反应详情

温度

100 °C

A mixture of 4-bromo-3-chloro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide [Intermediate 3] (0.360 g, 0.943 mmol), 8-fluoro-3-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)quinazoline-2,4(1H,3H)-dione [Intermediate 17] (0.392 g, 0.990 mmol), PdCl2(dppf) DCM adduct (0.039 g, 0.047 mmol) and Cs2CO3 (0.615 g, 1.89 mmol) in dioxane (10 mL) and water (2.5 mL) was heated at 100° C. overnight. The cooled mixture was diluted with EtOAc and washed with water, dried and concentrated. The residue was purified by column chromatography on silica gel, eluting with EtOAc-hexanes (gradient from 0-50%, then to 70% containing 1% MeOH), to provide 3-chloro-4-(3-(8-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-methylphenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide (mixture of four atropisomers) as a white solid (0.361 g, 67% yield). Mass spectrum m/z 354 (M+H—H2O)+, 394 (M+Na)+. 1H NMR (500 MHz, MeOH-d4) δ 8.09 (d, J=1.1 Hz, 1H), 7.95 (d, J=8.0 Hz, 1H), 7.81-7.69 (m, 1H), 7.64-7.54 (m, 2H), 7.48 (dd, J=7.8, 1.1 Hz, 1H), 7.43-7.29 (m, 1H), 7.31-7.24 (m, 1H), 7.18 (dd, J=8.3, 1.7 Hz, 1H), 7.16-7.07 (m, 1H), 6.92 (dd, J=8.6, 5.3 Hz, 1H), 1.94-1.71 (m, 3H), 1.65-1.50 (m, 6H).

1. washwashed with water
2. customdried
3. concentrationconcentrated
4. customThe residue was purified by column chromatography on silica gel
5. washeluting with EtOAc-hexanes (gradient from 0-50%
6. additionto 70% containing 1% MeOH),