Phosphorus oxychloride → 2-Chloro-8-isopropyl-7-methoxyquinazoline

HRID 1609797Notes

Reaction equation

HRID 1609797 reaction equation
[CH3:1][O:2][C:3]1[C:12]([CH:13]([CH3:15])[CH3:14])=[C:11]2[C:6]([CH:7]=[N:8][C:9](=O)[NH:10]2)=[CH:5][CH:4]=1.P(Cl)(Cl)([Cl:19])=O>>[Cl:19][C:9]1[N:8]=[CH:7][C:6]2[C:11](=[C:12]([CH:13]([CH3:15])[CH3:14])[C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[N:10]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 222602268-isopropyl-7-methoxyquinazolin-2(1H)-one

Product 1

HCID 222602072-Chloro-8-isopropyl-7-methoxyquinazoline

Conditions

Temperature
110 °C

Procedure

7-Methoxy-8-(2-propyl)quinazol-2(1H)-one (1.2 g) was dissolved in 25 mL of phosphorus oxychloride, and the resulting reaction mixture was heated at 110° C. for 2 hours. Excess POCl3 was removed under reduced pressure. To the residue ice-cold water was added, and the product was extracted with ethyl acetate (3×50 mL). The combined organic extract was washed with brine, dried over anhydrous sodium sulfate, and concentrated to give the title compound. This was purified on a column of silica gel (Hexane:Ethyl acetate), off-white solid, (780 mg, 60%), mp 135–137° C.; 1H NMR (CDCl3): δ 1.41 (d, 6H, 2×CH3), 4.02 (s, 3H, OCH3), 4.33 (m, 1H, CH), 7.38 (d, 1H, Ar-H, J=9 Hz), 7.8 (d, 1H, Ar-H, J=9 Hz), 9.1 (s, 1H, Ar-H).

Workup

  1. customthe resulting reaction mixture
  2. customExcess POCl3 was removed under reduced pressure
  3. additionTo the residue ice-cold water was added
  4. extractionthe product was extracted with ethyl acetate (3×50 mL)
  5. extractionThe combined organic extract
  6. washwas washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-8705d1f3b28745c9b8ca3bb643eb57ad
Source dataset
uspto-grants-2006_01
Patent number
US06982260B1

Reaction notes

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