Water → HCID 56925083, compound

Participants

Reaction Steps

A solution of 7-amino-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 54-14, 60 mg, 0.134 mmol) in THF (3 mL) was treated with TEA (0.019 mL, 0.134 mmol) and a solution of 4-bromobutanoyl chloride (24.92 mg, 0.134 mmol) in DCM (1 mL). The mixture was stirred at rt for 40 min, then was diluted with DCM, washed with water, dried and concentrated. The residue was dissolved in THF (5 mL) and added to a suspension of sodium hydride (60% oil dispersion, 40 mg, 1.000 mmol, pre-washed with hexane) in THF (5 mL). The mixture was stirred at rt overnight, then was heated at 65° C. for 30 min. The mixture was cooled to rt, poured into water and extracted with EtOAc. The organic phase was dried and concentrated, and the residue was purified by column chromatography (eluting with a gradient from 99:0.9:0.1 to 90:9:1 DCM-methanol-28% aqueous ammonium hydroxide) to provide 4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-7-(2-oxopyrrolidin-1-yl)-9H-carbazole-1-carboxamide (50 mg, 66%) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 10.67 (1H, s), 7.96 (1H, d, J=7.47 Hz), 7.91 (1H, s), 7.74 (1H, d, J=7.91 Hz), 7.62-7.67 (1H, m), 7.52-7.58 (2H, m), 7.45-7.48 (2H, m), 7.38-7.42 (1H, m), 7.22 (1H, dd, J=8.79, 1.76 Hz), 7.11 (2H, d, J=7.91 Hz), 4.86 (2H, s), 3.90-4.02 (2H, m), 2.66 (2H, t, J=8.13 Hz), 2.16-2.25 (2H, m), 1.94 (3H, s). Mass spectrum m/z 515.3 (M+H)+.

Provenance & Evidence