安立生坦的合成研究

Synthesis of (+)-ambrisentan

以二苯甲酮为原料,经5步反应得到安立生坦,并优化了拆分和取代步骤。在拆分步骤中采用化学性质稳定且便于检测的L-苯甘氨酰胺作为拆分试剂,获得具有较高光学纯度的中间体。在取代反应中采用安全性较高的氢氧化钠作为强碱,适合工业生产。该工艺反应条件温和,操作简便,总收率达到31.0%,具有良好的应用前景。

A five-step synthetic method of ambrisentan starting from benzophenone was developed. The reaction methods of resolution and substitution were optimized. A stable, facilitating method of detection and efficient resolution reagent, L-phenylglycinamide, was used and helped to obtain highly optical pure intermediates. In the substitution reaction, NaOH was chosen as the base, which is safe and suitable for the industry. This method was mild, easily operated with a total yield up to 31. 0%, and may have a good application prospect.