A facile total synthesis of imatinib base and its analogues

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 N2H4 center dot H2O/FeCl3/C system using water as a solvent in good yield.