反应详情

A stirred solution of 6-chloro-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (16.69 g, 75 mmol), 4-(pyridin-3-yl)piperidin-4-ol (14.70 g, 82.50 mmol) and N-ethyldiisopropylamine (16.98 mL, 97.50 mmol) in DMF (75 mL) was heated at 80° C. for 1 hr. The solution was cooled to ambient temperature and slowly diluted with water, with seeding, giving a crystalline precipitate. The precipitate was collected by filtration, washed with water, acetonitrile and ether and dried under vacuum at 50° C. to afford 4-(pyridin-3-yl)-1-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-ol anhydrous Form A (25.2 g, 92%) as a cream crystalline solid, which was used without further purification. Approximately 30 mg of material was then slurried in approximately 1 ml of ethyl acetate and stirred using a magnetic stirrer bar for 3 days at ambient temperature. The resultant material was air dried and analysed.

1. customgiving a crystalline precipitate
2. filtrationThe precipitate was collected by filtration
3. washwashed with water, acetonitrile and ether
4. customdried under vacuum at 50° C.