Reaction Steps
A solution of benzyl 5-(3-(5-tert-butyl-1-oxoisoindolin-2-yl)-2-methylphenyl)-8-carbamoyl-9H-carbazol-2-ylcarbamate (Example 51-4, 65 mg, 0.102 mmol) in hydrogen bromide (30-35% in acetic acid, 5 mL, 27.6 mmol) was stirred at rt for 1.5 h. The mixture was diluted with DCM and concentrated. The residue was dissolved in DCM containing a small amount of methanol and the solution was mixed with 1 M aqueous sodium hydroxide. The organic phase was separated, washed with water, dried and concentrated, and the residue was triturated with hexane. The residue was purified by column chromatography (eluting with a gradient from 97:2.7:0.3 to 90:9:1 DCM-methanol-28% aqueous ammonium hydroxide) to provide 7-amino-4-(3-(5-tert-butyl-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-carbazole-1-carboxamide as a white solid (Example 54-3, 45 mg, 88%) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 10.32 (1 H, s), 7.89 (1 H, d, J=8.35 Hz), 7.57 (1 H, d, J=7.91 Hz), 7.49-7.55 (2 H, m), 7.35-7.47 (3 H, m), 7.04 (1 H, d, J=7.47 Hz), 6.93 (1 H, d, J=8.35 Hz), 6.74 (1 H, d, J=1.76 Hz), 6.46 (1 H, dd, J=8.57, 1.98 Hz), 4.79 (2 H, d, J=2.20 Hz), 3.84 (2 H, br. s.), 1.96 (3 H, s), 1.40 (9 H, s). Mass spectrum m/z 503.3 (M+H)+. Also obtained was 7-amino-6-bromo-4-(3-(5-tert-butyl-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-carbazole-1-carboxamide as a white solid (Example 54-4, 5 mg, 8%). 1H NMR (400 MHz, chloroform-d) δ 10.34 (1 H, s), 7.89 (1 H, d, J=7.91 Hz), 7.53-7.59 (3 H, m), 7.44-7.48 (2 H, m), 7.35 (1 H, dd, J=5.71, 3.08 Hz), 7.05-7.08 (2 H, m), 6.84 (1 H, s), 4.83 (2 H, s), 4.22 (2 H, br. s.), 1.95 (3 H, s), 1.40 (9 H, s). Mass spectrum m/z 581, 583 (M+H)+.
