抗凝血药阿哌沙班的合成  

Synthesis of the Anticoagulant Drug Apixaban

作　　者：张伟[1] 王雪[1] 昌兴龙[1] 李瑛光[1] 萧伟[1] 

机构地区：[1]江苏康缘药业股份有限公司,江苏连云港222001

出　　处：《中国医药工业杂志》2016年第10期1216-1218,共3页Chinese Journal of Pharmaceuticals

摘　　要：2-哌啶酮经双氯取代和缩合-消除反应得3-吗啉-4-基-5,6-二氢-1H-吡啶-2-酮,与1-(4-碘苯基)-2-哌啶酮进行亲核取代反应得5,6-二氢-3-(4-吗啉基)-1-[4-(2-氧代-1-哌啶基)苯基]-2-吡啶酮,继而经1,3偶极环加成、氨解得抗凝血药阿哌沙班,总收率30.2%(以2-哌啶酮计),纯度99.8%。工艺稳定,反应条件温和,操作简便,适宜工业生产。The key intermediate 3-morpholino-5,6-dihydropyridin-2（1H）-one was obtained via dichlorination with 2-piperidone and condensation-elimination, then the intermediate reacted with 1-（4-iodophenyl）piperidin-2-one via nucleophilic substitution, 1,3-dipolar cycloaddition and aminolysis to give the anticoagulant drug apixaban with an overall yield of 30.2%（based on 2-piperidone）and a purity of 99.8%. The process was stable and easy to scale up industrially.

关 键 词：阿哌沙班 抗凝血药 Xa因子直接抑制剂 合成工艺 深静脉血栓 肺栓塞 

分 类 号：R973.2[医药卫生—药品]