2-Amino-3-bromobenzamide → 8-Bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4-ol

HRID 473154Notes

Reaction equation

HRID 473154 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]([Br:25])=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([NH2:20])=[O:19]>>[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]([Br:25])[CH:23]=[CH:22][CH:21]=2)[N:15]=1

Participants

3

Reactant 2

HCID 229310922-Amino-3-bromobenzamideHCID 66609989Sodium 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetate

Product 1

HCID 1363405888-Bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4-olYield 27%

Conditions

Temperature
115 °C

Procedure

Sodium 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetate from Example 2 Step B (0.49 g, 2.3 mmol) and 2-amino-3-bromobenzamide (0.42 g, 1.9 mmol) were combined in trimethylsilylpolyphosphate (4.3 mL) at rt and the mixture was heated at 115° C. for 20 h with vigorous stirring. The mixture was allowed to cool to rt and then was partitioned between water (15 mL) and ethyl acetate (15 mL). The organic layer was separated and the aqueous layer (pH˜1) was extracted with ethyl acetate (3×30 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a 1:10 to 1:1 EtOAc/hexanes to afford 2-[difluoro-(5-fluoro-pyridin-2-yl)-methyl]-8-bromo-3H-quinazolin-4-one as an off-white solid (0.19 g, 22%).

Workup

  1. customwere combined in trimethylsilylpolyphosphate (4.3 mL) at rt
  2. temperatureto cool to rt
  3. customwas partitioned between water (15 mL) and ethyl acetate (15 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer (pH˜1) was extracted with ethyl acetate (3×30 mL)
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with a 1:10 to 1:1 EtOAc/hexanes

Sources & evidence

ORD record
ord-80432f773b9243a1a4a5fb8a1a6b0bcf
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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