Acetone → 5-(2,6-Dimorpholinopyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-amine hydrochloride hydrate

Participants

Reaction Conditions

Reaction Steps

Charge a nitrogen-flushed 2 L reactor that equipped with an overhead stirrer, condenser, nitrogen inlet/outlet and 500 mL addition funnel with 82.08 g (0.20 mol, 1 eq.) of 5 and 792 g (1.0 L) of acetone. Stir the slurry at 25° C. for 15 minutes. Add a solution of 34.3 mL (0.206 mol, 1.03 eq.) of 6 N hydrogen chloride in water. Add 3 mg of seed. Solids formed. Add 20 mL of water. Heat the batch to reflux (55-56° C.) and maintain at reflux for 15 minutes. Cool to 20° C. over 1.5 h. Cool to 5° C. over 1 h and filter the solids. Wash the filter cake with 80 mL of 5° C. acetone and dry the solids at 40° C., 35 mbar for 16 h to afford 70.4 g (75.7% yield) of the title compound as a yellow, crystalline solid. Following this procedure, the resulting compound is the monohydrate of the monohydrochloride salt (Polymorph Form Ha) of the Compound of Formula A.

Provenance & Evidence