Thionyl Chloride → 4-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

HRID 1386258Notes

Reaction equation

HRID 1386258 reaction equation
O[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.S(Cl)([Cl:26])=O>>[Cl:26][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

3

Reactant 2

HCID 24386Thionyl ChlorideHCID 1784867726-methoxy-7-(3-morpholin-4-ylpropoxy)-1H-quinazolin-4-one

Product 1

HCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolineYield 87%

Procedure

A mixture of 4-hydroxy-6-methoxy-7-(3-morpholinopropoxy)quinazoline (638 mg, 2 mmol) and thionyl chloride (8 ml) was heated at reflux for 30 minutes. Excess thionyl chloride was removed by evaporation and by azeotroping with toluene (×2). The residue was suspended in methylene chloride and 10% aqueous solution of sodium hydrogen carbonate was added to the mixture. The organic layer was separated, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether, the solid was collected by filtration, washed with ether and dried under vacuum to give 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (590 mg, 87%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 30 minutes
  3. customExcess thionyl chloride was removed by evaporation
  4. customby azeotroping with toluene (×2)
  5. addition10% aqueous solution of sodium hydrogen carbonate was added to the mixture
  6. customThe organic layer was separated
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. customThe residue was triturated with ether
  10. filtrationthe solid was collected by filtration
  11. washwashed with ether
  12. customdried under vacuum

Sources & evidence

ORD record
ord-637ab674485b4c16aa1783ab67ca896d
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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