反应详情

温度

100 °C

To a mixture of 8-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Example 35 step B (336 mg, 0.84 mmol), tris(dibenzylideneacetone)dipalladium (73 mg, 0.08 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (144 mg, 0.25 mmol), morpholin-3-one (102 mg, 1 mmol) and Cs2CO3 (383 mg, 1.18 mmol) was added dioxane (5 mL). The reaction vessel was evacuated and flushed with argon (3×), and the mixture was heated at 100° C. overnight. The mixture was diluted with MeOH and DCM and concentrated under reduced pressure onto Celite. The mixture was purified by silica gel chromatography eluting with 0-100% EtOAc/hexanes to afford 4-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazolin-8-yl)morpholin-3-one (203 mg, 57%) as a mixture which was used without further purification. LC-MS (ESI) m/z 421 (M+H)+.

1. customThe reaction vessel was evacuated
2. customflushed with argon (3×)
3. additionThe mixture was diluted with MeOH and DCM
4. concentrationconcentrated under reduced pressure onto Celite
5. customThe mixture was purified by silica gel chromatography
6. washeluting with 0-100% EtOAc/hexanes