反应详情

A solution of 8-bromo-2-chloro-3-ethyl-7-fluoroquinazolin-4(3H)-one (512c, 197 mg, 0.645 mmol), tert-butylamine (Aldrich; 1.5 mL, 14.27 mmol), and NMP (0.5 mL) was heated in a sealed microwave vial at 100° C. for 30 min. The reaction mixture was then partitioned between EtOAc (60 mL) and water (40 mL). The organic layer was separated and sequentially washed water (40 mL) and brine (40 mL), then dried over Na2SO4, filtered, and concentrated in vacuo to give as a yellow solid. The combined aqueous layers were subsequently extracted with DCM (2×30 mL), and the combined organic extracts were then sequentially washed with water (2×40 mL) and brine (40 mL), dried over Na2SO4, filtered, and concentrated in vacuo to provide a yellow solid. Combination of the two batches of isolated solids afforded 8-bromo-2-(tert-butylamino)-3-ethyl-7-fluoroquinazolin-4(3H)-one (204.3 mg, 0.597 mmol, 93% yield) as a light-yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.05 (1H, dd, J=8.8, 6.1 Hz), 6.89 (1H, t, J=8.5 Hz), 4.56 (1H, br. s.), 4.05 (2H, q, J=7.2 Hz), 1.62 (9H, s), 1.33 (3H, t, J=7.2 Hz). 19F NMR (376 MHz, CDCl3) δ ppm −96.81 (1F, s). m/z (ESI, +ve) 341.9/343.9 (M+H)+.

1. customThe reaction mixture was then partitioned between EtOAc (60 mL) and water (40 mL)
2. customThe organic layer was separated
3. dry with materialsequentially washed water (40 mL) and brine (40 mL), then dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customto give as a yellow solid
7. extractionThe combined aqueous layers were subsequently extracted with DCM (2×30 mL)
8. washthe combined organic extracts were then sequentially washed with water (2×40 mL) and brine (40 mL)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto provide a yellow solid