Toluene → 4-Chloro-6-methoxy-7-(2-(1,2,4-triazol-1-yl)ethoxy)quinazoline

HRID 1384690Notes

Reaction equation

HRID 1384690 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[CH:20]=[N:19][CH:18]=[N:17]1)[N:9]=[CH:8][NH:7][C:6]2=O.CN(C=O)C.C1(C)C=CC=CC=1.S(Cl)([Cl:36])=O>>[Cl:36][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][N:16]3[CH:20]=[N:19][CH:18]=[N:17]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

5

Reactant 4

HCID 1140TolueneHCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 1356711756-Methoxy-7-(2-(1,2,4-triazol-1-yl)ethoxy)-3,4-dihydroquinazolin-4-one

Product 1

HCID 226248964-Chloro-6-methoxy-7-(2-(1,2,4-triazol-1-yl)ethoxy)quinazolineYield 65%

Procedure

A solution of 6-methoxy-7-(2-(1,2,4-triazol-1-yl)ethoxy)-3,4-dihydroquinazolin-4-one (1.11 g, 3.86 mmol) and DMF (0.6 ml) in thionyl chloride (15 ml) was heated at reflux for 1 hour. The mixture was allowed to cool, toluene was added and the volatiles were removed by evaporation. The residue was partitioned between methylene chloride and water and the aqueous layer was adjusted to pH8.5 with saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated, washed with brine, dried (MgSO4), and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5). The purified solid was triturated with ether, collected by filtration, washed with water and then ether, and dried under vacuum to give 4-chloro-6-methoxy-7-(2-(1,2,4-triazol-1-yl)ethoxy)quinazoline (756 mg, 65%). 1H NMR Spectrum (DMSO d6) 3.97(s, 3H); 4.65(dd, 2H); 4.70(dd, 2H); 7.39(s, 1H); 7.52(s, 1H); 7.99(s, 1H); 8.57(s, 1H); 8.89(s, 1H) MS-ESI: 306 [MH]+

Workup

  1. temperatureat reflux for 1 hour
  2. temperatureto cool
  3. customthe volatiles were removed by evaporation
  4. customThe residue was partitioned between methylene chloride and water
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. customThe residue was purified by column chromatography
  10. washeluting with methylene chloride/methanol (95/5)
  11. customThe purified solid was triturated with ether
  12. filtrationcollected by filtration
  13. washwashed with water
  14. dry with materialether, and dried under vacuum

Sources & evidence

ORD record
ord-fef7c23066264b08b13addff7b3beef4
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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