Methanol → HCID 178506148, compound

Participants

Reaction Conditions

Reaction Steps

Charge 4-Chloro-1H-pyrazolo[3,4-d]pyrimidine (93.3 g; 1.00 equiv; 603.66 mmoles; 93.30 g), (4-[4-(3-Trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidine)-, Hydrochloride (1:1) (200.1 g; 1.00 equiv; 603.13 mmoles), and Methanol (1800 mL) to a 5000 mL 4-necked round bottom flask (fitted with nitrogen blanket, rubber septum, mechanical stirrer, heating mantle, condenser and thermocouple probe). Add Triethylamine (280 mL; 2.01 moles) via addition funnel over approximately 15 min. Heat the resulting clear orange solution to 50° C. and hold at 50° C. for 15 min. When reaction is deemed complete by HPLC, add Water (2000 mL) via an addition funnel at 50° C. Add seed crystals during this water addition and the product crystallizes. On completion of addition, heat the slurry to reflux for 1 hour. Cool to room temperature then filter and wash solids with 20% MeOH in water (2×250 mL). Dry the solids in a vacuum oven at 45° C. overnight to afford 4-{4-[4-(3-Trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine as a tan solid (211.5 g, 0.603 mol, 85%).

Provenance & Evidence