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

HRID 634749Notes

Reaction equation

HRID 634749 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][S: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][S: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 135404741HCID 135404741, compound

Product 1

HCID 108823464-Chloro-6-methoxy-7-(2-thiomorpholinoethoxy)quinazolineYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-methoxy-7-(2-thiomorpholinoethoxy)-3,4-dihydroquinazolin-4-one (1.5 g, 4.6 mmol), thionyl chloride (25 ml) and DMF (0.2 ml) was heated at reflux for 2 hours. Excess thionyl chloride was removed by evaporation and the residue azeotroped with toluene. The resulting gum was partitioned between aqueous sodium hydrogen carbonate solution and methylene chloride. The organic layer was separated and the aqueous layer extracted with methylene chloride (4×40 ml). The combined extracts were passed through phase separating paper, the solvent removed by evaporation and the residue purified by column chromatography eluting with methylene chloride/methanol (95/5). The purified product was triturated with acetone to give 4-chloro-6-methoxy-7-(2-thiomorpholinoethoxy)quinazoline (400 mg, 25%) as an orange/brown solid.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. customExcess thionyl chloride was removed by evaporation
  4. customthe residue azeotroped with toluene
  5. customThe resulting gum was partitioned between aqueous sodium hydrogen carbonate solution and methylene chloride
  6. customThe organic layer was separated
  7. extractionthe aqueous layer extracted with methylene chloride (4×40 ml)
  8. customseparating paper
  9. customthe solvent removed by evaporation
  10. customthe residue purified by column chromatography
  11. washeluting with methylene chloride/methanol (95/5)
  12. customThe purified product was triturated with acetone

Sources & evidence

ORD record
ord-4b15705462224c19a4a2fb0d1c4dec15
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

Loading…