摘要
目的合成S构型的氯吡格雷一级氧化产物(S)-2-氧氯吡格雷。方法以R-邻氯扁桃酸甲酯和对硝基苯磺酰氯为起始物,经过亲核取代反应得到中间体R-2-(4-硝基苯磺酰氧基)-2-(2-氯苯基)乙酸甲酯,该中间体与5,6,7,7a-四氢噻吩并[3,2-c]吡啶-2(4H)-酮盐酸盐进行瓦尔登翻转得到高纯度的(S)-2-氧氯吡格雷[(S)-2-(2-氯苯基)-2-(2-氧-7,7a-二氢噻吩并[3,2-c]哌啶-5-(2H,4H,6H)-基)乙酸甲酯]。结果与结论目标化合物的结构经1H-NMR、13C-NMR和IR谱确证,HPLC检测纯度高达99.0%,总收率为5.9%。此工艺路线简单易行、条件温和,仅需2步反应即可得到目标物,适用于实验室小规模合成研究。
The first-order oxidation product of clopidogrel,namely(S)-2-oxo-clopidogrel,was synthesized.First,the intermediate R-2-(4-nitrobenzenesulfonyl)-2-(2-chlorophenyl)methyl acetate was obtained by nucleophilic substitution reaction with R-o-chloromandelic acid methyl ester and p-nitrobenzenesulfonyl chloride and then this intermediate was subjected to Walden turnover with 5,6,7,7 a-tetrahydrothieno[3,2-c]pyridine-2(4H)-one hydrochloride to obtain high purity(S)-2-oxo-clopidogrel[(S)-2-(2-chlorophenyl)-2-(2-oxo-7,7 a-dihydrothieno[3,2-c]piperidine-5-(2H,4H,6H)-yl)methyl acetate].The(S)-2-oxo-clopidogrel obtained in this study was confirmed by 1H-NMR,13C-NMR,and IR.The purity by HPLC was as high as 99.0%,and the total yield was 5.9%.This process not only has a simple synthetic route,mild conditions,but also requires only two steps to obtain the target product,which is suitable for laboratory small-scale synthesis research.
作者
王添艳
刘云
李艳丽
孙增先
WANG Tian-yan;LIU Yun;LI Yan-li;SUN Zeng-xian(Department of Pharmacy,Lianyungang Hospital Affiliated of Xuzhou Medical University/The First People's Hospital of Lianyungang,Lianyungang 222002,China)
出处
《中国药物化学杂志》
CAS
CSCD
北大核心
2020年第7期416-418,427,共4页
Chinese Journal of Medicinal Chemistry
