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 N 2 H 4 ·H 2 O/FeCl 3 /C system using water as a solvent in good yield.