N,N-Dimethylaniline → HCID 58683904, compound

HRID 2406173Notes

Reaction equation

HRID 2406173 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19])[NH:6][C:5]2=O.CN(C)C1C=CC=CC=1.P(Cl)(Cl)([Cl:32])=O.[OH-].[Na+]>C1C=CC=CC=1.ClCCl>[Cl:32][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=2)[N:8]=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[O:18][CH3:19])[N:6]=1

Participants

7

Reactant 4

HCID 949N,N-DimethylanilineHCID 14798Sodium Hydroxide2×HCID 24813Phosphorus oxychlorideHCID 1361214776-fluoro-2-(2-methoxyphenyl)-3H-quinazolin-4-one

Product 1

HCID 58683904HCID 58683904, compoundYield 76.6%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of 6-fluoro-2-(2-methoxyphenyl)-3H-quinazolin-4-one (14.0 g, 52 mmol), N,N-dimethylaniline (6.6 mL, 52 mmol), and phosphorus oxychloride (4.8 mL, 52 mmol) in benzene (100 mL) was heated at reflux until a clear, dark solution was obtained (1 hour). The reaction mixture was cooled to room temperature, and the volume was reduced under reduced pressure. The black, oily residue was poured into 300 g of ice. Dichloromethane (600 mL) was added with vigorous stirring, and the temperature was kept below 5° C. at all times. The pH was monitored, and aqueous 1 N sodium hydroxide was added until the pH was 10-11. The mixture was stirred for one hour at a temperature below 5° C., and the pH was kept between 10-11 by addition of 1 N aqueous sodium hydroxide. The layers were separated, and the organic layer was washed with ice cold 1 N aqueous sodium hydroxide (2×200 mL). Heptanes (300 mL) were added to the organic layer. This mixture was filtered through a short plug of silica gel and eluted with dichloromethane/heptanes (2:1). All fractions containing product were combined and evaporated to dryness. The residue was triturated with heptanes to yield 4-chloro-6-fluoro-2-(2-methoxyphenyl)-quinazoline (11.5 g, 76%) as a white solid.

Workup

  1. temperaturewas heated
  2. temperatureat reflux until a clear, dark solution
  3. customwas obtained (1 hour)
  4. customwas kept below 5° C. at all times
  5. customThe layers were separated
  6. washthe organic layer was washed with ice cold 1 N aqueous sodium hydroxide (2×200 mL)
  7. additionHeptanes (300 mL) were added to the organic layer
  8. filtrationThis mixture was filtered through a short plug of silica gel
  9. washeluted with dichloromethane/heptanes (2:1)
  10. additionAll fractions containing product
  11. customevaporated to dryness
  12. customThe residue was triturated with heptanes

Sources & evidence

ORD record
ord-37ee949dd067436c99f18a28744febc4
Source dataset
uspto-grants-2014_08
Patent number
US08809353B2

Reaction notes

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