Cesium fluoride → 1-(3-(Cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone

Participants

Reaction Conditions

Reaction Steps

A 150-mL round bottomed flask was charged with 8-bromo-N-cyclopropyl-7-fluoro-3-methylquinoxalin-2-amine (283a) (1.60 g, 5.40 mmol), tributyl(1-ethoxyvinyl)tin (Sigma-Aldrich) (2.74 mL, 8.10 mmol), Pd2dba3 (Strem Chemicals) (0.15 g, 0.16 mmol), Xphos (Strem Chemicals) (0.15 g, 0.32 mmol), Cut (Strem Chemicals) (0.21 g, 1.08 mmol) and cesium fluoride (Sigma-Aldrich) (2.46 g, 16.21 mmol) in dioxane (27.0 mL). The flask was purged with argon for 3 min, placed into a pre-heated (80° C.) bath and stirred 2.5 h while under inert atmosphere. The progress of the reaction was monitored by LCMS, which showed desired material. The mixture was removed from the heat bath and cooled to RT. The mixture was treated with 1 N HCl (20 mL) and stirred at RT 30 min. The mixture was filtered through AW Standard Super-Celt NF (Sigma-Aldrich). The filter cake was washed with EtOAc and water. The aq. layer was extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by chromatography through a SiliCycle SiliaSep HP pre-packed silica-gel column (SiliCycle, Quebec City, Canada; 40 gram), eluting with a gradient of 0-20% EtOAc in DCM, to provide 1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (283b) (1.22 g, 4.72 mmol, 87% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.82 (dd, J=9.00, 6.06 Hz, 1H), 7.51 (dd, J=2.74, 0.39 Hz, 1H), 7.23 (t, J=9.29 Hz, 1H), 2.78-2.97 (m, 1H), 2.76 (s, 3H), 2.46 (s, 3H), 0.70-0.83 (m, 2H), 0.52-0.70 (m, 2H). m/z (ESI, +ve) 260 (M+H).

Provenance & Evidence