Sodium hydride → 1-Cyclopropyl-6,7-difluoro-8-methoxy-1H-quinazoline-2,4-dione

HRID 729406Notes

Reaction equation

HRID 729406 reaction equation
[CH:1]1([NH:4][C:5]([NH:7][C:8](=[O:20])[C:9]2[CH:14]=[C:13]([F:15])[C:12]([F:16])=[C:11]([O:17][CH3:18])[C:10]=2F)=[O:6])[CH2:3][CH2:2]1.[H-].[Na+].[NH4+].[Cl-]>O1CCCC1.CN(C)C=O>[CH:1]1([N:4]2[C:10]3[C:9](=[CH:14][C:13]([F:15])=[C:12]([F:16])[C:11]=3[O:17][CH3:18])[C:8](=[O:20])[NH:7][C:5]2=[O:6])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 112776651-Cyclopropyl-3-(3-methoxy-2,4,5-trifluorobenzoyl)urea

Product 1

HCID 112656421-Cyclopropyl-6,7-difluoro-8-methoxy-1H-quinazoline-2,4-dione

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-cyclopropyl-3-(3-methoxy-2,4,5-trifluorobenzoyl)urea (Example 27b, 0.94 g, 3.26 mmol) in tetrahydrofuran (20 mL) and N,N-dimethylformamide (5 mL) is treated with sodium hydride (0.275 g, 6.8 mmol, 60% in mineral oil dispersion) and heated at reflux for 16 hours. The mixture is cooled, treated with saturated NH4Cl and extracted with dichloromethane. The organic layer is then washed with brine, dried over Na2SO4 and concentrated under reduced pressure. Flash column chromatography (1:3 ethyl acetate/hexanes) afforded the title compound. MS (EI, M+1) m/z 269.

Workup

  1. temperatureheated
  2. temperatureat reflux for 16 hours
  3. temperatureThe mixture is cooled
  4. extractionextracted with dichloromethane
  5. washThe organic layer is then washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d521ddb5a41e4020997d70d9bfe50003
Source dataset
uspto-grants-2009_09
Patent number
US07582627B2

Reaction notes

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