非布索坦的合成工艺研究

Improved Synthetic Process of Febuxostat

摘要:

以4-羟基苯甲腈为合成原料，经硫化、环合、甲酰化、氰化、烷基化、水解反应制得目标产物。改进后的工艺在氰化和烷基化时采用“一锅法”合成，同时考察了硫化反应中盐酸浓度，以及苯环甲酰化反应过程中时间、温度、甲烷磺酸和三氟乙酸比例对产物收率的影响。研究表明，该合成路线操作简单, 反应条件温和，不引入剧毒物质，收率可达到65.7%。

Abstract:

Febuxostat was prepared by 4-hydroxybenzonitrile via sulfuration, cyclization, formylation, cyanation, alkylation and hydrolysis. The cyanation and alkylation reaction were performed by one-pot reaction in improved process, and the key factors, such as concentration of hydrochloric acid, reaction time, temperature, the ratio of methane sulfonic acid to trifluoroacetic acid, were explored. The improved process was convenient, mild reaction condition, and the total yield was as high as 65.7%.