抗丙肝新药daclatasvir dihydrochloride的合成

Synthesis of the anti-hepatitis drug daclatasvir dihydrochloride

目的:合成抗丙肝新药daclatasvir dihydrochloride,并对其工艺进行改进。方法:以联苯为原料经傅克酰基化,亲核取代,环合,酸化脱保护和亲核取代反应制得daclatasvir dihydrochloride。结果:目标产物结构经1H-NMR和MS确证,整个工艺总收率为23.9%。结论:本路线操作简便、成本较低、条件温和、步骤少,适合工业化生产。

Objective： To synthesize daclatasvir dihydrochloride, an anti-hepatitis C drug, and optimize the preparing process. Methods： Daclatasvir dihydrochloride was prepared by Friedel-Crafts acylation, nucleophil- ic substitution, cyclization, acidification deprotection and nucleophilic substitution reaction using diphenyl as start- ing material. Results： The structure of the target product was verified by 1H-NMR and MS. The total yield was 23.9%. Conclusion： This improved method has the advantages of simpler purifying operation, lower cost, milder conditions and fewer steps. It can be used in industrial manufactrring.