公开(公告)号：EP1856127A1

公开(公告)日：2007-11-21

申请号：EP06705752.1

申请日：2006-03-03

申请人： Zentiva, a.s.

发明人： HAJICEK, Josef ,  STEPANKOVA, Hana ,  KALIVODA, Jan

IPC分类号： C07D495/04

CPC分类号： C07D495/04

摘要： Racemization of the R(-) isomer of the (2-chlorophenyl) -6, 7-dihydrothieno [3, 2-c]pyridine- 5 (4H) -acetic acid methyl ester (Formula II) (also called R clopidogrel) is performed via conversion of a portion thereof to the S (+) isomer and it takes place in an organic solvent selected from alcohols , esters, ketones or ethers, or in their mixtures, in the presence of a base selected from substances of formula R1R2R3R4N+OH' wherein R1, R2, R3 and R4 are identical or different substituents selected from C1-C5 alkyls or C5, C6 cycloalkyls or aryls, C7-C9 alkyl-cycloalkyls or alkyl-aryls, the molar ratio of the base to the starting substance being 1: 1 to 1: 10. ,OMe Cl I Cl

公开(公告)号：EP1713812A1

公开(公告)日：2006-10-25

申请号：EP04802610.8

申请日：2004-12-21

申请人： Zentiva, a.s.

发明人： HAJICEK, Josef ,  PIHERA, Pavel ,  STEPANKOVA, Hana

IPC分类号： C07D495/04 ,  C07D333/00 ,  C07D221/00

CPC分类号： C07D495/04

摘要： The invention concerns clopidogrel hydrobromide in the crystalline Form I characterized by an X-ray diffraction pattern with characteristic interplanar distances d of 4.01; 4.39 and 3.17 ú and which is further characterized by bands in the infrared spectra at 1743; 1421; 1237, 760 and 728 cm-1. Clopidogrel hydrobromide in the crystalline Form II is characterized by an X­ray diffraction pattern with characteristic interplanar distances d of 4.52; 3.83; 3.48 ú, as well as bands in the infrared spectra at 1754; 1436; 1317 and 1223 cm-1. Crystalline form III is characterized by the following peaks ascertained by X-ray diffraction at 20 positions: 7.796 °; 15.380 °; 18.389 °; 19.369 ° and 23.895 °. The method of preparation of clopidogrel hydrobromide in the crystalline Form I consist in precipitating the clopidogrel base dissolved in toluene with a concentrated solution of hydrobromic acid. The method of preparation of clopidogrel hydrobromide in the crystalline Form II consist in dissolving the clopidogrel base in an organic solvent and precipitating it with a solution of hydrobromic acid in toluene or with gaseous hydrogen bromide. Form III can be used for the preparation of pharmaceutically applicable Form II.

公开(公告)号：EP1554284A1

公开(公告)日：2005-07-20

申请号：EP03750270.5

申请日：2003-08-26

申请人： ZENTIVA, A.S.

发明人： VEVERKA, Miroslav ,  VODNY, Stefan ,  VEVERKOVA, Eva ,  HAJICEK, Josef ,  STEPANKOVA, Hana

IPC分类号： C07D495/04

CPC分类号： C07D495/04

摘要： A method for manufacturing hydrogen sulphate (alpha S) of the alpha-(2-chlorophenyl)-6,7­dihydro-thieno[3,2-c]pyridine-5(4H)-acetic acid methyl ester (clopidogrel hydrogen sulphate) of formula I, in crystalline Form I, wherein the compound of formula is separated out of a solution of clopidogrel in the form of the free base or salt in a solvent selected from the series of primary, secondary or tertiary C1-C5 alcohols, their esters with Cl-C4 carboxylic acids, or optionally of mixtures thereof.

公开(公告)号：EP1554284B1

公开(公告)日：2008-10-22

申请号：EP03750270.5

申请日：2003-08-26

申请人： Zentiva, a.s.

发明人： VEVERKA, Miroslav ,  VODNY, Stefan ,  VEVERKOVA, Eva ,  HAJICEK, Josef ,  STEPANKOVA, Hana

IPC分类号： C07D495/04

CPC分类号： C07D495/04

摘要： A method for manufacturing hydrogen sulphate (alpha S) of the alpha-(2-chlorophenyl)-6,7­dihydro-thieno[3,2-c]pyridine-5(4H)-acetic acid methyl ester (clopidogrel hydrogen sulphate) of formula I, in crystalline Form I, wherein the compound of formula is separated out of a solution of clopidogrel in the form of the free base or salt in a solvent selected from the series of primary, secondary or tertiary C1-C5 alcohols, their esters with Cl-C4 carboxylic acids, or optionally of mixtures thereof.