【摘要】 目的改进新型抗糖尿病药物GW409544的合成工艺。方法以丙酰乙酸甲酯和L酪氨酸为起始原料,经酯化、胺基保护、溴代、环合、还原、成醚、脱保护、水解、缩合成盐9步反应合成GW409544钙盐(1)。结果与结论合成GW409544钙盐,总产率为9.3%,其结构经核磁(1HNMR)和质谱(MS)确证。改进了中间体2(5-甲基-2-苯基-1,3-噁唑-4-基)乙酸甲酯(7)、(2S)-2-叔丁氧羰基胺基-3-{4-[2-(5-甲基-2-苯基-1,3-噁唑-4-基)乙氧基]苯基}丙酸甲酯(9)的合成工艺。更多还原

【Abstract】 Aim To study the synthesis of GW409544.Methods GW409544 was synthesized by using methyl 3-oxopentanoate and L-tyrosine as the starting material via nine steps,such as esterification,amino protection,bromination,cyclization,reduction,etherification,deprotection,hydrolysis,condensation and salt formation,etc.Results and conclusions The target compound was identified by spectroscopic analysis,and the overall yield was 9.3%.The preparative method of methyl 2-(5-methyl-2-phenyloxazol-4-yl)acetate(7)and(S)-methyl 2-(tert-butoxycarbonylamino)-3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)propanoate(9)are improved.更多还原