2-Amino-3-chlorobenzamide → 8-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4(3H)-one

HRID 473162Notes

Reaction equation

HRID 473162 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]([Cl:25])=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([NH2:20])=[O:19]>O>[Cl:25][C:24]1[CH:23]=[CH:22][CH:21]=[C:17]2[C:16]=1[N:15]=[C:3]([C:2]([F:13])([F:1])[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][N:7]=1)[NH:20][C:18]2=[O:19]

Participants

4

Reactant 2

HCID 141004282-Amino-3-chlorobenzamideHCID 66609989Sodium 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetate

Product 1

HCID 1363405908-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4(3H)-oneYield 92.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

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-chloro-benzamide (34 mg, 0.20 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 and 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 8-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4(3H)-one as an off-white solid (60 mg). LCMS (ESI) m/z 326 (M+H)+

Workup

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

Sources & evidence

ORD record
ord-4cb58f0eeab045728e2728b8257dc007
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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