反应详情

温度

-78 °C

3-[1-(3-Benzyloxy-phenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]-cyclobutanone (100 mg, 248 mols) was dissolved in dry THF (1.0 mL) under inert atmosphere and cooled to −78° C. A solution of MeMgBr (40 μL, 322 mols) in toluene: THF (75:25) was added slowly to the cooled solution. After 24 h of reaction at rt the reaction was cooled to 0° C. and quenched with NH4Cl sat. aq. solution and the aqueous layer was washed with EtOAc (2×). The organic layers where combined, dried over sodium sulfate, filtered and concentrated in vacuo. The crude oil was purified by silica gel column chromatography [Jones Flashmaster, 10 g/70 mL cartridge, eluting with 2-5% ((7N NH3) in MeOH):CH2Cl2], yielding 3-[1-(3-Benzyloxy-phenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]-1-methyl-cyclobutanol as a brown solid.

1. customAfter 24 h of reaction at rt the reaction
2. temperaturewas cooled to 0° C.
3. customquenched with NH4Cl sat. aq. solution
4. washthe aqueous layer was washed with EtOAc (2×)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude oil was purified by silica gel column chromatography [Jones Flashmaster, 10 g/70 mL cartridge, eluting with 2-5% ((7N NH3) in MeOH):CH2Cl2]