反应详情

To a 25 mL round-bottom flask equipped with a magnetic stir bar was added 2-(4-fluoro-2-methyl-phenylamino)-7-(1-hydroxy-allyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (0.65 g, 1.7 mmol), THF (5 mL), triethylamine (0.52 g, 5.1 mmol) and acetic anhydride (0.22 g, 2.2 mmol). To the stirred suspension was then added DMAP (0.002 g, 0.02 mmol). After 1 hour, all reaction components were fully dissolved and the reaction was complete as determined by TLC analysis. To the reaction mixture was added saturated aqueous ammonium chloride (20 mL) and the solution was extracted with ethyl acetate (2×20 mL). The organic fractions were collected, washed with brine (1×20 mL), dried over sodium sulfate, and concentrated in vacuo. The crude product was further purified by silica gel chromatography, eluting with 2% methanol:DCM to provide acetic acid 1-[2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinolin-7-yl]-allyl ester (0.404 g, 55%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6+TFA) δ ppm 11.35 (br s, 1H), 10.55 (br s, 1H), 7.74 (d, 1H, J=9.0 Hz), 7.70 (d, 1H, J=8.6 Hz), 7.56 (dd, 1H, J1=5.5 Hz, J2=8.6 Hz), 7.37-7.34 (m, 3H), 7.25 (td, 1H, J1=2.7 Hz, J2=8.2 Hz), 6.34 (app d, 1H, J=6.3 Hz), 6.17 (ddd, 1H, J1=6.3 Hz, J2=10.2 Hz, J3=16.8 Hz), 5.41 (app d, 1H, J=17.2 Hz), 5.33 (app d, 1H, J=10.2 Hz), 4.18 (s, 3H), 2.32 (s, 3H), 2.12 (s, 3H); ESMS (m/z): found, 435.

1. customTo a 25 mL round-bottom flask equipped with a magnetic stir bar
2. customall reaction components
3. dissolutionwere fully dissolved
4. extractionthe solution was extracted with ethyl acetate (2×20 mL)
5. customThe organic fractions were collected
6. washwashed with brine (1×20 mL)
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated in vacuo
9. customThe crude product was further purified by silica gel chromatography
10. washeluting with 2% methanol