反应详情

A stirred mixture of 5.0 g of 1-(4-fluorophenyl)-3-(1-piperazinyl)-1H-indazole, 1.6 g of sodium bicarbonate, 1.7 g of chloromethylcyclopropane and 60 ml of dimethylformamide was heated at 85°-90° for 16 hours. Additional chloromethylcyclopropane (0.43 g) was added and the reaction mixture heated at 85°-90° for 8 hrs. The reaction mixture was then poured into water and the aqueous mixture extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate and concentrated to a solid. The solid was purified by flash chromatography on silica gel utilizing ethyl acetate/diethylamine (3%) as the eluent. Concentration of the appropriate fractions gave 3-[4-(cyclopropyl)methyl-1-piperazinyl]-1-(4-fluorophenyl)-1H-indazole as a solid. The solid was dissolved in anhydrous diethyl ether and treated with ethereal hydrogen chloride to give the hydrochloride salt. The salt was recrystallized from ethanol-diethyl ether (twice) to give 2.6 g (40%) of 3-[4-(cyclopropyl)methyl-1-piperazinyl] -1-(4-fluorophenyl)-1H-indazole hydrochloride, mp 213°-215°.

1. temperaturewas heated at 85°-90° for 16 hours
2. temperaturethe reaction mixture heated at 85°-90° for 8 hrs
3. extractionthe aqueous mixture extracted with ethyl acetate
4. washThe extract was washed with water
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated to a solid
7. customThe solid was purified by flash chromatography on silica gel