索非布韦合成工艺优化

Optimization of Synthesis Process of Sofosbuvir

本文优选了一种索非布韦的合成工艺。方法 :以(2R)-2-脱氧-2-氟-2-甲基脲苷的剩余量和双取代杂质为指标,选择四氢呋喃的用量、格式试剂的用量、N-[(S)-(2,3,4,5,6五氟苯氧基)苯氧基磷酰基]-L-丙氨酸异丙酯的用量为考察因素优选索菲布韦的合成工艺。结果 :确定了反应的最佳投料比。结论 :优选的合成工艺,其反应条件温和、原料易得、操作方便,具有收率高、副反应少、适合工业化生产等特点。

Objective:Optimize the synthesis process of sofosbuvir.Method:With the amount of2’-deoxy-2’-fluoro-2’-C-methyluridineand disubstituted impurity as index,the amount of tetrahydrofuran,format reagent and N-[(S)-(2,3,4,5,6-pentafluorophenoxy)phenoxyphosphinyl]-L-alanine1-Methylethyl ester were selected as factors to optimize the synthesis process of sofosbuvir.Result:Determine the optimum feed ratio of the reaction.Conclusion:Optimized synthesis process,the reaction conditions are mild,raw materialsare easy to obtain,and it is easy to operate,with high yield,less side effects and suitable for industrial production.