tert-Butyl methyl ether → Nilotinib L-tartrate

Participants

Reaction Conditions

Reaction Steps

Nilotinib base form A (4.00 g, 7.55 mmol) was mixed with ethanol absolute (40 mL, 10V) in a 250 mL reactor equipped with a mechanical stirrer and a reflux condenser to obtain a suspension. The suspension was heated to 80° C. and stirred at the same temperature for 30 min. To the suspension was added a solution of L-tartaric acid (1.25 g, 8.31 mmol, 1.1 mol eq) in ethanol absolute (10 mL, 2.5V) in one portion. The resulting mixture was stirred at 80° C. for 1 hour. Then the heating source was removed and the mixture was allowed to cool to room temperature. The stirring was continued at ambient temperature over a period of 6 h, during which time the mixture became viscous. To the viscous mixture was added another 80 mL ethanol. The mixture was then transferred to the refrigerator and was kept at about 5° C. for 5 days (in a closed vessel) A yellow precipitate formed and was isolated by vacuum filtration to give Nilotinib L-tartrate form IV as indicated by XRD (wet sample). The obtained Nilotinib L-tartrate form IV was dried in a vacuum oven (35 mmHg) at 60° C. for 16 h. The sample was then analyzed by PXRD using a Bruker X-Ray powder diffractometer model D8 and was found to be Nilotinib L-tartrate form IV (4.7 g).

Provenance & Evidence