Thionyl Chloride → 4-chloro-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline

HRID 454128Notes

Reaction equation

HRID 454128 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][CH2:16][N:17]([CH3:22])[S:18]([CH3:21])(=[O:20])=[O:19])[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][CH2:16][N:17]([CH3:22])[S:18]([CH3:21])(=[O:20])=[O:19])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 1357631136-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazolin-4-one

Product 1

HCID 220306904-chloro-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazolineYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Procedure

6-Methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazolin-4-one (2.24 g, 6.6 mmol) was taken up in thionyl chloride (25 ml) and treated with DMF (5 drops). The resulting solution was then heated at reflux for 1 hour followed by cooling to ambient temperature. The excess thionyl chloride was removed by evaporation followed by azeotroping with toluene (3×). The residue was basified with saturated aqueous sodium hydrogen carbonate solution (to pH8) and extracted twice with ethyl acetate. The organic solution was washed with water, brine, dried (MgSO4) and evaporated to dryness to give 4-chloro-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline (1.90 g, 80%).

Workup

  1. temperatureThe resulting solution was then heated
  2. temperatureat reflux for 1 hour
  3. customThe excess thionyl chloride was removed by evaporation
  4. customby azeotroping with toluene (3×)
  5. extractionextracted twice with ethyl acetate
  6. washThe organic solution was washed with water, brine
  7. dry with materialdried (MgSO4)
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-ac85559824ab47df85d8831f4a744665
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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