铜催化酰胺和溴代嘧啶胺的碳氮偶联反应

Copper catalyzed coupling reaction of N-(5-bromo-2-methylphenyl)-4-( pyridin-3-yl) pyrimidin-2-amine with aryl amides

用CuI作催化剂,对N-(5-溴-2-甲苯基)-4-(3-吡啶基)-2-嘧啶胺和一些系列酰胺的C-N偶联反应进行了研究。通过条件试验,对适配碱的种类、溶剂、配体以及用量进行了筛选。并选用D-抗坏血酸钠作为抗氧剂,使偶联反应在开放的体系中方便地进行。方法简便,产率较高。采用该方法合成出了靶向抗癌药伊马替尼(格列卫),以及一些具有相似结构的N-嘧啶胺基苯基取代苯甲酰胺类衍生物。

The C-N coupling reaction of N-(5-bromo-2-methylphenyl)-4-(pyridin-3-yl) pyrimidin-2-amine with a series of amides was studied using CuI as catalyst. The types and dosage of adapted alkali,solvents and ligands were screened through conditional tests. D-sodium ascorbate was chosen as antioxidant to facilitate the coupling reaction in an open system. The method is simple and the yield is high. The synthesis of the targeted anticancer drug imatinib( Gleevec),and some N-pyrimidine aminophenyl substituted benzamides derivatives was accomplished by this method.