反应详情

温度

90 °C

To a mixture of 8-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Example 35 step B (200 mg, 0.5 mmol), tris(dibenzylideneacetone)dipalladium (46 mg, 0.05 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (87 mg, 0.15 mmol), acetamide (89 mg, 1.5 mmol) and Cs2CO3 (230 mg, 0.7 mmol) was added dioxane (4 mL). The reaction vessel was evacuated and flushed with argon (3×), and the mixture was heated at 90° C. overnight. The mixture was diluted with DCM and concentrated under reduced pressure onto Celite. The residue was purified by silica gel chromatography eluting with 0-50% EtOAc/hexanes to afford N-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazolin-8-yl)acetamide (90 mg, 48%). LC-MS (ESI) m/z 379 (M+H)+.

1. customThe reaction vessel was evacuated
2. customflushed with argon (3×)
3. additionThe mixture was diluted with DCM
4. concentrationconcentrated under reduced pressure onto Celite
5. customThe residue was purified by silica gel chromatography
6. washeluting with 0-50% EtOAc/hexanes