反应详情

温度

85 °C

A mixture of 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.202 g, 0.67 mmol), 2-(piperazin-1-yl)propan-1-ol dihydrochloride (0.292 g, 1.34 mmol) and 1,1,3,3-tetramethylguanidine (0.310 g, 2.69 mmol) in dry DMSO (1.5 mL) was heated at 85° C. for 6 h. After that time the reaction was cooled to rt, diluted with water (15 mL) and extracted with ethyl acetate (2×30 mL). The combined organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 97:3 dichloromethane/methanol to 95:5 dichloromethane/methanol) to give 2-(6-(4-(1-hydroxypropan-2-yl)piperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.155 g, 54%) as a yellow solid: mp 202-204° C.; 1H NMR (400 MHz, CDCl3) δ 10.30 (s, 1H), 7.87 (d, J=7.42 Hz, 1H), 7.64-7.72 (m, 1H), 6.79-6.88 (m, 2H) 6.49 (d, J=2.34 Hz, 1H) 3.99 (s, 3H), 3.94 (s, 3H), 3.61-3.72 (m, 4H), 3.38-3.52 (m, 2H), 2.89-2.99 (m, 1H), 2.78-2.88 (m, 2H), 2.54-2.64 (m, 2H), 0.97 (d, J=6.64 Hz, 3H); ESI MS m/z 426 [M+H]+.

1. temperatureAfter that time the reaction was cooled to rt
2. extractionextracted with ethyl acetate (2×30 mL)
3. washThe combined organic phase was washed with brine
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe product was purified by flash column chromatography (silica gel, 97:3 dichloromethane/methanol to 95:5 dichloromethane/methanol)