2-Amino-3-fluorobenzamide → 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-fluoroquinazolin-4(3H)-one

Participants

Reaction Conditions

Reaction Steps

Sodium 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetate from Example 2 Step B (51 mg, 0.24 mmol) and 2-amino-3-fluorobenzamide (31 mg, 0.2 mmol) were combined with polyphosphoric acid (1.0 g) and the mixture was heated at 115° C. for 20 h with vigorous stirring. The mixture was allowed to cool to rt, then water (3 mL) was added, resulting in a precipitate that was separated washing with DCE (2×8 mL). The combined DCE extracts were washed with brine (3 mL) and separated using Biotage Phase Separators. The organic fraction was concentrated using a Savant Speed Vac to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-fluoroquinazolin-4(3H)-one as an off-white solid (60 mg). LCMS (ESI) m/z 310 (M+H)+.

Provenance & Evidence