目的 對(duì)達(dá)比加群酯的合成工藝進(jìn)行研究.方法 以3-[[[2-[[(4-氰基苯基)氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基](吡啶-2-基)氨基]丙酸乙酯為起始原料,經(jīng)改進(jìn)后的Pinner反應(yīng)得到脒,再與氯甲酸正己酯反應(yīng)得到達(dá)比加群酯.結(jié)果 合成了目標(biāo)化合物,并利用MS和¹H-NMR確證了結(jié)構(gòu);收率為38.8%,質(zhì)量分?jǐn)?shù)為99.6%.結(jié)論 該合成工藝簡(jiǎn)化了操作,設(shè)計(jì)合理,終產(chǎn)物達(dá)比加群酯收率及純度較高,具備工業(yè)化可行性.

Objective To study the synthetic technology of dabigatran etexilate. Methods 3-[[[2-[[(4-Cyanophenyl)amino]methyl]- 1-methyl-1H-benzimidazol-5-yl]carbonyl] pyridin-2- ylamino]propionic acid ethyl ester was used as starting material to synthesize amidine by Pinner reaction, then to obtain target compound by reacting with hexyl chloroformate. Results The target compound was synthesized and characterized by MS and ¹H-NMR. The yield was 38.8% and the purity was 99.6%. Conclusion The synthetic route of dabigatran etexilate has the advantages of simple operation and reasonable design with high yield and purity, and is suitable for industrial production.