N-Methylaniline → 2-Chloro-4-(N-methylphenylamino)-6-methoxyquinazoline

HRID 973577Notes

Reaction equation

HRID 973577 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.[CH3:15][NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])(=O)C.[Na+]>O1CCCC1.O>[Cl:1][C:2]1[N:11]=[C:10]([N:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:15])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1

Participants

6

Reactant 3

HCID 7515N-MethylanilineHCID 517045Sodium AcetateHCID 99913972,4-Dichloro-6-methoxyquinazoline

Product 1

HCID 100861382-Chloro-4-(N-methylphenylamino)-6-methoxyquinazolineYield 62.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2,4-dichloro-6-methoxyquinazoline, (38.3 g, 0.19M assuming 100% yield from previous step), N-methylaniline (19.26 g, 0.18M), sodium acetate (16.4 g, 0.2M) in tetrahydrofuran (2 liters) and water (1 liter) was stirred at room temperature for 8 days. Reaction was then concentrated to low volume (about 500 ml) and an oil separated out which solidified. The solid was filtered off and extracted with dichloromethane. Silica gel column chromatography followed by evaporation to dryness gave a residue which was washed with 40-60° petroleum ether (to remove trace impurity) to yield title compound (31.25 g) m.p. 133°-134°.

Workup

  1. customReaction
  2. concentrationwas then concentrated to low volume (about 500 ml)
  3. customan oil separated out which
  4. filtrationThe solid was filtered off
  5. extractionextracted with dichloromethane
  6. customSilica gel column chromatography followed by evaporation to dryness
  7. customgave a residue which
  8. washwas washed with 40-60° petroleum ether (to remove trace impurity)

Sources & evidence

ORD record
ord-d5ca6722ad2d453081011d48c17f0d71
Source dataset
uspto-grants-1991_11
Patent number
US05064833

Reaction notes

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