反应详情

8-Bromo-2-(tert-butylamino)-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one (461a, 288 mg, 85%) as a brown foam was prepared according to the procedures described for Intermediate 405a, starting from 8-bromo-2-chloro-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one (721) (305 mg, 0.96 mmol). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.90 (1H, dd, J=8.7, 6.4 Hz), 7.04 (1H, t, J=8.7 Hz), 6.25 (1H, s), 2.76-2.88 (1H, m), 1.57 (9H, s), 1.18-1.27 (2H, m), 0.69-0.81 (2H, m). m/z (ESI, +ve ion) 354.0/356.0 (M+H)+. (R)-2-(tert-butylamino)-3-cyclopropyl-7-fluoro-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-one (461) (171 mg, 51%) as a white solid was prepared according to the procedures described for Example 407, starting from 8-bromo-2-(tert-butylamino)-3-cyclopropyl-7-fluoroquinazolin-4(3H)-one (461a, 288 mg, 0.81 mmol). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.79 (1H, s), 7.90 (1H, dd, J=8.8, 6.5 Hz), 7.59 (1H, s), 7.04 (1H, dd, J=10.1, 8.9 Hz), 6.35 (1H, t, J=1.8 Hz), 6.15 (1H, s), 4.49 (1H, q, J=6.5 Hz), 2.76-2.88 (1H, m), 1.40 (9H, s), 1.34 (3H, d, J=6.5 Hz), 1.19-1.28 (2H, m), 0.70-0.78 (2H, m). 19F NMR (377 MHz, DMSO-d6) δ ppm −105.25 (s). m/z (ESI, +ve ion) 410.1 (M+H)+.