Water → 2-Bromo-1-(2-(phenylamino)quinazolin-8-yl)ethanone

Participants

Reaction Conditions

Reaction Steps

NBS (58.2 mg, 0.327 mmol) was added to a solution 8-(1-butoxyvinyl)-N-phenylquinazolin-2-amine (104.5 mg, 0.327 mmol) in THF (2.4 mL) and water (0.094 mL, 5.23 mmol) at 0° C. and the resulting mixture was stirred at 0° C. for 2 min. The mixture was partitioned between Et2O (50 mL) and water (30 mL). The organic layer was separated, sequentially washed with saturated aq. NaHCO3 (20 mL), water (20 mL), and brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo to provide crude 2-bromo-1-(2-(phenylamino)quinazolin-8-yl)ethanone (140 mg) as a yellow-orange oil. NH4OAc (101 mg, 1.309 mmol) and piperidine-2,4-dione (44.4 mg, 0.393 mmol) were added to the resulting oil, and the mixture was taken up in EtOH (2.4 mL) and stirred under argon in a sealed flask at 50° C. for 15.5 h. The reaction was cooled to 25° C. and concentrated in vacuo. The residue was partitioned between DCM (50 mL) and saturated aq. NaHCO3 (30 mL). The aq. layer was extracted with DCM (3×30 mL), and the combined extracts were dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-10% MeOH/DCM) furnished 2-(2-(phenylamino)quinazolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (21.3 mg, 0.060 mmol, 18% yield) as a yellow-orange solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.99 (1H, br. s.), 9.97 (1H, s), 9.35 (1H, s), 8.14 (1H, d, J=7.6 Hz), 7.78 (3H, t, J=7.4 Hz), 7.34-7.45 (4H, m), 7.10 (1H, t, J=7.0 Hz), 7.03-7.07 (1H, m), 3.43 (2H, t, J=6.9 Hz), 2.79 (2H, t, J=6.6 Hz). m/z (ESI, +ve) 356.3 (M+H)+.

Provenance & Evidence