反应详情

To a solution of 4-(3,4-difluorophenyl)-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-amine (41 mg, 163 μmol) in tetrahydrofurane (1 mL) was added under an atmosphere of nitrogen hexachloroethane (61.0 mg, 245 μmol), triethylamine (49.5 mg, 68.2 μL, 490 μmol) and a 1 M solution of trimethylphosphine in toluene (245 μL, 245 μmol). The suspension was stirred for 30 minutes at room temperature. 1-(6-Methylpyrimidin-4-yl)piperidin-4-one (see example 93b, 46.8 mg, 245 μmol) dissolved in tetrahydrofurane (0.5 mL) was added and the yellow suspension was heated to 150° C. for 30 minutes. A 1 M solution of borane tetrahydrofurane complex in methylene chloride (490 μL, 490 μmol) was added and the reaction was heated to 100° C. for one hour. The reaction was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated. The title compound was obtained as a colorless solid (14 mg, 20%) after column chromatography on silica gel using a gradient from methylene chloride to methylene chloride/methanol 19:1 (v/v) as eluent and subsequent purification with preparative HPCL. MS ISP (m/e): 427.3 (100) [(M+H)+], 176.3 (81).

1. additionwas added
2. temperaturethe yellow suspension was heated to 150° C. for 30 minutes
3. temperaturethe reaction was heated to 100° C. for one hour
4. extractionextracted twice with ethyl acetate
5. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. customthe solvent was evaporated