Sodium hydride → HCID 59375166, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 7-(aminomethyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 33-1, 80 mg, 0.087 mmol) in THF (3 mL) was treated with DIEA (0.030 mL, 0.174 mmol) and a solution of 4-bromobutanoyl chloride (10 μL, 0.087 mmol) in DCM (1 mL) and the mixture was stirred at rt for 35 min. The reaction mixture was diluted with EtOAc, washed with NaHCO3 (aq) and brine, and dried and concentrated. The residue was dissolved in THF (6 mL) and treated with sodium hydride (60% oil dispersion, 24.32 mg, 0.608 mmol). The resulting mixture was stirred at 50° C. for 2 h, then was diluted with water and extracted with EtOAc. The organic phase was dried and concentrated, and the residue was purified by preparative HPLC to provide 4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-7-((2-oxopyrrolidin-1-yl)methyl)-9H-carbazole-1-carboxamide as a white solid (2 mg, 3%). 1H NMR (400 MHz, DMSO-d6) δ 11.44 (1H, s), 8.11 (1H, br. s.), 7.95 (1H, d, J=7.9 Hz), 7.73 (1H, d, J=7.5 Hz), 7.62 (2H, d, J=3.7 Hz), 7.46-7.57 (3H, m), 7.42 (2H, t, J=7.7 Hz), 7.23-7.29 (1H, m), 6.90-6.99 (2H, m), 6.74 (1H, dd, J=8.1, 1.5 Hz), 4.79-5.00 (2H, m), 4.25-4.51 (2H, m), 3.11-3.22 (2H, m), 2.19-2.29 (2H, m), 1.80-1.93 (2H, m), 1.77 (3H, s). Mass spectrum m/z 529.2 (M+H)+.

Provenance & Evidence