Hydrochloric Acid → N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-2-(phenylamino)nicotinamide

Participants

Reaction Conditions

Reaction Steps

To a brown solution of aniline (0.18 ml, 1.9 mmol) in lithium bis(trimethylsilyl)amide, 1.0 m solution in tetrahydrofuran (1.9 ml, 1.9 mmol) was added 2-fluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)nicotinamide (0.200 g, 0.48 mmol). The mixture was sealed and heated to 70° C. After 2 h, the reaction was cooled to ambient temperature. Water was added, and the pH was adjusted with 6N HCl until slightly acidic. Add to EtOAc/water. Wash the mixture 1× with brine. The organic layer was dried over anhyd. sodium sulfate, filtered, and concentrated to give a brown solid. This material was purified by silica gel chromatography using 90/10 dichloromethane/methanol as eluent to give a yellow solid. Further purification was performed by trituration with dichloromethane and methanol to give N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-2-(phenylamino)nicotinamide as a yellow solid. MS m/z=490 [M+1]+. Calc'd for C28H23N7O2: 489.53.

Provenance & Evidence