HRP20050962A2 - METHOD OF PREPARING (S)-(+)-METHYL α-(2-CHLORPHENYL)-6,7-DIHYDROTIENO[3,2-c]PYRIDINE-5(4H)-ACETATE HYDROGENSULFATE OF GREAT ENANTIOMER PURITY - Google Patents
METHOD OF PREPARING (S)-(+)-METHYL α-(2-CHLORPHENYL)-6,7-DIHYDROTIENO[3,2-c]PYRIDINE-5(4H)-ACETATE HYDROGENSULFATE OF GREAT ENANTIOMER PURITYInfo
- Publication number
- HRP20050962A2 HRP20050962A2 HR20050962A HRP20050962A HRP20050962A2 HR P20050962 A2 HRP20050962 A2 HR P20050962A2 HR 20050962 A HR20050962 A HR 20050962A HR P20050962 A HRP20050962 A HR P20050962A HR P20050962 A2 HRP20050962 A2 HR P20050962A2
- Authority
- HR
- Croatia
- Prior art keywords
- clopidogrel
- methyl
- purity
- hydrogensulfate
- dihydrotieno
- Prior art date
Links
- 238000000034 method Methods 0.000 title abstract 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 title 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 abstract 5
- 229950010477 clopidogrel hydrogen sulphate Drugs 0.000 abstract 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 abstract 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract 3
- 239000000126 substance Substances 0.000 abstract 3
- 238000002425 crystallisation Methods 0.000 abstract 2
- 230000008025 crystallization Effects 0.000 abstract 2
- 239000012442 inert solvent Substances 0.000 abstract 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 abstract 2
- 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 abstract 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 abstract 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 abstract 1
- 229930040373 Paraformaldehyde Natural products 0.000 abstract 1
- 239000004280 Sodium formate Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 abstract 1
- 229960003009 clopidogrel Drugs 0.000 abstract 1
- 235000019253 formic acid Nutrition 0.000 abstract 1
- 229960001269 glycine hydrochloride Drugs 0.000 abstract 1
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 230000003287 optical effect Effects 0.000 abstract 1
- 229920002866 paraformaldehyde Polymers 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 238000007363 ring formation reaction Methods 0.000 abstract 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 abstract 1
- 235000019254 sodium formate Nutrition 0.000 abstract 1
Landscapes
- Pyridine Compounds (AREA)
Abstract
Izum se odnosi na postupak za dobivanje (S)-clopidogrel hidrogensulfata (S-1) visoke kemijske i enantiomerne čistoće ciklizacijom (S)-metil α-(2-(2-tiofenil)etil)(2-klorfenil)glicin hidroklorida(S-2) s paraformaldehidom u prisustvu natrijeva formijata u smjesi mravlje kiseline i inertnog otapala pri čemu nastaje clopidogrel baza visoke kemijske čistoće uz potpuno očuvanje enantiomerne čistoće. Tako pripravljena (S)-clopidogrel baza prevodise u hidrogensulfatnu sol reakcijom sa sulfatnom kiselinom u metiletilketonu. Sirovi (S)-clopidogrel hidrogensulfat enantiomerno se obogaćuje kristalizacijom racemičnog clopidogrel hidrogensulfata izmetanola, dok se naknadno (S)-clopidogrel hidrogensulfat vrlo visoke (99.8%) kemijske i optičke čistoće dobiva kristalizacijom iz metanola pomoću različitih inertnih otapala.The invention relates to a process for the preparation of (S) -clopidogrel hydrogen sulphate (S-1) of high chemical and enantiomeric purity by cyclization of (S) -methyl α- (2- (2-thiophenyl) ethyl) (2-chlorophenyl) glycine hydrochloride (S -2) with paraformaldehyde in the presence of sodium formate in a mixture of formic acid and an inert solvent to form a clopidogrel base of high chemical purity while fully maintaining the enantiomeric purity. The (S) -clopidogrel base thus prepared is converted to the hydrogen sulfate salt by reaction with sulfuric acid in methylethylketone. The crude (S) -clopidogrel hydrogensulfate is enantiomerically enriched by crystallization of racemic clopidogrel hydrogensulfate ismethanol, while the subsequent (S) -clopidogrel hydrogensulfate is obtained by crystallization from methanol using various inert solvents of very high (99.8%) chemical and optical purity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HR20050962A HRP20050962A2 (en) | 2005-11-18 | 2005-11-18 | METHOD OF PREPARING (S)-(+)-METHYL α-(2-CHLORPHENYL)-6,7-DIHYDROTIENO[3,2-c]PYRIDINE-5(4H)-ACETATE HYDROGENSULFATE OF GREAT ENANTIOMER PURITY |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HR20050962A HRP20050962A2 (en) | 2005-11-18 | 2005-11-18 | METHOD OF PREPARING (S)-(+)-METHYL α-(2-CHLORPHENYL)-6,7-DIHYDROTIENO[3,2-c]PYRIDINE-5(4H)-ACETATE HYDROGENSULFATE OF GREAT ENANTIOMER PURITY |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20050962A2 true HRP20050962A2 (en) | 2007-05-31 |
Family
ID=38121719
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20050962A HRP20050962A2 (en) | 2005-11-18 | 2005-11-18 | METHOD OF PREPARING (S)-(+)-METHYL α-(2-CHLORPHENYL)-6,7-DIHYDROTIENO[3,2-c]PYRIDINE-5(4H)-ACETATE HYDROGENSULFATE OF GREAT ENANTIOMER PURITY |
Country Status (1)
| Country | Link |
|---|---|
| HR (1) | HRP20050962A2 (en) |
-
2005
- 2005-11-18 HR HR20050962A patent/HRP20050962A2/en not_active Application Discontinuation
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