Phosphorus oxychloride → 4,8-Dichloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazoline

Participants

Reaction Conditions

Reaction Steps

To 8-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4(3H)-one (250 mg, 0.77 mmol) were added DIEA (0.28 mL, 1.53 mmol) and phosphorous oxychloride (5.3 mL, 57 mmol), and the mixture was heated at 115° C. for 6 h. The mixture was allowed to cool to rt and was concentrated under reduced pressure. Toluene was added and evaporated twice, and the residue was partitioned between EtOAc (20 mL) and cold saturated aq NaHCO3 (10 mL). The separated EtOAc layer was diluted with EtOAc (60 mL) and washed with saturated aq NaHCO3 (10 mL) and brine (2×10 mL), dried over MgSO4, filtered and concentrated under reduced pressure to afford 4,8-dichloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazoline as a brown viscous oil (294 mg).

Provenance & Evidence