Dimethylformamide → 2-(Difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline-8-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a mixture of 8-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline (300 mg, 0.75 mmol), tris(dibenzylideneacetone)dipalladium (69 mg, 0.075 mmol), 1,1′-bis(diphenylphosphino)ferrocene (49 mg, 0.088 mmol), and zinc cyanide (110 mg, 0.93 mmol) was added DMF (6 mL). The reaction flask was evacuated and flushed with argon (3×) and then the mixture was heated at 90° C. overnight. The resulting mixture was partitioned between EtOAc and water and the organic layer was washed with 2N NH4OH (3×) and brine (1×), dried over sodium sulfate, and concentrated under reduced pressure onto Celite. The mixture was purified by silica gel flash chromatography eluting with 0-50% EtOAc/hexanes to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline-8-carbonitrile (168 mg, 64%). LC-MS (ESI) m/z 347 (M+H)+.

Provenance & Evidence