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

HRID 1384533Notes

Reaction equation

HRID 1384533 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%). 1H NMR Spectrum: (DMSOd6) 4.04(s, 3H); 5.47(s, 2H); 7.46(s, 1H); 7.50(d, 2H); 7.53(s, 1H); 8.60(d, 2H); 8.85(s, 1H) MS-ESI: 302 [MH]+

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-d851cbb2798b4250b82114a89e1634e4
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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