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

HRID 473158Notes

Reaction equation

[F:1][C:2]([F:13])([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][N:7]=1)[C:3]([O-])=O.[Na+].[NH2:15][C:16]1[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([NH2:20])=[O:19]>O>[F:1][C:2]([F:13])([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][N:7]=1)[C:3]1[NH:20][C:18](=[O:19])[C:17]2[C:16](=[C:24]([F:25])[CH:23]=[CH:22][CH:21]=2)[N:15]=1

Participants

Conditions

Temperature: 115 °C

Procedure

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)+.

Workup

temperatureto cool to rt
customresulting in a precipitate that
customwas separated
washwashing with DCE (2×8 mL)
washThe combined DCE extracts were washed with brine (3 mL)
customseparated
concentrationThe organic fraction was concentrated

Sources & evidence

ORD record: ord-3163da0a7b0d4d9da8b968971cf8bdde
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08633207B2

Reaction notes

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