(Z)-2-(2-三苯甲基氨基噻唑-4-基)-2-[1,5-二(二苯甲氧基)-4-吡啶酮-2-基甲氧基亚胺]乙酸的合成工艺改进

Process Improvement on the Synthesis of( Z)-2-( 2-tritylaminothiazol-4-yl)-2-( 1,5-dibenzhydryloxy-4-pyridon-2-ylmethoxyimino) acetic Acid

以5-羟基-2-羟甲基-4-吡喃酮为原料,经羟基保护、迈克尔加成、亲核取代、Mitsunobu反应、肼解及缩合等反应合成了BAL30072关键中间体——(Z)-2-(2-三苯甲基氨基噻唑-4-基)-2-(1,5-二(二苯甲氧基)-4-吡啶酮-2-基甲氧基亚胺)乙酸,总收率23%,其结构经1H NMR和MS确证。该合成工艺已放大到公斤级规模。

The key intermediate of BAL30072,( Z)-2-( 2-tritylaminothiazol-4-yl)-2-[( 1,5-dibenzhydryloxy)-4-pyridon-2-ylmethoxyimino]acetic acid with overall yield of 23%,was synthesized by protection of phenolic hydroxyl group,Michael addition,nucleophilic substitution,Mitsunobu reaction,hydrazinolysis,condensation reaction and so on,using kojic acid as the starting material. The structure was confirmed by1 H NMR and MS.