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

HRID 729413Notes

Reaction equation

HRID 729413 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.O1CCCC1.[H-].[Na+].[N+:25](C1C=C([N+]([O-])=O)C=CC=1NO)([O-])=O>CN(C)C=O.O1CCOCC1>[NH2:25][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

7

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 5743493N-Hydroxy-2,4-dinitrobenzenamineHCID 112764481-Cyclopropyl-6,7-difluoroquinazoline-2,4(1H,3H)-dione

Product 1

HCID 114821773-Amino-1-cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dione

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of a 1-cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dione (Example 23) in 1:1 dry tetrahydrofuran or dioxane and dry N,N-dimethylformamide is added portionwise sodium hydride (1.1 eq., 60% mineral oil dispersion) at room temperature. After stirring at 50° C. for 20 to 30 minutes, the resulting solution is cooled to room temperature and 2,4-dinitrophenylhydroxylamine (4 eq.) is added. The mixture is heated at 60° C. to 80° C. for 30 minutes, cooled, and the dioxane removed reduced pressure. The residue is poured into ice water and extracted with ethyl acetate. The organic layers are combined, washed with brine, dried with Na2SO4, and concentrated in vacuo. The residue is purified by flash column chromatography (ethyl acetate/hexanes) to afford a 3-amino-1-cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dione.

Workup

  1. temperaturethe resulting solution is cooled to room temperature
  2. temperatureThe mixture is heated at 60° C. to 80° C. for 30 minutes
  3. temperaturecooled
  4. customthe dioxane removed reduced pressure
  5. additionThe residue is poured into ice water
  6. extractionextracted with ethyl acetate
  7. washwashed with brine
  8. dry with materialdried with Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by flash column chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ccea951bb6354f5badc6e51d38a8f76b
Source dataset
uspto-grants-2009_09
Patent number
US07582627B2

Reaction notes

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