摘要
安立生坦是内皮素受体拮抗剂(ERA),用于治疗肺动脉高压(PAH)。以二苯甲酮为原料,经Darzens反应,醇解,水解反应得到2-羟基-3-甲氧基-3,3-二苯基丙酸,然后经非对映体拆分得到(S)-2-羟基-3-甲氧基-3,3-二苯基丙酸,再与4,6-二甲基-2-甲磺酰基嘧啶亲核取代得到安立生坦,总收率30%。该合成工艺反应条件温和、操作简易、收率稳定,具有较好的应用价值。
Ambrisentan is an endothelin-receptor antagonist（ERA）used for the treatment of pulmonary ar-terial hypertension（PAH）. For the preparation of ambrisentan,benzophenone was used as the starting ma-terial. By a series of reactions,such as Darzens condensation,methanolysis and hydrolysis to give 2-hy-droxy-3-methoxy-3,3-diphenylpropionic acid. The latter was subkected to resolution to give（S）-2-hydroxy-3-methoxy-3,3-diphenylpropionic acid. Finally,it reacted with 4,6-dimethyl-2-methylsulfonyl pyrimidine via a nucleophilic substitution to give ambrisentan. The overall yield of the title compound was 30% from benzophenone. This synthesis reaction conditions mild,easy to operate and yield stable with good value.
出处
《应用化工》
CAS
CSCD
2014年第9期1675-1678,共4页
Applied Chemical Industry
关键词
安立生坦
抗肺动脉高血压
内皮素受体拮抗剂
合成
ambrisentan
anti-pulmonary hypertension
endothelin receptor antagonists
synthesis
