阿哌沙班中间体的合成  

Synthesis of apixaban intermediate

作　　者：王江霞[1] 王盼[1] 刘立云[2] 张赫明 尚振华[1] 

机构地区：[1]河北科技大学化学与制药工程学院,河北石家庄050018 [2]石药集团中奇制药技术(石家庄)有限公司,河北石家庄050035

出　　处：《河北科技大学学报》2014年第4期334-338,共5页Journal of Hebei University of Science and Technology

基　　金：河北省百名优秀创新人才支持计划(Ⅱ)

摘　　要：阿哌沙班是一种新型口服抗凝血药物。以对硝基苯胺和5-氯戊酰氯为原料,依次经过酰化-环合、二氯化、缩合-消除、[3+2]环合-消除反应合成阿哌沙班的关键中间体。该方法4步反应总收率为58.1%,反应所需原料易得,反应条件温和,反应步骤短,产品纯度高达99.5%(HPLC法),为阿哌沙班的合成提供了原料。Apixaban is a novel oral anticoagulant.Synthesis of apixaban intermediate from nitroaniline and 5-chloro-valeryl chloride is described through four steps,including acylation-cyclization,chlorination to the dichloro-intermediate,condensationelimination of the chloro groups and [3＋2] cyclization-elimination.The total yield of the 4-step procedure is 58.1％.The raw materials are easily available,the reaction steps are less,the reaction condition is mild,and the high product purity （by HPLC） reaches 99.5 ％.The procedure provides raw material for synthesis of apixaban.

关 键 词：抗凝血药 阿哌沙班 中间体 合成 

分 类 号：R914.5[医药卫生—药物化学]