Sodium hydride → 3-Amino-1-cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dione

HRID 729410Notes

Reaction equation

HRID 729410 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:15])=[C:11]([F:14])[CH:12]=3)[C:7](=[O:16])[NH:6][C:5]2=[O:17])[CH2:3][CH2:2]1.[H-].[Na+].[N+:20](C1C=C([N+]([O-])=O)C=CC=1ON)([O-])=O>O1CCOCC1.CN(C)C=O>[NH2:20][N:6]1[C:7](=[O:16])[C:8]2[C:13](=[CH:12][C:11]([F:14])=[C:10]([F:15])[CH:9]=2)[N:4]([CH:1]2[CH2:3][CH2:2]2)[C:5]1=[O:17]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 87140O-(2,4-dinitrophenyl)hydroxylamineHCID 112764481-Cyclopropyl-6,7-difluoroquinazoline-2,4(1H,3H)-dione

Product 1

HCID 114821773-Amino-1-cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dioneYield 63.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dione (Example 23a, 2.0 g, 8.92 mmol) in dioxane (7.5 mL) and dimethylformamide (7.5 mL) is added NaH (60% dispersion in oil, 428 mg, 10.7 mmol). The solution is heated to 60° C. for 10 minutes and cooled to room temperature. To the cooled solution is added O-(2,4-dinitrophenyl)hydroxylamine (1.77 g, 8.92 mmol), and the solution is heated to 80° C. for 30 minutes. The resulting red solution is cooled to room temperature, poured over crushed ice, and extracted with EtOAc. The combined organic layers are dried over MgSO4, filtered, and the solvent removed under reduced pressure. The resulting solid is triturated with Et2O and air dried to afford 1.44 g of the title compound. MS CI: m/z 254 (MH+).

Workup

  1. temperaturecooled to room temperature
  2. temperaturethe solution is heated to 80° C. for 30 minutes
  3. temperatureThe resulting red solution is cooled to room temperature
  4. additionpoured
  5. customover crushed ice
  6. extractionextracted with EtOAc
  7. dry with materialThe combined organic layers are dried over MgSO4
  8. filtrationfiltered
  9. customthe solvent removed under reduced pressure
  10. customThe resulting solid is triturated with Et2O and air
  11. customdried

Sources & evidence

ORD record
ord-fcf64d84b84f45a1a5f9c9eb388a411f
Source dataset
uspto-grants-2009_09
Patent number
US07582627B2

Reaction notes

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