Phosphorus oxychloride → 2-Chloro-6,7-dimethoxyquinazoline

HRID 570020Notes

Reaction equation

HRID 570020 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[C:8](O)[N:7]=[CH:6]2.P(Cl)(Cl)([Cl:18])=O>>[Cl:18][C:8]1[N:7]=[CH:6][C:5]2[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178486743HCID 178486743, compound

Product 1

HCID 18181442-Chloro-6,7-dimethoxyquinazolineYield 38%

Procedure

Phosphorus oxychloride (50 ml) was added to 5.0 g of the 6,7-dimethoxy-2-hydroxyquinazoline synthesized in Referential Example 89. They were heated and reacted for 8 hours under reflux. After allowing the reaction mixture to cool down, phosphorus oxychloride was distilled off under reduced pressure and the residue was dissolved in dichloromethane. After washing the dichloromethane solution once with a saturated aqueous solution of sodium bicarbonate, once with water and then once with saturated saline, the solution was dried with anhydrous sodium sulfate. The solvent was distilled under reduced pressure and the residue was purified by column chromatography (silica gel; eluent: 50:1 mixed solvent of dichloromethane and methanol), thereby obtaining 2.1 g of the intended product as crystals (yield: 38%).

Workup

  1. customsynthesized in Referential Example 89
  2. temperatureThey were heated
  3. customreacted for 8 hours
  4. temperatureunder reflux
  5. temperatureto cool down
  6. distillationphosphorus oxychloride was distilled off under reduced pressure
  7. dissolutionthe residue was dissolved in dichloromethane
  8. washAfter washing the dichloromethane solution once with a saturated aqueous solution of sodium bicarbonate
  9. dry with materialonce with water and then once with saturated saline, the solution was dried with anhydrous sodium sulfate
  10. distillationThe solvent was distilled under reduced pressure
  11. customthe residue was purified by column chromatography (silica gel; eluent: 50:1 mixed solvent of dichloromethane and methanol)

Sources & evidence

ORD record
ord-c1252f7ea1b441c19e8713f06e4577de
Source dataset
uspto-grants-1988_03
Patent number
US04734418

Reaction notes

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