血栓栓塞性疾病药物达比加群酯的合成工艺研究  

Study on the Synthesis Process of Dabigatran Ester,a Drug for Thromboembolic Diseases

作　　者：孙九德 Sun Jiude(Chiatai Tianqing Pharmaceutical Group Co.,Ltd.,Lianyungang Jiangsu 222000,China)

机构地区：[1]正大天晴药业集团股份有限公司,江苏连云港222000

出　　处：《山西化工》2024年第6期15-17,共3页Shanxi Chemical Industry

摘　　要：研究血栓栓塞性疾病药物达比加群酯的合成工艺,提高达比加群酯的反应收率与提取纯度。基于达比加群酯概述与基本合成方法,对达比加群酯的合成工艺进行改进;通过反复实验确定最优反应条件。实验表明:在1.5 eq乙酰氯下醇解、20℃的温度下氨解,3.0 eq对甲苯磺酸成盐的条件得到化合物2和以二氯甲烷作为反应溶剂得到化合物3,可以节约投入成本,提高反应收率和提取纯度。Study the synthesis process of the drug dabigatran ester for thromboembolic diseases,and improve the reaction yield and extraction purity of dabigatran ester.Based on the overview and basic synthesis methods of dabigatran ester,improve the synthesis process of dabigatran ester.Determine the optimal reaction conditions through repeated experiments.Experiments have shown that compound 2 can be obtained by alcoholysis at 1.5 eq acetyl chloride,ammonolysis at 20℃,and salt formation of p-toluenesulfonic acid at 3.0 eq.Compound 3 can be obtained by using dichloromethane as the reaction solvent,which can save investment costs,improve reaction yield and extraction purity.

关 键 词：血栓栓塞性疾病 达比加群酯 合成工艺 反应收率 提取纯度 二氯甲烷 

分 类 号：R914.5[医药卫生—药物化学]