Hydrogen Bromide → Nilotinib hydrobromide

Participants

Reaction Steps

In a 250 mL reactor equipped with a reflux condenser and a mechanical stirrer Nilotinib base Form A (15.00 g, 28.3 mmol) was mixed with acetone (150 mL, 10V). The resulting suspension was heated to reflux over 10 min and stirred at reflux for additional 40 min. To the stirred suspension was added HBr (48% aq, 3.30 mL, 29.2 mmol, 1.03 eq) in one portion. Stirring of the resulting mixture was continued at reflux temperature for 1 h. The mixture was then allowed to cool to room temperature over a period of 3 h and maintained at room temperature overnight. The flask containing the mixture was then transferred to the refrigerator where it was kept for about 3 days at a temperature from 2° C. to about 8° C. (in a closed vessel). The mixture was then filtered and the isolated solid was dried in a vacuum oven (25 mmHg) at 70° C. for 22 h to afford Nilotinib HBr form XI as a yellow solid (17.27 g, 99%). Assay determination confirmed the stoichiometry of the salt as monohydrobromide.

Provenance & Evidence