Synthesis of the related substances of gefitinib

To strengthen the quality control over gefitinib and establish its quality criterion, four related substances of gefitinib were identified based on the synthetic route and synthesized, and their structures were confirmed by ¹H NMR and MS. These substances were 4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-ol( A ), N-(3-chloro-4-fluorophenyl)-6, 7-dimethoxyquinazolin-4-amine( B ), 4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)propylamino)ethanol( C )and N-(3, 4-dichlorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine( D ).