N,N-Dimethylaniline → 6-Bromo-4-chloro-2-(2-methoxyphenyl)quinazoline

HRID 2079293Notes

Reaction equation

HRID 2079293 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19])[NH:6][C:5]2=O.O=P(Cl)(Cl)[Cl:23].CN(C)C1C=CC=CC=1.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19])[N:6]=[C:5]2[Cl:23]

Participants

8

Reactant 4

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychloride2×HCID 516892Sodium BicarbonateHCID 1361214046-Bromo-2-(2-methoxy-phenyl)-3h-quinazolin-4-one

Product 1

HCID 580109046-Bromo-4-chloro-2-(2-methoxyphenyl)quinazolineYield 44%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-Bromo-2-(2-methoxyphenyl)quinazolin-4(3H)-one (0.31 g, 0.94 mmol), POCl3 (86 μL, 0.94 mmol), and N,N-dimethylaniline (180 μL, 1.4 mmol) were refluxed in dry toluene for 3 h. Additional POCl3 (0.94 mmol) was added, and the reaction was refluxed for one additional hour. The reaction mixture was diluted with EtOAc and water. The aqueous layer was made basic with NaHCO3, and the layers were separated. After the organic phase was washed with water, dried over Na2SO4 and concentrated, purification via silica gel chromatography using 0-50% EtOAc in 1:1 hexanes:CH2Cl2 gave 6-bromo-4-chloro-2-(2-methoxyphenyl)quinazoline as a yellow solid (144 mg, 44%). 1H NMR (400 MHz, CDCl3) d 8.45-8.45 (m, 1H), 8.04-7.99 (m, 2H), 7.82 (dd, J=7.6, 1.7 Hz, 1H), 7.49-7.45 (m, 1H), 7.12-7.08 (m, 1H), 7.06 (d, J=8.4 Hz, 1H), 3.90 (s, 3H) ppm; LC/MS: m/z 350.9 (M+H)+ at 3.56 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. temperaturethe reaction was refluxed for one additional hour
  2. customthe layers were separated
  3. washAfter the organic phase was washed with water
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. custompurification via silica gel chromatography

Sources & evidence

ORD record
ord-8fd06a24b9c5418d910ca06e538d2b08
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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