反应详情

To a suspension of 2-(piperazin-1-yl)propanamide dihydrochloride (0.305 g, 1.33 mmol) in DMSO (1.5 mL), was added 1,1,3,3,-tetramethylguanidine (0.398 g, 3.45 mmol) at rt. The reaction mixture was stirred for 15 min. After that time 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.20 g, 0.664 mmol) was added as a solid in a single portion. The resulting mixture was stirred at 90° C. for 3.5 h. After that time the reaction was cooled to rt and diluted with dichloromethane (50 mL). The organic phase was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 93:7 dichloromethane/methanol) to give 2-(4-(6-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)propanamide (0.080 g, 28%) as a light yellow solid: mp 149-150° C.; 1H NMR (400 MHz, DMSO-d6) δ 11.05 (br s, 1H), 7.65-7.79 (m, 2H), 7.30 (s, 1H), 7.06 (d, J=8.20 Hz, 1H), 6.78 (s, 1H), 6.58 (s, 1H), 4.48 (br s, 1H), 3.91 (s, 3H), 3.86 (s, 3H), 3.64 (br s, 4H), 3.55 (br s, 2H), 2.54 (br s, 4H), 2.45 (t, 2H); ESI MS m/z 439 [M+H]+.

1. stirringThe resulting mixture was stirred at 90° C. for 3.5 h
2. washThe organic phase was washed with brine
3. dry with materialdried over Na2SO4
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by flash column chromatography (silica gel, 93:7 dichloromethane/methanol)