反应详情

Sodium hydride [0.06 g, (60% dispersion in mineral oil)] was added to a solution of cyclobutylmethyl-{1,3-dimethyl-5-[(5-methyl-isoxazol-3-ylamino)-methyl]-1H-pyrazolo[3,4-b]pyridin-6-yl}-ethyl-amine (0.225 g, 0.6 mmol) in anhydrous DMF (3 mL) while stirring at RT. After this mixture was stirred for 1 h, 3,5-bis-trifluoromethybenzyl bromide (0.13 mL, 0.7 mmol) was added slowly and stirring was continued for an additional 12 h. Ethyl acetate (30 mL) and water (30 mL) were added, and the layers were separated. The aqueous layer was back-extracted with ethyl acetate (2×30 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude residue was purified by chromatography using silica gel (200-400 mesh) and eluted with 25-50% hexane:ethyl acetate to yield the title compound as a colorless thick liquid (0.10 g), yield: 29%.

1. stirringAfter this mixture was stirred for 1 h
2. stirringstirring
3. customthe layers were separated
4. extractionThe aqueous layer was back-extracted with ethyl acetate (2×30 mL)
5. washThe combined organic extracts were washed with brine
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated in vacuo
8. customThe crude residue was purified by chromatography
9. washeluted with 25-50% hexane