维帕他韦关键中间体的合成工艺研究

Improvement on Synthesis of Velpatasvir Intermediate

改进了抗丙肝治疗药维帕他韦关键中间体9-溴-3-(2-溴乙酰基)-10,11-二氢-5H-二苯并[c,g]色烯-8(9H)-酮的合成工艺。以4-溴-3-甲基苯甲酸为起始原料,经取代、环合、溴代得到9-溴-3-(2-溴乙酰基)-10,11-二氢-5H-二苯并[c,g]色烯-8(9H)-酮(1)。关键中间体1的总收率为35%(以4-溴-3-甲基苯甲酸计),其结构经MS、~1H-NMR、^(13)C-NMR确证。该路线所用原料价廉易得、操作简便、条件温和,为工业化生产奠定了基础。

Velpatasvir, a NS5A inhibitor, is effective for the treatment of hepatitis C. An optimal process was developed after summarizing all the synthetic methods reported for velpatasvir intermediate 1. Starting from 4-bromo-3- methylbenzoic acid, 1 was obtained by substitution, cyclization and substitution with the total yield of 35%. Result showed that the structure of Velpatasvir intermediate 1 was confirmed by MS, t H-NMR and 13C-NMR. The improved route had perfect practicality, it also had some advantages such as cheap available material, mild reaction conditions, high yield and simple operation, which was suitable for the large-scale production.