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

Participants

Reaction Steps

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]+

Provenance & Evidence