【摘要】 目的改进4 - [4 -(3,4 亚甲二氧基苯基) - 5 (2 - 吡啶基) 1H 咪唑- 2 - 基]苯甲酰胺(SB -4 315 4 2 )的合成工艺。方法关键中间体4 -[4- (3,4 - 亚甲二氧基苯基) - 5 -(2 - 吡啶基) - N 1 -羟基咪唑 -2 -基]苯腈(1)以三氯化肽[Ti(Ⅲ)Cl3 ]还原得到4 -[4 - (3,4 亚甲二氧基苯基) - 5 - (2 -吡啶基) - 1H 咪唑- 2 - 基]苯腈(2 ) ;2在叔丁醇中以氢氧化钾水解将腈基转化为胺酰基得到了SB -4 315 4 2。结果与讨论中间体和终产物经1H- NMR和MS鉴定,均与文献的数据相符。该合成工艺缩短了合成路线、简化了操作、提高了收率和纯度,避免了使用毒性大的亚磷酸三乙酯[P(OEt) 3 ]。更多还原

【Abstract】 Aim To improve the synthetic procedure of the ALK5 inhibitor 4-[4-（3,4-methylene dioxyphenyl）-5-（2-pyridyl）-1H-imidazol-2-yl]benzamide（SB-431542）.Methods The key intermediate 4-[4-（3,4-methylenedioxyphenyl）-5-（2-pyridyl）-N-1-hydroxyl-imidazol-2-yl]benzonitrile（1）was reduced with （Ti（Ⅲ））Cl₃ to give 4-[4-（3,4-methylenedioxyphenyl）-5-（2-pyridyl）-1H-imidazol-2-yl]benzonitrile（2）.The cyano group of compound 2 was converted to amide by hydrolysis with KOH power in t-BuOH to give the SB-431542.Result and conclusion The （）¹H-NMR and MS data of the intermediates and the end product were identical to that in literature.This improved synthetic route is simpler,more efficient and convenient,its additional merits are furnishing more pure product and avoiding the usage of toxic reagent P（OEt）₃.更多还原