目的 對安立生坦合成工藝的改進進行研究。方法 以二苯甲酮為起始原料,經(jīng)過縮合、醇解、水解、拆分和取代反應合成安立生坦。醇解采用鹽酸進行反應,采用拆分劑鹽酸鹽和堿試劑通過“一鍋法”進行拆分。結果 優(yōu)化了醇解和拆分反應,避免了高毒性物質的產生;優(yōu)化后,安立生坦的質量分數(shù)為99.7%,光學純度達99.8%,工藝的總收率為30.0%。結論 安立生坦的合成工藝改進后操作性好,條件溫和,避免產生基因毒性和其他高毒性物質,成本較低,更適于藥品的工業(yè)化生產。

Objective To study the improved method for synthesis of ambrisentan. Methods Benzophenone was used as starting material to synthesize the target compound by condensation, alcoholysis, hydrolysis, resolution, and substitution reactions. Hydrochloric acid was used in alcoholysis reaction, and resolving agents hydrochloride and alkali were used in resolution reaction by “one pot” method. Results Alcoholysis and resolution reactions were optimized, avoiding the production of highly toxic substances. After optimization, the purity was 99.7%, and the optical purity was 99.8%. The total recovery of the synthetic route was 30.0%. Conclusion After optimization, the synthetic process of ambrisentan has the advantage of simple operation, mild condition, avoiding gene toxic reagent and other toxic reagent, with low cost, and is suitable for industrial production of drugs.