反应详情

A solution of 4-bromo-7-(4-hydroxy-2,2-dimethylbutanamido)-9H-carbazole-1-carboxamide (Intermediate 58-1, 89 mg, 0.213 mmol), diethyl azodicarboxylate (0.051 mL, 0.319 mmol) and triphenylphosphine (84 mg, 0.319 mmol) in THF (1 mL) was stirred at rt for 1 h. More diethyl azodicarboxylate (0.051 mL, 0.319 mmol) and triphenylphosphine (84 mg, 0.319 mmol) were added, and these additions repeated again after 1 h more. The mixture was diluted with DCM, washed with NaHCO3 (aq) and water, and dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from DCM to 90:9:1 DCM-methanol-28% aqueous ammonium hydroxide), then by preparative HPLC. The appropriate effluent fractions were made basic with 1 M aqueous sodium hydroxide and extracted twice with DCM. The combined organic phases were washed with water, dried and concentrated to provide 4-bromo-7-(3,3-dimethyl-2-oxopyrrolidin-1-yl)-9H-carbazole-1-carboxamide as a yellow solid (44 mg, 52%). 1H NMR (400 MHz, methanol-d4) δ 8.66 (1 H, d, J=8.58 Hz), 7.94 (1 H, d, J=1.54 Hz), 7.73 (1 H, d, J=8.36 Hz), 7.55 (1 H, dd, J=8.80, 1.98 Hz), 7.39 (1 H, d, J=8.14 Hz), 3.97 (2 H, t, J=6.93 Hz), 2.11 (2 H, t, J=6.93 Hz), 1.28 (6 H, s). Mass spectrum m/z 400, 402 (M+H)+.

1. washwashed with NaHCO3 (aq) and water
2. customdried
3. concentrationconcentrated
4. customThe residue was purified by column chromatography (
5. washeluting with a gradient from DCM to 90:9:1 DCM-methanol-28% aqueous ammonium hydroxide), then by preparative HPLC
6. extractionextracted twice with DCM
7. washThe combined organic phases were washed with water
8. customdried
9. concentrationconcentrated