Reaction Steps
A solution of tert-butyl 5-(8-carbamoyl-2-(1-methylpiperidin-4-ylcarbamoyl)-2,3,4,9-tetrahydro-1H-carbazol-5-yl)thiazol-2-yl(isopropyl)carbamate (Example 3-111, 35 mg, 0.059 mmol) in DCM (1 mL) and TFA (1 mL) was stirred at rt for 2 h. The solution was concentrated and the residue was partitioned between DCM and 1 M aqueous sodium bicarbonate. The organic phase was concentrated and the residue was purified by preparative HPLC. The appropriate effluent fractions were made basic with 1 M aqueous sodium hydroxide, extracted twice with DCM, and the combined organic phases were washed with water, dried and concentrated to provide 5-(2-(isopropylamino)thiazol-5-yl)-N2-(1-methylpiperidin-4-yl)-2,3,4,9-tetrahydro-1H-carbazole-2,8-dicarboxamide (Example 4-1, 18 mg, 61%) as a white solid. 1H NMR (400 MHz, methanol-d4) δ 7.51 (1H, d, J=7.91 Hz), 6.95 (1H, d, J=7.91 Hz), 6.89 (1H, s), 3.81-3.89 (1H, m), 3.64-3.73 (1H, m), 2.79-3.07 (4H, m), 2.59-2.75 (3H, m), 2.27 (3H, s), 2.09-2.18 (2H, m), 1.97-2.06 (1H, m), 1.84-1.92 (2H, m), 1.70-1.83 (1H, m), 1.48-1.61 (2H, m), 1.27 (6H, d, J=6.15 Hz). Mass spectrum m/z 495.2 (M+H)+. Also obtained was 4-(2-(isopropylamino)thiazol-5-yl)-N7-(1-methylpiperidin-4-yl)-9H-carbazole-1,7-dicarboxamide as a white solid (Example 4-2, 5.2 mg, 18%). 1H NMR (400 MHz, methanol-d4) δ 8.04-8.10 (2H, m), 7.88-7.93 (1H, m), 7.52-7.58 (1H, m), 7.25 (1H, s), 7.14-7.20 (1H, m), 3.87-3.98 (2H, m), 2.88-2.97 (2H, m), 2.31 (3H, s), 2.15-2.24 (2H, m), 1.95-2.03 (2H, m), 1.64-1.79 (2H, m), 1.32 (6H, d, J=6.59 Hz). Mass spectrum m/z 491.2 (M+H)+.
