反应详情

A solution of 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5,8-dichloro-7-(3,5-dimethyl-1,2-oxazol-4-yl)-3,4-dihydroisoquinolin-1(2H)-one (253h, 400 mg, 0.75 mmol) in trifluoroacetic acid (10 mL) was stirred at 45° C. for 3 hours, then concentrated under vacuum to remove volatiles. The residue was partitioned between dichloromethane (15 mL) and saturated aqueous sodium bicarbonate solution (4×20 mL). The organic layer was washed with saturated aqueous sodium chloride solution (20 mL), dried over sodium sulfate, concentrated, and purified by silica gel chromatography (eluting with 10:1 dichloromethane/methanol) to give 5,8-dichloro-7-(3,5-dimethyl-1,2-oxazol-4-yl)-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one (Example 253, 250 mg, 75% yield) as a white solid. 1H NMR (600 MHz, DMSO-17 mm) δ 11.57 (s, 1H), 7.67 (s, 1H), 5.89 (s, 1H), 4.57 (s, 2H), 3.51 (t, J=6.33 Hz, 2H), 2.95 (t, J=6.33 Hz, 2H), 2.24 (s, 3H), 2.18 (s, 3H), 2.12 (s, 3H), 2.06 (s, 3H). MS: 446 [M+1].

1. concentrationconcentrated under vacuum
2. customto remove volatiles
3. customThe residue was partitioned between dichloromethane (15 mL) and saturated aqueous sodium bicarbonate solution (4×20 mL)
4. washThe organic layer was washed with saturated aqueous sodium chloride solution (20 mL)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated
7. custompurified by silica gel chromatography (eluting with 10:1 dichloromethane/methanol)