反应详情

温度

0 °C

In a microwave vial charge 4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidine dihydrochloride salt (0.5 g, 1.0 eq), 1-(4,6-dichloro-pyrimidin-5-yl)-ethanone (0.22 g, 1.0 eq), TEA (1.2 mL, 8.0 eq) and isopropyl alcohol (5 mL). Stirr the reaction mass at 80° C. for 45 min in microwave. Monitor the reaction by TLC (10% MeOH in DCM). Cool the reaction mass to 0° C. and add hydrazine hydrate (0.07 mL, 1.2 eq). Slowly bring the reaction mass to RT. Stirr the reaction mass at 80° C. for 45 min in microwave. Monitor the reaction by TLC (10% MeOH in DCM). Concentrate the reaction mass under vacuum. Charge ethyl acetate and then wash with water and saturated aq. sodium chloride. Dry the organic layer over anhydrous Na2SO4 and concentrate it under reduced pressure. Purify the compound by column chromatography (Silica gel 60-120 mesh, DCM-Methanol). Crystallize the product in diethyl ether and filter it to give 4-(4-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazol-2-yl)piperidin-1-yl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidine (0.254 g, 50.29%). MS (M+H): m/z=460.5

1. customto RT
2. customat 80° C.
3. customfor 45 min
4. concentrationConcentrate the reaction mass under vacuum
5. washCharge ethyl acetate and then wash with water and saturated aq. sodium chloride
6. dry with materialDry the organic layer over anhydrous Na2SO4
7. concentrationconcentrate it under reduced pressure
8. customPurify the compound by column chromatography (Silica gel 60-120 mesh, DCM-Methanol)
9. customCrystallize the product in diethyl ether
10. filtrationfilter it