反应详情

A slurry of 8-bromo-2-chloro-3-isopropylquinazolin-4(3H)-one (406c, 0.40 g, 1.326 mmol) and tert-butylamine (4.18 mL, 39.8 mmol) was heated in a sealed tube at 80° C. overnight. The reaction was treated with ice, water, and DCM. The cloudy aq. layer was extracted 4×DCM and 1× EtOAc. The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography (24 g column) using 0-40% EtOAc/hexanes. The product-containing fractions were concentrated to afford 8-bromo-2-(tert-butylamino)-3-isopropylquinazolin-4(3H)-one (0.39 g, 1.15 mmol, 87% yield) as an oil which slowly solidified. 1H NMR (400 MHz, CDCl3) δ ppm 8.05 (1H, dd, J=7.9, 1.5 Hz), 7.83 (1H, dd, J=7.6, 1.4 Hz), 6.97 (1H, t, J=7.7 Hz), 5.55 (1H, br. s.), 4.68 (1H, br. s.), 1.63 (9H, s), 1.55 (6H, d, J=7.2 Hz). m/z (ESI, +ve) 338.0/340.0 (M+H)+.

1. extractionThe cloudy aq. layer was extracted 4×DCM and 1× EtOAc
2. dry with materialThe combined organics were dried over anhydrous Na2SO4
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. additionThe material was treated with DCM
6. custompurified by silica gel chromatography (24 g column)
7. concentrationThe product-containing fractions were concentrated