Diethyl (ethoxymethylene)malonate → Diethyl[(6-nitro-4-quinazolinylamino)methylene]propanedioate

HRID 2296441Notes

Reaction equation

HRID 2296441 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(O[CH:18]=[C:19]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:20]([O:22][CH2:23][CH3:24])=[O:21])C.[H-].[Na+].[Cl-].[NH4+]>CN(C)C=O.CO>[N+:12]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][N:3]=[C:2]2[NH:1][CH:18]=[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:25]([O:27][CH2:28][CH3:29])=[O:26])([O-:14])=[O:13]

Participants

7

Reactant 4

HCID 6871Diethyl (ethoxymethylene)malonateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 130604546-Nitroquinazolin-4-amine

Product 1

HCID 13060485Diethyl[(6-nitro-4-quinazolinylamino)methylene]propanedioateYield 60.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

A mixture of 4-amino-6-nitroquinazoline (57.0 g) and diethyl ethoxymethylenepropanedioate (130 g) in anhydrous N,N-dimethylformamide (570 ml) was cooled at 5° C. To the reaction mixture was added sodium hydride (65.5% in mineral oil) (13.2 g) in the course of 30 minutes and the mixture was stirred for 1 hour and 40 minutes under ice-cooling. After ammonium chloride (47.2 g) was added to the reaction mixture and stirred for 20 minutes, ice-water (1 liter) was added to the resultant mixture with stirring and allowed to stand to give crystals, which were separated by filtration, washed with water and dried overnight at ambient temperature. The resultant crude crystals were dissolved in chloroform (1.5 liters) under heating. Insoluble materials were filtered off and the filtrate was concentrated under reduced pressure to give crystals, which were dissolved in methanol (300 ml) under heating and allowed to stand at ambient temperature. The resultant crystals were separated by filtration, washed with methanol and dried under reduced pressure to give yellowish crystalline diethyl [(6-nitro-4-quinazolinylamino)methylene]propanedioate (64.9 g).

Workup

  1. temperaturecooling
  2. stirringstirred for 20 minutes
  3. stirringwith stirring
  4. customto give crystals, which
  5. customwere separated by filtration
  6. washwashed with water
  7. customdried overnight at ambient temperature
  8. dissolutionThe resultant crude crystals were dissolved in chloroform (1.5 liters)
  9. temperatureunder heating
  10. filtrationInsoluble materials were filtered off
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customto give crystals, which
  13. temperatureunder heating
  14. customto stand at ambient temperature
  15. customThe resultant crystals were separated by filtration
  16. washwashed with methanol
  17. customdried under reduced pressure

Sources & evidence

ORD record
ord-9b87e4d2b21148da93cac2ea3d128ce7
Source dataset
uspto-grants-1984_01
Patent number
US04429126

Reaction notes

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