反应详情

温度

110 °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), palladium acetate (6 mg, 0.025 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (29 mg, 0.05 mmol), oxetan-3-amine (55 mg, 0.75 mmol) and K3PO4 (320 mg, 1.5 mmol) was added toluene (2 mL). The vial was evacuated and flushed with carbon monoxide (2×) and the mixture was heated at 110° C. overnight under an atmosphere of carbon monoxide. The mixture was diluted with DCM/MeOH and concentrated under reduced pressure onto Celite. The residue was purified by silica gel chromatography eluting with 10-100% EtOAc/hexanes to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)-N-(oxetan-3-yl)quinazoline-8-carboxamide (56 mg, 26%). LC-MS (ESI) m/z 421 (M+H)+.

1. customThe vial was evacuated
2. customflushed with carbon monoxide (2×)
3. additionThe mixture was diluted with DCM/MeOH
4. concentrationconcentrated under reduced pressure onto Celite
5. customThe residue was purified by silica gel chromatography
6. washeluting with 10-100% EtOAc/hexanes