノピロリジン誘導体の製造方法 | |
| WO1998035934A1 (fr) | DERIVES DE η-OXO-HOMOPHENYLALANINE ET PROCEDE DE PRODUCTION DE DERIVES D'HOMOPHENYLALANINE PAR REDUCTION DE CES DERNIERS | |
| Bonnaud et al. | Stereoselective synthesis of cis and trans 2‐substituted 1‐phenyl‐3‐azabicyclo [3.1. 0] hexanes | |
| JP2002212155A (ja) | 光学活性アスパラギンエステル誘導体、光学活性３−アミノピロリジン−２，５−ジオン誘導体および光学活性３−アミノピロリジン誘導体の製造方法 | |
| HK1037615B (en) | Process for the production of r-(+)-6-carboxamido-3-n- methylamino -1,2,3,4-tetrahydrocarbazole | |
| IE20000060A1 (en) | Novel Process for Producing AMPA Antagonist Compounds | |
| HU198477B (en) | Process for producing pyrimidinyl piperazine derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4A | Expiry of patent |
Expiry date: 20190416 |