N,N-Dimethylaniline → 7-((2-Chloro-4-pyridyl)methoxy)-4-(2-fluoro-5-hydroxy-4-methylanilino)-6-methoxyquinazoline hydrochloride

Participants

Reaction Steps

A mixture of 7-((2-chloro-4-pyridyl)methoxy)-6-methoxy-3,4-dihydroquinazolin-4-one (150 mg, 0.47 mmol), phosphoryl chloride (0.2 ml) and N,N-dimethylaniline (0.2 ml) in toluene (5 ml) was heated at reflux for 1 hour. The volatiles were removed by evaporation and the residue was partitioned between ethyl acetate and saturated sodium hydrogen carbonate solution. The organic layer was separated, dried (MgSO4) and the solvent removed by evaporation. A solution of 2-fluoro-5-hydroxy-4-methylaniline (67 mg, 0.47 mmol), (prepared as described for the starting material in Example 13), in isopropanol (10 ml) was added to the solid residue and the mixture was heated at reflux for 2 hours. The mixture was allowed to cool and the precipitated product collected by filtration, washed with acetone and dried to give 7-((2-chloro-4-pyridyl)methoxy)-4-(2-fluoro-5-hydroxy-4-methylanilino)-6-methoxyquinazoline hydrochloride (70 mg, 30%). m.p. 245-250° C. 1H NMR Spectrum: (DMSOd6) 2.30(s, 3H); 4.10(s, 3H); 5.45(s, 2H); 6.90(d, 1H); 7.10(d, 1H); 7.35(s, 1H); 7.50(d, 1H); 7.65(s, 1H); 8.25(s, 1H); 8.45(d, 1H); 8.75(s, 1H); 9.60(br s, 1H); 11.30(s, 1H) MS-ESI: 441 [MH]+

Provenance & Evidence