目的 对达比加群酯的合成工艺进行研究.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]丙酸乙酯为起始原料,经改进后的Pinner反应得到脒,再与氯甲酸正己酯反应得到达比加群酯.结果 合成了目标化合物,并利用MS和¹H-NMR确证了结构;收率为38.8%,质量分数为99.6%.结论 该合成工艺简化了操作,设计合理,终产物达比加群酯收率及纯度较高,具备工业化可行性.

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.