N,N-Dimethylaniline → 4-Chloro-2-(2-methoxy-6-methyl-phenyl)-7-methyl-quinazoline

HRID 2062231Notes

Reaction equation

HRID 2062231 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:4]=1[C:10]1[NH:19][C:18](=O)[C:17]2[C:12](=[CH:13][C:14]([CH3:21])=[CH:15][CH:16]=2)[N:11]=1.CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)[Cl:33].C([O-])(O)=O.[Na+]>C1C=CC=CC=1.C1(C)C=CC=CC=1>[Cl:33][C:18]1[C:17]2[C:12](=[CH:13][C:14]([CH3:21])=[CH:15][CH:16]=2)[N:11]=[C:10]([C:4]2[C:5]([CH3:9])=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[N:19]=1

Participants

7

Reactant 4

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 1361213362-(2-methoxy-6-methyl-phenyl)-7-methyl-3H-quinazolin-4-one

Product 1

HCID 580107904-Chloro-2-(2-methoxy-6-methyl-phenyl)-7-methyl-quinazolineYield 99.1%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 1140TolueneSolvent

Procedure

2-(2-Methoxy-6-methyl-phenyl)-7-methyl-3H-quinazolin-4-one (1.61 g, 5.74 mmol) was suspended in benzene after which was added N,N-dimethylaniline (1.1 mL, 8.62 mmol) and POCl3 (1.61 mL, 17.27 mmol). The reaction mixture was refluxed for 3 hours during which the color changed from yellow to dark red. The reaction mixture was cooled to room temperature, diluted with 40 mL toluene and poured onto ice. Saturated aq. NaHCO3 was carefully added until the pH remained constant at 7 and no more gas formed. The layers were separated, and the water layer was extracted with toluene. The organic layers were combined and washed with respectively 50 mL saturated aq. NaCl, 60 mL 0.5 N HCl, 40 mL 5% NaHCO3 and 50 mL saturated aq. NaCl. The solution was dried over Na2SO4 and evaporated to dryness to yield 1.7 g of the impure product. The product was filtered through silica gel and washed with CH2Cl2:heptane (2:1) to yield of 4-chloro-2-(2-methoxy-6-methyl-phenyl)-7-methyl-quinazoline (1.22 g, 71%).

Workup

  1. temperatureThe reaction mixture was refluxed for 3 hours during which the color
  2. additionpoured onto ice
  3. customno more gas formed
  4. customThe layers were separated
  5. extractionthe water layer was extracted with toluene
  6. washwashed with respectively 50 mL saturated aq. NaCl, 60 mL 0.5 N HCl, 40 mL 5% NaHCO3 and 50 mL saturated aq. NaCl
  7. dry with materialThe solution was dried over Na2SO4
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-cbef6dc98a674e7f9a06e3f4cc47b605
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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