反应详情

温度

100 °C

A glass microwave reaction vessel was charged with 8-bromo-2-chloro-3-cyclopropylquinazolin-4(3H)-one (723) (200 mg, 0.67 mmol), 1-methylcyclopropanamine hydrochloride (Small Molecules, Inc.; 126 mg, 1.17 mmol) and NEt3 (0.46 mL, 3.34 mmol) in DMSO (0.5 mL). The tube was sealed and heated in an oil bath at 100° C. After 1 h, water and EtOAc were added and the layers were separated. The aqueous layer was extracted with EtOAc (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by silica gel chromatography (0-50% EtOAc in hexanes), to provide 8-bromo-3-cyclopropyl-2-((1-methylcyclopropyl)amino)-quinazolin-4(3H)-one (492a) (170 mg, 0.51 mmol, 76% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.02 (dd, J=8.02, 1.56 Hz, 1H), 7.84 (dd, J=7.63, 1.57 Hz, 1H), 6.96 (t, J=7.73 Hz, 1H), 5.77 (s, 1H), 2.65 (tt, J=6.75, 4.11 Hz, 1H), 1.61 (s, 3H), 1.27-1.34 (m, 2H), 0.85-0.92 (m, 4H), 0.80-0.85 (m, 2H). m/z (ES, +ve) 334.0, 336.0 (M+H)+.

1. customA glass microwave reaction vessel
2. customThe tube was sealed
3. customthe layers were separated
4. extractionThe aqueous layer was extracted with EtOAc (2×)
5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude material was absorbed onto a plug of silica gel
9. custompurified by silica gel chromatography (0-50% EtOAc in hexanes)