N,N-Dimethylaniline → 4-Chloro-6-methoxy-7-(4-pyridylmethoxy)quinazoline

HRID 279519Notes

Reaction equation

HRID 279519 reaction equation
O=P(Cl)(Cl)[Cl:3].[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1)[N:14]=[CH:13][NH:12][C:11]2=O.CN(C)C1C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:3][C:11]1[C:10]2[C:15](=[CH:16][C:17]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)=[C:8]([O:7][CH3:6])[CH:9]=2)[N:14]=[CH:13][N:12]=1

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 135671184HCID 135671184, compound

Product 1

HCID 226249154-Chloro-6-methoxy-7-(4-pyridylmethoxy)quinazolineYield 41%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Phosphorus oxytrichloride (0.1 ml) was added to a mixture of 6-methoxy-7-(4-pyridylmethoxy)-3,4-dihydroquinazolin-4-one (81 mg, 0.29 mmol) and N,N-dimethylaniline (0.1 ml) in toluene (5 ml), and the mixture heated at reflux for 1 hour. The volatiles were removed by evaporation and the residue partitioned between methylene chloride and aqueous ammonia. The organic extract was separated, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by chromatography on silica eluting with ethyl acetate progressing through increasingly polar mixtures to methanol/methylene chloride (1/9) to give 4-chloro-6-methoxy-7-(4-pyridylmethoxy)quinazoline (40 mg, 41%).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 1 hour
  3. customThe volatiles were removed by evaporation
  4. customthe residue partitioned between methylene chloride and aqueous ammonia
  5. extractionThe organic extract
  6. customwas separated
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. customThe residue was purified by chromatography on silica eluting with ethyl acetate progressing
  10. temperaturethrough increasingly polar mixtures to methanol/methylene chloride (1/9)

Sources & evidence

ORD record
ord-53968453313c4e5e8683beb8dcd02ce7
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Reaction notes

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