利伐沙班异丙叉杂质的合成  

Synthesis of Rivaroxaban Isopropylidene Impurity

作　　者：李维思[1] 陈华荣 吴小刚[1] LI Wei-si;CHEN Hua-rong;WU Xiao-gang(Jiangsu Zhongbang Pharmaceutical Co.,Ltd.,Jiangsu Nanjing 211800,China)

机构地区：[1]江苏中邦制药有限公司,江苏南京211800

出　　处：《广州化工》2020年第17期26-27,共2页GuangZhou Chemical Industry

摘　　要：杂质对于药物质量及其安全性至关重要。利伐沙班异丙叉杂质是抗凝药物利伐沙班中一种潜在的工艺杂质。本工作主要报道合成该杂质一种简洁高效的合成方法。以利伐沙班RVXB-3作为起始原料,首先与丙酮异丙叉发生迈克尔加成反应,然后再与5-氯噻吩酰氯发生N-乙酰化反应得到产物,其结构经核磁氢谱确认无误。整个反应高效简洁,所得利伐沙班异丙叉杂质产率高,可以为利伐沙班药物的质量控制提供合格的杂质对照品。Impurity is important for the quality and safety of pharmaceuticals.Rivaroxaban isopropylidene impurity is a possible impurity during the synthesis rivaroxaban.A facile and effective route towards this impurity was reported,involving Michael reaction of isopropylidene with rivaroxaban intermediate of RVXB-3 followed by installing 5-chorothiophene-2-carbonylchloride via N-amidation,which was structurally confirmed by H-NMR spectrum.The overall reaction procedure is simple but efficient,which can provide qualified rivaroxaban isopropylidene impurity for quality control of rivaroxaban.

关 键 词：杂质对照品 利伐沙班 利伐沙班异丙叉杂质 

分 类 号：O622.7[理学—有机化学]