Thionyl Chloride → 4-Chloro-6-methoxy-7-(2-(4-methylpiperazin-1-yl)ethoxy)quinazoline

HRID 634708Notes

Reaction equation

HRID 634708 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][N:19]([CH3:22])[CH2:18][CH2:17]1)[N:9]=[CH:8][NH:7][C:6]2=O.S(Cl)([Cl:26])=O>CN(C=O)C>[Cl:26][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][N:19]([CH3:22])[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 135509428HCID 135509428, compound

Product 1

HCID 117594994-Chloro-6-methoxy-7-(2-(4-methylpiperazin-1-yl)ethoxy)quinazolineYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Procedure

A mixture of 6-methoxy-7-(2-(4-methylpiperazin-1-yl)ethoxy)-3,4-dihydroquinazolin-4-one (500 mg, 1.57 mmol), thionyl chloride (20 ml) and DMF (3 drops) was heated at reflux for 3 hours and allowed to cool. The excess thionyl chloride was removed by evaporation, and the residue was azeotroped with toluene. The residue was treated with aqueous sodium hydrogen carbonate and the product was extracted with methylene chloride. The combined extracts were washed with brine, passed through phase separating paper and the solvent removed by evaporation to give 4-chloro-6-methoxy-7-(2-(4-methylpiperazin-1-yl)ethoxy)quinazoline (120 mg, 23%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hours
  3. temperatureto cool
  4. customThe excess thionyl chloride was removed by evaporation
  5. customthe residue was azeotroped with toluene
  6. additionThe residue was treated with aqueous sodium hydrogen carbonate
  7. extractionthe product was extracted with methylene chloride
  8. washThe combined extracts were washed with brine
  9. customseparating paper
  10. customthe solvent removed by evaporation

Sources & evidence

ORD record
ord-bd786e9e21684ada878577c23a704115
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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