Phosphorus pentachloride → 2-Methylquinazolin-5-amine

HRID 1443215Notes

Reaction equation

HRID 1443215 reaction equation
[CH3:1][C:2]1[NH:11][C:10](=O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[N+:13]([O-])=O)[N:3]=1.P(Cl)(Cl)(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>P(Cl)(Cl)(Cl)=O.[Pd]>[NH2:13][C:8]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:9]=1[CH:10]=[N:11][C:2]([CH3:1])=[N:3]2

Participants

6

Reactant 3

HCID 24819Phosphorus pentachlorideHCID 516892Sodium BicarbonateHCID 136342146HCID 136342146, compound

Product 1

HCID 179850582-Methylquinazolin-5-amineYield 5.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 24813Phosphorus oxychlorideSolvent

Procedure

12.7 g (62 mmol) of 2-methyl-5-nitro-3H-quinazolin-4-one (M. T. Bogert, V. J. Chambers J. Org Chem. 1905, 649-658) and 37.5 g of phosphorus pentachloride are refluxed in 75 ml of phosphoryl chloride over 20 hours. After cooling, it is poured into saturated NaHCO3 solution and extracted with ethyl acetate. The organic phase is dried, and the solvent is removed. 14 g of 4-chloro-2-methyl-5-nitroquinazoline, of which 4.5 g (20.2 mmol) in 225 ml of ethyl acetate and 22.5 ml of triethylamine are dissolved, is obtained. 2 g of palladium on carbon is added, and it is stirred while being cooled with ice for 4 hours under a hydrogen atmosphere at normal pressure. Catalyst is removed from the solution by means of filtration through Celite, whereby it is rewashed with 200 ml of ethanol and concentrated by evaporation. After chromatography on silica gel with ethyl acetate-ethanol (0-10%), 530 mg of the product is obtained.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. customThe organic phase is dried
  4. customthe solvent is removed
  5. dissolution14 g of 4-chloro-2-methyl-5-nitroquinazoline, of which 4.5 g (20.2 mmol) in 225 ml of ethyl acetate and 22.5 ml of triethylamine are dissolved
  6. customis obtained
  7. temperaturewhile being cooled with ice for 4 hours under a hydrogen atmosphere at normal pressure
  8. customCatalyst is removed from the solution by means of filtration through Celite, whereby it
  9. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-f3958abb3e6f455db09c1b214b028f9f
Source dataset
uspto-grants-2010_02
Patent number
US07659297B2

Reaction notes

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