反应详情

To a solution of 6-[(6-acetylpyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one (Example 10, 0.018 g, 0.042 mmol) in 1 mL of THF at 0° C. was added methylmagnesium bromide (0.035 mL, 3.0 M diethyl ether solution, 0.10 mmol). After 30 min, the mixture was treated with saturated aqueous ammonium chloride and extracted 2× with dichloromethane. The combined organic fractions were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 446.2067 for [M+H]+ [Calc'd for C26H28N3O4, [M+H]+=446.2074]: 1H NMR (400 MHz, CDCl3) δ 8.95-8.93 (m, 1H), 8.40 (s, 1H), 8.29 (s, 1H), 7.85-7.81 (m, 2H), 7.67-7.60 (m, 2H), 7.39 (d, J=8.2 Hz, 1H), 7.18 (d, J=8.2 Hz, 1H), 4.89-4.80 (m, 2H), 4.33 (s, 2H), 4.25-4.04 (m, 3H), 3.60-3.57 (m, 1H), 3.36-3.28 (m, 1H), 2.30-2.15 (m, 1H), 2.02-1.98 (m, 1H), 1.47 (s, 6H).

1. extractionextracted 2× with dichloromethane
2. dry with materialThe combined organic fractions were dried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe residue was purified via silica gel chromatography
6. washeluting with 0-5% methanol in dichloromethane