公开(公告)号：US20080249311A1

公开(公告)日：2008-10-09

申请号：US12066187

申请日：2006-09-07

申请人： Lixin Wang ,  Yi Tang ,  Yi Chen ,  Fang Tian

发明人： Lixin Wang ,  Yi Tang ,  Yi Chen ,  Fang Tian

IPC分类号： C07D221/02

CPC分类号： C07D495/04 ,  Y02P20/582

摘要： The present invention disclosed a preparation method of Clopidogrel (X=2-Cl) and its analogues of methyl tetrahydrothienopyridine acetate (I) by using halogen phenyl acetonitrile (VIII) as starting material and tetrahydrothienopyridine acetonitrile (IV), tetrahydrothienopyridine acetate (V) as key intermediates, and further using kinetic resolution to prepare the optical active Clopidogrel and compounds of methyl tetrahydrothenopridine acetate of formula (XII). The Clopidogrel of present invention is a novel high effective and safety drug for inhibition of platelet aggregation. This invention applied systematic technique of racemization of unwanted optical active enantiomer, recover recycle and reuse of resolution agent etc., with greater economic advantages and suitable for commercial scale industrial production. Wherein: X represents atoms of hydrogen, fluorine, chlorine, bromine or iodine, M represents an alkali metal ion.

摘要翻译： 本发明公开了以卤代苯基乙腈（Ⅷ）为起始原料和四氢噻吩并吡啶乙腈（Ⅳ），四氢噻吩并吡啶乙酸酯（Ⅴ）为氯化物的氯吡格雷（X = 2-Cl）及其类似物甲基四氢噻吩并吡啶乙酸酯 关键中间体，并进一步使用动力学拆分制备光学活性氯吡格雷和式（XII）的四氢化吖啶甲酸甲酯的化合物。 本发明氯吡格雷是抑制血小板聚集的新型高效安全药物。 本发明应用了不需要的光学活性对映体外消旋化的系统技术，回收再利用分解剂等，具有较大的经济优势，适用于商业规模的工业化生产。 其中X表示氢，氟，氯，溴或碘的原子，M表示碱金属离子。