反应详情

温度

135 °C

To a mixture of 8-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Example 35 step B (300 mg, 0.75 mmol), bis(tri-tert-butylphosphine)palladium (38 mg, 0.075 mmol), tetraethyltin (0.295 mL, 1.5 mmol), and LiCl (95 mg, 2.25 mmol) was added DMF (15 mL). The reaction vessel was evacuated and flushed with argon (2×). The mixture was then heated in a microwave synthesizer at 135° C. for 30 min. The mixture was partitioned between EtOAc and saturated aq sodium bicarbonate and the organic layer was separated, washed with brine, dried over sodium sulfate, and concentrated under reduced pressure onto Celite. The mixture was purified by silica gel chromatography eluting with 0-10% EtOAc/hexanes to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-ethyl-4-(methylthio)quinazoline (193 mg, 73%) as a white solid. LC-MS (ESI) m/z 350 (M+H)+.

1. customThe reaction vessel was evacuated
2. customflushed with argon (2×)
3. customThe mixture was partitioned between EtOAc and saturated aq sodium bicarbonate
4. customthe organic layer was separated
5. washwashed with brine
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated under reduced pressure onto Celite
8. customThe mixture was purified by silica gel chromatography
9. washeluting with 0-10% EtOAc/hexanes