反应详情

A solution of 3-(tert-butylamino)-5-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxaline-2-carbaldehyde (307b) (44.0 mg, 0.12 mmol), hydroxylamine hydrochloride (11.7 mg, 0.17 mmol), and TEA (0.024 mL, 0.17 mmol) in MeOH (5.0 mL) was stirred at 60° C. for 1.5 h. The reaction mixture was subsequently cooled to RT, diluted with saturated aq. NaHCO3 (20 mL), and extracted with 5% MeOH/DCM (2×30 mL). The combined extracts were sequentially washed with water (30 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated onto silica gel. Chromatographic purification (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) furnished (E)-3-(tert-butylamino)-5-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxaline-2-carbaldehyde oxime (31.0 mg, 0.082 mmol, 68% yield) as an orange solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.34 (1H, br. s.), 11.86 (1H, br. s.), 8.34 (1H, s), 8.31 (1H, s), 7.91 (1H, dd, J=7.3, 1.1 Hz), 7.67 (1H, dd, J=8.0, 1.0 Hz), 7.40 (1H, t, J=7.8 Hz), 7.09 (1H, d, J=2.2 Hz), 6.95 (1H, br. s.), 3.43 (2H, td, J=6.8, 2.2 Hz), 2.86 (2H, t, J=6.8 Hz), 1.57 (9H, s). m/z (ESI, +ve) 379.1 (M+H)+.

1. extractionextracted with 5% MeOH/DCM (2×30 mL)
2. washThe combined extracts were sequentially washed with water (30 mL) and brine (20 mL)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated onto silica gel
6. customChromatographic purification (silica gel, 0-100% EtOAc/hexanes