N-bromobutanimide → 2-Bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (283b) (1.44 g, 5.55 mmol) in DCM (13.88 mL) at 0° C. was added TEA (0.91 mL, 6.54 mmol) and tert-butyldimethylsilyl trifluoromethanesulfonate (Sigma-Aldrich) (1.40 mL, 6.11 mmol). The overall mixture was stirred at 0° C. for 1 h, while under inert atmosphere. The reaction mixture was treated with saturated NaHCO3 (20 mL) and the layers were separated. The aq. layer was extracted with DCM (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. m/z (ESI, +ve) 374 (M+H). The residue was treated with THF (13.88 mL) and water (1.6 mL). The resulting mixture was chilled to 0° C. in an ice/water bath. NBS (Alfa Aesar, Ward Hill, Mass.) (0.99 g, 5.55 mmol) was added into the mixture and the overall mixture was stirred at 0° C. for 30 min. The mixture was diluted with DCM (40 mL) and saturated NaHCO3 (10 mL). The layers were separated and the aq. layer was extracted with DCM (3×). The organic extracts were combined, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by chromatography through a SiliCycle SiliaSep pre-packed silica-gel column (120 gram), eluting with a gradient of 0-25% EtOAc in DCM, to provide 2-bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (283c) (1.19 g, 3.52 mmol, 63% yield) as light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.94 (dd, J=9.00, 5.87 Hz, 1H), 7.65-7.84 (m, 1H), 7.32 (t, J=9.39 Hz, 1H), 5.18 (s, 2H), 2.69-2.91 (m, 1H), 2.51 (s, 3H), 0.76-0.95 (m, 2H), 0.60-0.76 (m, 2H). m/z (ESI, +ve) 338/341 (M+H).

Provenance & Evidence