Investigation of structure-activity relationships of novel quinazolines has identified 7,8-dihydro-[1,4]dioxino-[2,3-g]quinazolines as a potent inhibitor of EGFR. These compounds have a benzodioxane framwork, which was prepared by regioselective O-alkylation of ethyl 3,4-dihydroxy benzoate by epoxide ring opening. Compounds 3f and 3k were more potent than ZD-1839 in EGF enzyme and EGFR autophosporylation inhibition assays.