phenyl N-(1,3-thiazol-2-yl)carbamate → (R)-7-(4-methylpiperazine-1-carbonyl)-4-(3-(3-thiazol-2-ylureido)piperidin-1-yl)-9H-carbazole-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of (R)-4-(3-aminopiperidin-1-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide (Example 17-1, 23 mg, 0.053 mmol) and TEA (0.015 mL, 0.106 mmol) in THF (3 mL) was treated with phenyl thiazol-2-ylcarbamate (17.49 mg, 0.079 mmol). The mixture was stirred at 60° C. for 1.5 h, then at 70° C. for 2 h, then was concentrated and purified by preparative HPLC. The isolated TFA salt was partitioned between DCM and NaHCO3 (aq), and the organic phase was dried and concentrated to provide (R)-7-(4-methylpiperazine-1-carbonyl)-4-(3-(3-thiazol-2-ylureido)piperidin-1-yl)-9H-carbazole-1-carboxamide as a white solid (14 mg, 43%). 1H NMR (400 MHz, methanol-d4) δ 8.27 (1H, d, J=7.9 Hz), 7.87 (1H, d, J=8.3 Hz), 7.68 (1H, d, J=1.1 Hz), 7.28 (1H, d, J=7.9 Hz), 7.18 (1H, br. s.), 6.93 (1H, d, J=3.7 Hz), 6.87 (1H, d, J=8.3 Hz), 4.25 (1H, br.), 3.82 (2H, br.), 3.41-3.68 (3H, m), 3.19 (3H, br.), 2.36-2.63 (4H, m), 2.33 (3H, s), 1.84-2.20 (3H, m), 1.71 (1H, br. s.). Mass spectrum m/z 561.3 (M+H)+.

Provenance & Evidence