NO324039B1 - Nye mellomprodukter og fremgangsmate for fremstilling derav - Google Patents

Nye mellomprodukter og fremgangsmate for fremstilling derav Download PDF

Info

Publication number: NO324039B1
Authority: NO; Norway
Prior art keywords: chlorophenyl; thienyl; general formula; ethylamino; salts
Prior art date: 1997-05-13

Application number

NO19995532A

Other languages

English (en)

Norwegian (no)

Other versions

NO995532L (no

NO995532D0 (no

Inventor

Maria Bakonyi

Marianna Csatarine Nagy

Leventene Molnar

Zoltan Makovi

Piroska Jobb

Tiborne Bai

Original Assignee

Sanofi Aventis

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-05-13

Filing date

1999-11-12

Publication date

2007-07-30

1999-11-12 Application filed by Sanofi Aventis filed Critical Sanofi Aventis

1999-11-12 Publication of NO995532D0 publication Critical patent/NO995532D0/no

1999-12-13 Publication of NO995532L publication Critical patent/NO995532L/no

2007-07-30 Publication of NO324039B1 publication Critical patent/NO324039B1/no

Links

238000000034 method Methods 0.000 title claims description 14
238000002360 preparation method Methods 0.000 title claims description 5
239000000543 intermediate Substances 0.000 title description 5
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 72
150000001875 compounds Chemical class 0.000 claims description 36
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 30
150000003839 salts Chemical class 0.000 claims description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 14
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 14
230000003287 optical effect Effects 0.000 claims description 13
WTLWYLDVLAIHPU-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetamide Chemical group C=1C=CC=C(Cl)C=1C(C(=O)N)NCCC1=CC=CS1 WTLWYLDVLAIHPU-UHFFFAOYSA-N 0.000 claims description 12
238000006243 chemical reaction Methods 0.000 claims description 11
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 7
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 7
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 7
235000019253 formic acid Nutrition 0.000 claims description 7
ALLFNKNHKLXYSI-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetamide;hydron;chloride Chemical group Cl.C=1C=CC=C(Cl)C=1C(C(=O)N)NCCC1=CC=CS1 ALLFNKNHKLXYSI-UHFFFAOYSA-N 0.000 claims description 6
239000001358 L(+)-tartaric acid Substances 0.000 claims description 6
235000011002 L(+)-tartaric acid Nutrition 0.000 claims description 6
FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 claims description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 6
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
239000003960 organic solvent Substances 0.000 claims description 3
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 42
239000000047 product Substances 0.000 description 39
239000000203 mixture Substances 0.000 description 31
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
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
239000002244 precipitate Substances 0.000 description 11
239000007858 starting material Substances 0.000 description 11
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
238000005481 NMR spectroscopy Methods 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
238000003756 stirring Methods 0.000 description 9
239000000463 material Substances 0.000 description 8
JXMUSLFGOYRHHE-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetonitrile Chemical compound ClC1=CC=CC=C1C(C#N)NCCC1=CC=CS1 JXMUSLFGOYRHHE-UHFFFAOYSA-N 0.000 description 7
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
229910000041 hydrogen chloride Inorganic materials 0.000 description 7
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 7
229940011051 isopropyl acetate Drugs 0.000 description 7
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
239000007789 gas Substances 0.000 description 6
238000010992 reflux Methods 0.000 description 6
238000005160 1H NMR spectroscopy Methods 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
230000015572 biosynthetic process Effects 0.000 description 5
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 5
238000001914 filtration Methods 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
235000011121 sodium hydroxide Nutrition 0.000 description 5
229940083608 sodium hydroxide Drugs 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
HLTBXUWKIUQAJX-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-(2-thiophen-2-ylethylamino)acetonitrile;hydrochloride Chemical compound Cl.ClC1=CC=CC=C1C(C#N)NCCC1=CC=CS1 HLTBXUWKIUQAJX-UHFFFAOYSA-N 0.000 description 4
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 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
239000012044 organic layer Substances 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
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
239000002253 acid Substances 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
239000010410 layer Substances 0.000 description 3
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 3
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 2
FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 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
-1 alkyl acetates 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
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
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
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
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
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
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-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
150000007513 acids 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
239000012230 colorless oil Substances 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
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
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 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
QSIRBWSLGOGWCR-UHFFFAOYSA-N methyl 2-(2-chlorophenyl)-2-(6,7-dihydro-4h-thieno[3,2-c]pyridin-5-yl)acetate;hydrate;hydrochloride Chemical compound O.Cl.C1CC=2SC=CC=2CN1C(C(=O)OC)C1=CC=CC=C1Cl QSIRBWSLGOGWCR-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 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
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 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
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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Press Drives And Press Lines (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Steroid Compounds (AREA)

NO19995532A 1997-05-13 1999-11-12 Nye mellomprodukter og fremgangsmate for fremstilling derav NO324039B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
HU9700884A HU225503B1 (en)	1997-05-13	1997-05-13	Novel 2-(2-halophenyl)-2-(2-(2-thienyl)-ethylamino)-acetamides and process for producing them
PCT/HU1998/000047 WO1998051681A1 (en)	1997-05-13	1998-05-11	New intermediates and process for the preparation thereof

Publications (3)

Publication Number	Publication Date
NO995532D0 NO995532D0 (no)	1999-11-12
NO995532L NO995532L (no)	1999-12-13
NO324039B1 true NO324039B1 (no)	2007-07-30

Family

ID=89995117

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19995532A NO324039B1 (no)	1997-05-13	1999-11-12	Nye mellomprodukter og fremgangsmate for fremstilling derav

Country Status (13)

Country	Link
US (1)	US6258961B1 (de)
EP (1)	EP0981524B1 (de)
JP (1)	JP4282770B2 (de)
AT (1)	ATE238294T1 (de)
AU (1)	AU7444798A (de)
BR (1)	BR9809111B1 (de)
CA (1)	CA2289545C (de)
DE (1)	DE69813792T2 (de)
ES (1)	ES2195335T3 (de)
HU (1)	HU225503B1 (de)
NO (1)	NO324039B1 (de)
PT (1)	PT981524E (de)
WO (1)	WO1998051681A1 (de)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
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
GB0125708D0 (en) *	2001-10-26	2001-12-19	Generics Uk Ltd	Novel compounds and processes
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
US6800759B2 (en)	2002-08-02	2004-10-05	Teva Pharmaceutical Industries Ltd.	Racemization and enantiomer separation of clopidogrel
IL166593A0 (en)	2002-08-02	2006-01-15		Racemization and enantiomer separation of clopidogrel
AU2003238664A1 (en)	2003-03-12	2004-09-30	Cadila Healthcare Limited	Polymorphs and amorphous form of (s) - (+) -clopidogrel bisulfate
US6858734B2 (en) *	2003-04-23	2005-02-22	Rhodia Pharma Solutions Inc.	Preparation of (S)-Clopidogrel and related compounds
WO2004108665A2 (en) *	2003-04-24	2004-12-16	Sun Pharmaceutical Industries Limited	A process for preparation of clopidogrel
GB0321256D0 (en)	2003-09-11	2003-10-08	Generics Uk Ltd	Novel crystalline compounds
PL1680430T3 (pl)	2003-11-03	2010-06-30	Cadila Healthcare Ltd	Sposoby wytwarzania postaci i (s)-(+)-wodorosiarczanu klopidogrelu
PL1589019T3 (pl) *	2004-04-20	2008-12-31	Ratiopharm Gmbh	Stereoselektywny sposób wytwarzania klopidogrelu
KR20070052780A (ko) *	2004-09-21	2007-05-22	테바 파마슈티컬 인더스트리즈 리미티드	결정질 클로피도그렐 브롬산염 및 이의 제조 방법
EP1851231A2 (de) *	2005-02-24	2007-11-07	Teva Pharmaceutical Industries Ltd	Zur pharmazeutischen formulierung geeignete clopidogrel-basis und deren herstellung
US20090099363A1 (en) *	2006-04-27	2009-04-16	Saxena Rahul	Process for the preparation of polymorphic forms of clopidogrel hydrogen sulfate
EP1931682A2 (de) *	2006-08-03	2008-06-18	Teva Pharmaceutical Industries Ltd.	Verfahren zur herstellung von clopidogrel-bisulphat
PL382055A1 (pl) *	2007-03-23	2008-09-29	Koźluk Tomasz Nobilus Ent	Sposób wytwarzania formy krystalicznej 1 wodorosiarczanu klopidogrelu
EP1980563A1 (de)	2007-04-09	2008-10-15	BATTULA, Srinivasa Reddy	Verfahren zur Herstellung von Methyl (+)-(S)-Alpha-(O-Chlorophenyl)-6,7-Dihydrothieno-[3,2-C]pyridine-5(4H) Acetat
EP2107061A1 (de)	2008-04-02	2009-10-07	Krka Tovarna Zdravil, D.D., Novo Mesto	Herstellungsverfahren für optisch angereichertes Clopidogrel
US20090264460A1 (en) *	2008-04-21	2009-10-22	Mamta Mishra	Clopidogrel pharmaceutical formulations
WO2010046476A1 (en) *	2008-10-24	2010-04-29	Sandoz Ag	A process for the preparation of s-clopidogrel
US8563690B2 (en) *	2008-11-03	2013-10-22	The Board Of Trustees Of The University Of Illinois	Modulation of platelet aggregation
CN103483356B (zh) *	2013-09-30	2016-01-13	浙江美诺华药物化学有限公司	一种（s）-氯吡格雷的硫酸盐或盐酸盐的制备方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
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.

1997
- 1997-05-13 HU HU9700884A patent/HU225503B1/hu unknown
1998
- 1998-05-11 CA CA002289545A patent/CA2289545C/en not_active Expired - Fee Related
- 1998-05-11 WO PCT/HU1998/000047 patent/WO1998051681A1/en not_active Ceased
- 1998-05-11 EP EP98921669A patent/EP0981524B1/de not_active Expired - Lifetime
- 1998-05-11 DE DE69813792T patent/DE69813792T2/de not_active Expired - Lifetime
- 1998-05-11 AU AU74447/98A patent/AU7444798A/en not_active Abandoned
- 1998-05-11 BR BRPI9809111-5A patent/BR9809111B1/pt not_active IP Right Cessation
- 1998-05-11 ES ES98921669T patent/ES2195335T3/es not_active Expired - Lifetime
- 1998-05-11 AT AT98921669T patent/ATE238294T1/de active
- 1998-05-11 PT PT98921669T patent/PT981524E/pt unknown
- 1998-05-11 JP JP54895598A patent/JP4282770B2/ja not_active Expired - Lifetime
- 1998-05-11 US US09/423,801 patent/US6258961B1/en not_active Expired - Lifetime
1999
- 1999-11-12 NO NO19995532A patent/NO324039B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
NO995532L (no)	1999-12-13
BR9809111B1 (pt)	2009-05-05
AU7444798A (en)	1998-12-08
DE69813792T2 (de)	2004-01-29
JP2001525818A (ja)	2001-12-11
EP0981524B1 (de)	2003-04-23
HU225503B1 (en)	2007-01-29
CA2289545A1 (en)	1998-11-19
CA2289545C (en)	2006-12-12
NO995532D0 (no)	1999-11-12
HUP9700884A2 (hu)	1999-09-28
WO1998051681A1 (en)	1998-11-19
EP0981524A1 (de)	2000-03-01
US6258961B1 (en)	2001-07-10
ATE238294T1 (de)	2003-05-15
ES2195335T3 (es)	2003-12-01
PT981524E (pt)	2003-08-29
BR9809111A (pt)	2000-08-01
JP4282770B2 (ja)	2009-06-24
HUP9700884A3 (en)	2000-06-28
DE69813792D1 (de)	2003-05-28
HU9700884D0 (en)	1997-07-28

Legal Events

Date	Code	Title	Description
2018-06-11	MK1K	Patent expired

Publication	Publication Date	Title
NO325419B1 (no)	2008-04-21	Ny fremgangsmate for fremstilling av en farmakologisk aktiv substans
EP0981524B1 (de)	2003-04-23	Zwischenprodukte und verfahren zu ihrer herstellung
NO325305B1 (no)	2008-03-25	Nye mellomprodukter, isomerer derav og fremgangsmate for fremstilling av disse
RS58799B1 (sr)	2019-07-31	Klizni zatvarač na odvodu kontejnera koji sadrži rastopljeni metal kao i postupak postavljanja zatvornih ploča u klizni zatvarač
JP4598276B2 (ja)	2010-12-15	ラセミ化方法
JP4256478B6 (ja)	2013-04-10	薬理学的に活性な物質の新規調製方法
MXPA99010433A (en)	2000-06-01	New intermediates and process for the preparation thereof
MXPA99010431A (en)	2000-08-01	New intermediates and process for the preparation thereof
MXPA99010434A (en)	2000-08-01	A new process for the preparation of a pharmacologically active substance
MXPA01004644A (en)	2002-03-26	Process for racemization