N,N-Dimethylaniline → 7-Hydroxy-4-ethoxyquinazoline

HRID 624102Notes

Reaction equation

HRID 624102 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:12])[NH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O.CN(C)[C:20]1C=CC=C[CH:21]=1.[Na]>C(O)C>[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][CH2:20][CH3:21])=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 5360545SodiumHCID 135451644Quinazoline-4,7-diol

Product 1

HCID 1358487477-Hydroxy-4-ethoxyquinazoline

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 7-hydroxyquinazolin-4-one (105 mg, 648 μmol), phosphorous oxychloride (2 ml), and dimethylaniline (85 μl, 671 μmol) was heated at reflux for 15 minutes in an argon atmosphere. The cooled mixture was concentrated under vacuum, and kept in an argon atmosphere to avoid hydrolysis. This residue was dissolved in ethanol (anhydrous, 3 mL), and a solution of sodium (283 mg, 12.34 mmol) in ethanol (3 ml) was added dropwise. The resulting yellow mixture was stirred at room temperature under argon for 2 hours, acidified to pH 6 using NaH2PO4 and extracted with ethyl acetate (3×50 mL). The combined extracts were dried (MgSO4), filtered and concentrated. The white solid (156 mg) was used without further purification.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 15 minutes in an argon atmosphere
  3. concentrationThe cooled mixture was concentrated under vacuum
  4. customhydrolysis
  5. extractionextracted with ethyl acetate (3×50 mL)
  6. dry with materialThe combined extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe white solid (156 mg) was used without further purification

Sources & evidence

ORD record
ord-6c342954c5884443b4181eae43b5efb0
Source dataset
uspto-grants-2016_04
Patent number
US09303026B2

Reaction notes

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