NO325305B1 - Nye mellomprodukter, isomerer derav og fremgangsmate for fremstilling av disse - Google Patents
Nye mellomprodukter, isomerer derav og fremgangsmate for fremstilling av disse Download PDFInfo
- Publication number
- NO325305B1 NO325305B1 NO19995531A NO995531A NO325305B1 NO 325305 B1 NO325305 B1 NO 325305B1 NO 19995531 A NO19995531 A NO 19995531A NO 995531 A NO995531 A NO 995531A NO 325305 B1 NO325305 B1 NO 325305B1
- Authority
- NO
- Norway
- Prior art keywords
- general formula
- chlorophenyl
- thienyl
- ethylamino
- mol
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 239000000543 intermediate Substances 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 24
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000000203 mixture Substances 0.000 claims description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 18
- 230000003287 optical effect Effects 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 10
- JXMUSLFGOYRHHE-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetonitrile Chemical group ClC1=CC=CC=C1C(C#N)NCCC1=CC=CS1 JXMUSLFGOYRHHE-UHFFFAOYSA-N 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- HLTBXUWKIUQAJX-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetonitrile;hydrochloride Chemical group Cl.ClC1=CC=CC=C1C(C#N)NCCC1=CC=CS1 HLTBXUWKIUQAJX-UHFFFAOYSA-N 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 150000001340 alkali metals Chemical group 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 4
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims description 2
- 239000012736 aqueous medium Substances 0.000 claims 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 abstract description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 abstract 2
- 239000003513 alkali Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- 239000000047 product Substances 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 239000013078 crystal Substances 0.000 description 14
- 238000000921 elemental analysis Methods 0.000 description 14
- 238000002329 infrared spectrum Methods 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 238000001816 cooling Methods 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- WTLWYLDVLAIHPU-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetamide Chemical compound C=1C=CC=C(Cl)C=1C(C(=O)N)NCCC1=CC=CS1 WTLWYLDVLAIHPU-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 8
- 229940011051 isopropyl acetate Drugs 0.000 description 8
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- GKTWGGQPFAXNFI-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)acetic acid methyl ester Chemical compound C1CC=2SC=CC=2CN1C(C(=O)OC)C1=CC=CC=C1Cl GKTWGGQPFAXNFI-UHFFFAOYSA-N 0.000 description 5
- 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 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- ZXANKCFSGFEBQW-UHFFFAOYSA-N methyl 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetate;hydrochloride Chemical compound Cl.C=1C=CC=C(Cl)C=1C(C(=O)OC)NCCC1=CC=CS1 ZXANKCFSGFEBQW-UHFFFAOYSA-N 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- ALLFNKNHKLXYSI-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetamide;hydron;chloride Chemical compound Cl.C=1C=CC=C(Cl)C=1C(C(=O)N)NCCC1=CC=CS1 ALLFNKNHKLXYSI-UHFFFAOYSA-N 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 238000010908 decantation Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- HVLUYXIJZLDNIS-UHFFFAOYSA-N 2-thiophen-2-ylethanamine Chemical compound NCCC1=CC=CS1 HVLUYXIJZLDNIS-UHFFFAOYSA-N 0.000 description 3
- 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 compound 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 3
- 239000001358 L(+)-tartaric acid Substances 0.000 description 3
- 235000011002 L(+)-tartaric acid Nutrition 0.000 description 3
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 3
- MIOPJNTWMNEORI-MHPPCMCBSA-N [(4r)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-MHPPCMCBSA-N 0.000 description 3
- -1 [2-(2-thienyl)ethylamino] (2-chlorophenyl)- Chemical class 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 2
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 2
- 229960003009 clopidogrel Drugs 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000002050 international nonproprietary name Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- PAOGEKGFTGONII-UHFFFAOYSA-N methyl 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetate Chemical compound C=1C=CC=C(Cl)C=1C(C(=O)OC)NCCC1=CC=CS1 PAOGEKGFTGONII-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007790 solid phase Substances 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
- CJPVPOYTTALCNX-UHFFFAOYSA-N (2-chlorophenyl) acetate Chemical compound CC(=O)OC1=CC=CC=C1Cl CJPVPOYTTALCNX-UHFFFAOYSA-N 0.000 description 1
- GAQWDBUWBUOFLS-UHFFFAOYSA-N (7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methanesulfonic acid;hydrate Chemical compound O.C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C GAQWDBUWBUOFLS-UHFFFAOYSA-N 0.000 description 1
- XEENARPWPCQXST-UHFFFAOYSA-N (7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methanesulfonic acid;methyl 2-(2-chlorophenyl)-2-(6,7-dihydro-4h-thieno[3,2-c]pyridin-5-yl)acetate Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C.C1CC=2SC=CC=2CN1C(C(=O)OC)C1=CC=CC=C1Cl XEENARPWPCQXST-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- BNIBRYOCUPIMAA-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetamide;hydrobromide Chemical compound Br.C=1C=CC=C(Cl)C=1C(C(=O)N)NCCC1=CC=CS1 BNIBRYOCUPIMAA-UHFFFAOYSA-N 0.000 description 1
- ALXLPLAPCNENNE-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetonitrile;hydrobromide Chemical compound Br.ClC1=CC=CC=C1C(C#N)NCCC1=CC=CS1 ALXLPLAPCNENNE-UHFFFAOYSA-N 0.000 description 1
- MRDUURPIPLIGQX-UHFFFAOYSA-N 2-(2-chlorophenyl)acetonitrile Chemical compound ClC1=CC=CC=C1CC#N MRDUURPIPLIGQX-UHFFFAOYSA-N 0.000 description 1
- XHAPROULWZYBGA-UHFFFAOYSA-N 2-bromo-2-(2-chlorophenyl)acetic acid Chemical compound OC(=O)C(Br)C1=CC=CC=C1Cl XHAPROULWZYBGA-UHFFFAOYSA-N 0.000 description 1
- ZZLKPFGLOQUCNC-UHFFFAOYSA-N 2-thiophen-2-ylethanamine;hydrochloride Chemical compound Cl.NCCC1=CC=CS1 ZZLKPFGLOQUCNC-UHFFFAOYSA-N 0.000 description 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- HDRXZJPWHTXQRI-BHDTVMLSSA-N diltiazem hydrochloride Chemical compound [Cl-].C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CC[NH+](C)C)C2=CC=CC=C2S1 HDRXZJPWHTXQRI-BHDTVMLSSA-N 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N dimethylacetone Natural products CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- FDEODCTUSIWGLK-UHFFFAOYSA-N hydrogen sulfate;hydron;methyl 2-(2-chlorophenyl)-2-(6,7-dihydro-4h-thieno[3,2-c]pyridin-5-yl)acetate Chemical compound OS(O)(=O)=O.C1CC=2SC=CC=2CN1C(C(=O)OC)C1=CC=CC=C1Cl FDEODCTUSIWGLK-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- XIHVAFJSGWDBGA-RSAXXLAASA-N methyl (2s)-2-(2-chlorophenyl)-2-(6,7-dihydro-4h-thieno[3,2-c]pyridin-5-yl)acetate;hydrochloride Chemical compound Cl.C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl XIHVAFJSGWDBGA-RSAXXLAASA-N 0.000 description 1
- VCSVITJHVCIXQV-UHFFFAOYSA-N methyl 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetate;hydrobromide Chemical compound Br.C=1C=CC=C(Cl)C=1C(C(=O)OC)NCCC1=CC=CS1 VCSVITJHVCIXQV-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- GLQWRXYOTXRDNH-UHFFFAOYSA-N thiophen-2-amine Chemical compound NC1=CC=CS1 GLQWRXYOTXRDNH-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9700886A HU225504B1 (en) | 1997-05-13 | 1997-05-13 | Novel halophenyl-(2-(2-thienyl)-ethylamino)-acetonitriles and process for producing them |
| PCT/HU1998/000046 WO1998051682A1 (fr) | 1997-05-13 | 1998-05-11 | Nouveaux produits intermediaires et procede de preparation de ces derniers |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO995531D0 NO995531D0 (no) | 1999-11-12 |
| NO995531L NO995531L (no) | 1999-12-13 |
| NO325305B1 true NO325305B1 (no) | 2008-03-25 |
Family
ID=89995121
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19995531A NO325305B1 (no) | 1997-05-13 | 1999-11-12 | Nye mellomprodukter, isomerer derav og fremgangsmate for fremstilling av disse |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US6215005B1 (fr) |
| EP (1) | EP0981525B1 (fr) |
| JP (1) | JP4279903B2 (fr) |
| AT (1) | ATE258551T1 (fr) |
| AU (1) | AU7444698A (fr) |
| BR (1) | BR9809113B1 (fr) |
| CA (1) | CA2288637C (fr) |
| DE (1) | DE69821347T2 (fr) |
| DK (1) | DK0981525T3 (fr) |
| ES (1) | ES2213900T3 (fr) |
| HU (1) | HU225504B1 (fr) |
| NO (1) | NO325305B1 (fr) |
| PT (1) | PT981525E (fr) |
| WO (1) | WO1998051682A1 (fr) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU226421B1 (en) * | 1998-11-09 | 2008-12-29 | Sanofi Aventis | Process for racemizing optically active 2-(2-chlorophenyl)-2-(2-(2-thienyl)-ethylamino)-acetamides |
| US6495691B1 (en) | 2001-07-06 | 2002-12-17 | Brantford Chemicals Inc. | Process for the preparation of tetrahydrothieno[3,2-c]pyridine derivatives |
| US6767913B2 (en) | 2001-12-18 | 2004-07-27 | Teva Pharmaceutical Industries Ltd. | Crystal forms iii, iv, v, and novel amorphous form of clopidogrel hydrogensulfate, processes for their preparation, processes for the preparation of form i, compositions containing the new forms and methods of administering the new forms |
| US7074928B2 (en) | 2002-01-11 | 2006-07-11 | Teva Pharmaceutical Industries, Ltd. | Polymorphs of clopidogrel hydrogensulfate |
| HUP0200438A3 (en) * | 2002-02-06 | 2003-10-28 | Egis Gyogyszergyar Nyilvanosan | Novel clopidogrel hydrochloride polymorphs, process for the preparation thereof, their use and pharmaceutical compositions containing them |
| IL166593A0 (en) | 2002-08-02 | 2006-01-15 | Racemization and enantiomer separation of clopidogrel | |
| US6800759B2 (en) * | 2002-08-02 | 2004-10-05 | Teva Pharmaceutical Industries Ltd. | Racemization and enantiomer separation of clopidogrel |
| EP1603920A1 (fr) | 2003-03-12 | 2005-12-14 | Cadila Healthcare Ltd. | Polymorphes et forme amorphe de bisulfate de (s) - (+) -clopidogrel |
| US20040250673A1 (en) * | 2003-06-10 | 2004-12-16 | Salerno Paul Michael | Ergonomic pedal board |
| GB0321256D0 (en) | 2003-09-11 | 2003-10-08 | Generics Uk Ltd | Novel crystalline compounds |
| EP1680430B1 (fr) | 2003-11-03 | 2010-01-20 | Cadila Healthcare Ltd. | Procedes de preparation de forme i de (s)-(+)- clopidogrel bisulfate |
| US20060154957A1 (en) * | 2004-09-21 | 2006-07-13 | Nina Finkelstein | Crystalline clopidogrel hydrobromide and processes for preparation thereof |
| TW200640932A (en) * | 2005-02-24 | 2006-12-01 | Teva Pharma | Clopidogrel base suitable for pharmaceutical formulation and preparation thereof |
| EP1902058A2 (fr) | 2005-07-12 | 2008-03-26 | RPG Life Sciences Limited | Procede de preparation d'ester methylique de l'acide methyl-(+)-(s)-alpha-(2-chlorophenyl)-6,7-dihydrothienoý3,2-c¨pyridine-5(4h)-acetique ou de sels dudit acide ayant une purete chirale elevee et produits ainsi obtenus |
| KR20090013794A (ko) * | 2006-04-27 | 2009-02-05 | 인드-스위프트 래버러토리즈 리미티드 | 클로피도그렐 히드로겐 설페이트의 다형태의 제조방법 |
| US20090247569A1 (en) * | 2006-08-03 | 2009-10-01 | Claude Singer | Process for Preparing Clopidogrel Bisulphate |
| EP1980563A1 (fr) | 2007-04-09 | 2008-10-15 | BATTULA, Srinivasa Reddy | Procédure pour la préparation d'acétate de méthyle (+)-(S)-alpha-(O-chlorophényl)-6,7-dihydrothiéno-[3,2-C]pyridine-5(4H) |
| EP2346879A1 (fr) * | 2008-10-24 | 2011-07-27 | Sandoz AG | Procédé de préparation de s-clopidogrel |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2508455A1 (fr) | 1981-06-30 | 1982-12-31 | Sanofi Sa | Procede de preparation de derives des (thienyl-2)- et (thienyl-3)-2 ethylamines |
| FR2530247B1 (fr) | 1982-07-13 | 1986-05-16 | Sanofi Sa | Nouveaux derives de la thieno (3, 2-c) pyridine, leur procede de preparation et leur application therapeutique |
| FR2608607B1 (fr) | 1986-12-23 | 1989-04-28 | Sanofi Sa | Procede de preparation de thienylethylamines et dithienylethylamines ainsi obtenues |
| FR2623810B2 (fr) | 1987-02-17 | 1992-01-24 | Sanofi Sa | Sels de l'alpha-(tetrahydro-4,5,6,7 thieno(3,2-c) pyridyl-5) (chloro-2 phenyl) -acetate de methyle dextrogyre et compositions pharmaceutiques en contenant |
| FR2614619B1 (fr) | 1987-04-29 | 1989-09-15 | Sanofi Sa | Procede de preparation de n-((chloro-2)-benzyl) (thienyl-2)-2 ethylamine |
| FR2652575B1 (fr) * | 1989-09-29 | 1992-01-24 | Sanofi Sa | Procede de preparation d'acides alpha-bromo phenylacetiques. |
| FR2664596B1 (fr) * | 1990-07-10 | 1994-06-10 | Sanofi Sa | Procede de preparation d'un derive n-phenylacetique de tetrahydrothieno [3,2-c] pyridine et son intermediaire de synthese. |
| CA2265886A1 (fr) * | 1996-09-12 | 1998-03-19 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Preparation stereospecifique de 1-aryl- et 1-heteroaryl-2-substituees ethyl-2-amines chirales |
-
1997
- 1997-05-13 HU HU9700886A patent/HU225504B1/hu unknown
-
1998
- 1998-05-11 EP EP98921668A patent/EP0981525B1/fr not_active Expired - Lifetime
- 1998-05-11 AU AU74446/98A patent/AU7444698A/en not_active Abandoned
- 1998-05-11 JP JP54895498A patent/JP4279903B2/ja not_active Expired - Lifetime
- 1998-05-11 DK DK98921668T patent/DK0981525T3/da active
- 1998-05-11 US US09/423,548 patent/US6215005B1/en not_active Expired - Lifetime
- 1998-05-11 AT AT98921668T patent/ATE258551T1/de active
- 1998-05-11 DE DE69821347T patent/DE69821347T2/de not_active Expired - Lifetime
- 1998-05-11 WO PCT/HU1998/000046 patent/WO1998051682A1/fr active IP Right Grant
- 1998-05-11 CA CA002288637A patent/CA2288637C/fr not_active Expired - Lifetime
- 1998-05-11 BR BRPI9809113-1A patent/BR9809113B1/pt not_active IP Right Cessation
- 1998-05-11 PT PT98921668T patent/PT981525E/pt unknown
- 1998-05-11 ES ES98921668T patent/ES2213900T3/es not_active Expired - Lifetime
-
1999
- 1999-11-12 NO NO19995531A patent/NO325305B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| HUP9700886A2 (hu) | 1999-09-28 |
| NO995531D0 (no) | 1999-11-12 |
| BR9809113A (pt) | 2000-08-01 |
| AU7444698A (en) | 1998-12-08 |
| US6215005B1 (en) | 2001-04-10 |
| NO995531L (no) | 1999-12-13 |
| DE69821347D1 (de) | 2004-03-04 |
| EP0981525B1 (fr) | 2004-01-28 |
| PT981525E (pt) | 2004-05-31 |
| ES2213900T3 (es) | 2004-09-01 |
| HU225504B1 (en) | 2007-01-29 |
| DE69821347T2 (de) | 2004-12-02 |
| WO1998051682A1 (fr) | 1998-11-19 |
| JP2001525817A (ja) | 2001-12-11 |
| BR9809113B1 (pt) | 2010-03-09 |
| EP0981525A1 (fr) | 2000-03-01 |
| CA2288637C (fr) | 2005-11-15 |
| DK0981525T3 (da) | 2004-05-10 |
| CA2288637A1 (fr) | 1998-11-19 |
| ATE258551T1 (de) | 2004-02-15 |
| JP4279903B2 (ja) | 2009-06-17 |
| HU9700886D0 (en) | 1997-07-28 |
| HUP9700886A3 (en) | 2000-06-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |