伐瑞拉迪合成工艺改进

Improved synthesis of varespladib

以4-苄氧基吲哚(2)为原料,经苯磺酰基保护后,在吲哚2位引入乙酰基,经四氢锂铝和三乙基硅氢两步还原将乙酰基还原为乙基,得4-苄氧基-2-乙基-1H-吲哚(6),再引入N-苄基,4位脱苄后,用溴乙酸叔丁酯引入乙酸叔丁酯基,吲哚3位经草酰氯酰化后再氨解,最后水解叔丁酯得伐瑞拉迪(1),总收率24.8%,纯度99.5%,其结构经~1H NMR及MS确证。

Varespladib(1),was synthesized from 4-benzyloxy-1 H-indole(2)via acylation with benzenesulfonyl chloride,acetylation,reduction to give 4-benzyloxy-2-ethyl-1 H-indole(6),which was subjected to substitution with benzyl bromide,deprotection,esterification,substitution with oxalyl chloride,ammonolysis and hydrolysis with overall yield of 24.8%and the purity of 99.5%.The target compound was characterized by 1H NMR and MS.