A facile total synthesis of imatinib base and its analogues

作者：liu Yi Feng; Wang Cui Ling^*; Bai Ya Jun; Han Ning; Jiao Jun Ping; Qi Xiao Li

来源：Organic Process Research & Development, 2008, 12(3): 490-495.

DOI：10.1021/op700270n

Imatinib and its analogues were successfully synthesized by an improved method in 19.5- 46.2% total yield of six main steps. Pyrimidinyl amine was prepared by the reaction of enaminone and guanidine nitrate without the use of a toxic cyanamide. N-(2-Methyl-5-nitrophenyl)-4-(pyridin-3-yl) pyrimidin-2-amine as a key intermediate for the synthesis of imatinib was prepared by copper-catalyzed N-arylation of heteroarylamine in 82% yield. The copper salts were used instead of the expensive palladium compounds in this C-N bond-forming reaction. The intermediate nitro compound was reduced by a N(2)H(4) center dot H(2)O/FeCl(3)/C system using water as a solvent in good yield.

• 出版日期2008-6
• 单位西北大学; 中国科学院长春应用化学研究所; 上海市精神卫生中心