4-Fluorobenzoyl chloride → HCID 59375025, compound

Participants

Reaction Steps

A solution of 4-(1H-indol-4-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide (Example 3-47, 50 mg, 0.100 mmol) in DCM (1 mL) was treated sequentially with DMAP (3.7 mg, 0.030 mmol), TEA (0.028 mL, 0.199 mmol) and 4-fluorobenzoyl chloride (0.013 mL, 0.110 mmol). The mixture was stirred at rt for 17 h, then was treated with additional 4-fluorobenzoyl chloride (0.013 mL, 0.110 mmol) and TEA (0.028 mL, 0.199 mmol) and stirring was continued for 111 h. The mixture was concentrated and the residue was dissolved in methanol and purified by preparative HPLC. The appropriate effluent fractions were partitioned between NaHCO3 (aq) and EtOAc, and the aqueous phase was extracted twice more with EtOAc. The combined organic phases were dried and concentrated to provide 4-(1-(4-fluorobenzoyl)-1H-indol-4-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide as a yellow solid (19.5 mg, 31%). 1H NMR (400 MHz, methanol-d4) δ 8.51 (1H, d, J=8.3 Hz), 8.03 (1H, d, J=7.9 Hz), 7.84 (2H, dd, J=8.8, 5.3 Hz), 7.68 (1H, s), 7.57 (1H, t, J=7.7 Hz), 7.46 (1H, d, J=7.5 Hz), 7.26-7.36 (3H, m), 7.20 (1H, d, J=7.9 Hz), 6.96 (1H, d, J=7.9 Hz), 6.86 (1H, dd, J=8.3, 1.3 Hz), 6.19 (1H, d, J=4.0 Hz), 3.77 (2H, br. s.), 3.46 (2H, br. s.), 2.51 (2H, br. s.), 2.38 (2H, br. s.), 2.30 (3H, s). Mass spectrum m/z 574.3 (M+H)+.

Provenance & Evidence