反应详情

A mixture of 2-(4-(4-aminopiperidin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one (0.105 g, 0.28 mmol), methanesulfonylchloride (0.035 g, 0.30 mmol), and Et3N (0.057 g. 0.56 mmol) in CH2Cl2 (10 mL) was stirred at room temperature under nitrogen for 2 hours. The mixture was concentrated, redissolved in THF (5 mL), 2 M NaOH (5 mL) added and stirred for 20 minutes. The pH was adjusted to 8 with 1 M HCl and the mixture extracted with CH2Cl2 (3×150 mL). The organic phase was dried over anhydrous MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography, eluting with 1:1 CH2Cl2/(92:7:1 CHCl3/MeOH/concentrated NH4OH) to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH. Further purification by reverse-phase HPLC. eluting with 10% to 90% CH3CN in H2O with 0.1% TFA. afforded the title compound as a yellow solid (0.075 g, 58%). 1H NMR (300 MHz, DMSO-d6): δ11.75 (s, 1H), 8.08 (d, J=9.0 Hz, 2H), 7.13 (d, J=7.3 Hz, 1H), 7.00 (d, J=9.0 Hz, 2H), 6.66 (d, J=2.3 Hz, 1H), 6.46 (d, J=2.3 Hz, 1H), 3.81-3.94 (m, 8H), 3.34-3.47 (m, 1H), 2.90 (m, 6H), 1.87-1.95 (m, 2H), 1.42-1.54 (m, 2H); ESI MS m/z 459 [M+H]+.

1. concentrationThe mixture was concentrated
2. dissolutionredissolved in THF (5 mL)
3. addition2 M NaOH (5 mL) added
4. stirringstirred for 20 minutes
5. extractionthe mixture extracted with CH2Cl2 (3×150 mL)
6. dry with materialThe organic phase was dried over anhydrous MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by silica gel chromatography
10. washeluting with 1:1 CH2Cl2/(92:7:1 CHCl3/MeOH/concentrated NH4OH) to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH
11. customFurther purification by reverse-phase HPLC
12. washeluting with 10% to 90% CH3CN in H2O with 0.1% TFA