Thionyl Chloride → 4-Chloro-6-methoxy-7-(2-morpholinoethoxy)quinazoline

HRID 634704Notes

Reaction equation

HRID 634704 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)[N:9]=[CH:8][NH:7][C:6]2=O.S(Cl)([Cl:25])=O>CN(C=O)C>[Cl:25][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 1354968434-Hydroxy-6-methoxy-7-(2-morpholinoethoxy)quinazoline

Product 1

HCID 108710274-Chloro-6-methoxy-7-(2-morpholinoethoxy)quinazolineYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Procedure

A mixture of 6-methoxy-7-(2-morpholinoethoxy)-3,4-dihydroquinazolin-4-one (310 mg, 1.02 mmol), thionyl chloride (10 ml) and DMF (2 drops) was heated at reflux for 4 hours and allowed to cool. Excess thionyl chloride was removed by evaporation and the residue was azeotroped with toluene. The residue was partitioned between aqueous sodium hydrogen carbonate and methylene chloride. The organic layer was separated, washed with brine and filtered through phase separating paper. The volatiles were removed by evaporation and the residue purified by column chromatography eluting with methylene chloridelinethanol (96/4) to give 4-chloro-6-methoxy-7-(2-morpholinoethoxy)quinazoline (225 mg, 68%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 hours
  3. temperatureto cool
  4. customExcess thionyl chloride was removed by evaporation
  5. customthe residue was azeotroped with toluene
  6. customThe residue was partitioned between aqueous sodium hydrogen carbonate and methylene chloride
  7. customThe organic layer was separated
  8. washwashed with brine
  9. filtrationfiltered through phase
  10. customseparating paper
  11. customThe volatiles were removed by evaporation
  12. customthe residue purified by column chromatography
  13. washeluting with methylene chloridelinethanol (96/4)

Sources & evidence

ORD record
ord-62644f81ac8744f2817a6fb1a2f6af75
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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