7-(Benzyloxy)-4-chloro-6-methoxyquinazoline hydrochloride → 7-Benzyloxy-4-(2-fluoro-5-hydroxy-4-methylphenoxy)-6-methoxyquinazoline

HRID 1384550Notes

Reaction equation

HRID 1384550 reaction equation
Cl.[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14](Cl)=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[F:23][C:24]1[CH:29]=[C:28]([CH3:30])[C:27]([O:31]C(OC)=O)=[CH:26][C:25]=1[OH:36]>N1C=CC=CC=1>[CH2:2]([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([O:36][C:25]3[CH:26]=[C:27]([OH:31])[C:28]([CH3:30])=[CH:29][C:24]=3[F:23])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:21][CH3:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 220308367-(Benzyloxy)-4-chloro-6-methoxyquinazoline hydrochlorideHCID 22625031(4-Fluoro-5-hydroxy-2-methylphenyl) methyl carbonate

Product 1

HCID 158860437-Benzyloxy-4-(2-fluoro-5-hydroxy-4-methylphenoxy)-6-methoxyquinazolineYield 73.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (132 mg, 0.4 mmol), (prepared as described for the starting material in Example 1), and 2-fluoro-5-methoxycarbonyloxy-4-methylphenol (96 mg, 0.48 mmol) in pyridine (2 ml) was heated at reflux for 3 hours. The mixture was allowed to cool, the solvent was removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with water, brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/ether (70/30). The resulting solid was crystallised from methylene chloride and methanol to give 7-benzyloxy-4-(2-fluoro-5-hydroxy-4-methylphenoxy)-6-methoxyquinazoline (120 mg, 64%). 1H NMR Spectrum: (DMSOd6) 2.15(s, 3H); 3.98(s, 3H); 5.35(s, 2H); 6.75(d, 1H); 7.13(d, 1H); 7.37(d, 1H); 7.45(t, 2H); 7.48-7.56(m, 3H); 7.58(s, 1H); 8.54 (s, 1H); 9.65(br s, 1H) MS-ESI: 454 [MH]+

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hours
  3. temperatureto cool
  4. customthe solvent was removed by evaporation
  5. customthe residue was partitioned between ethyl acetate and water
  6. customThe organic layer was separated
  7. washwashed with water, brine
  8. dry with materialdried (MgSO4)
  9. customthe solvent removed by evaporation
  10. customThe residue was purified by column chromatography
  11. washeluting with methylene chloride/ether (70/30)
  12. customThe resulting solid was crystallised from methylene chloride and methanol

Sources & evidence

ORD record
ord-33f76b8c22b14b059ba287d72138d012
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

Loading…