Sodium Hydroxide → Nilotinib

Participants

Reaction Conditions

Reaction Steps

To a 1 liter reactor was fed 40 g of 4-methyl-3-(4-(pyridine-3-yl)pyrimidin-2-ylamino)benzoic acid (0.13 mol), 200 ml of N-methylpyrrolidone (NMP) (5V) and 13 ml of thionyl chloride (0.18 mol). The reactor was heated to 60° C. and maintained at 60° C. for 1.5 hr. After 1.5 hr of heating, 31.5 g of 3-(trifluoromethyl)-5-(4-methyl-1H-imidazol-1-yl)benzenamine (0.13 mol) was fed into the reactor. The reactor was then heated to 90° C., and maintained for 30 minutes at this temperature. Then 200 ml (5V) of water was added. The resulting mixture was maintained for 2 hours at 90° C. Then, an additional 240 ml (6V) of N-methylpyrrolidone was added, followed by 26.5 ml of sodium hydroxide (47% aqueous) to raise the pH to 6.5-7. The reactor was then cooled to 40° C. and maintained for 3 hours. The mixture was then filtered and the filter cake was washed with ethanol and water. The washed material was then dried in a vacuum tray oven overnight to provide dry Nilotinib base (62.1 g, Yield 90%)

Provenance & Evidence