A traceless polymer-supported synthesis of 4-benzoylquinazolines was developed using the following commercially available building blocks: Fmoc-α-amino acids, 2-nitrobenzensulfonyl chlorides and α-bromoacetophenones. The acyclic intermediates underwent base-catalyzed rearrangement involving C-C and N-N bond formation followed by ring expansion and yielded resin-bound dihydroquinazoline-2-carboxylic acids. After they were released from the resin by treatment with trifluoroacetic acid, base-mediated decarboxylation produced the target quinazolines in moderate-to-high yields and purities.
Keywords: amino acids; bromoketone; indazole oxides; nitrobenzenesulfonyl chlorides; quinazolines; solid-phase synthesis; traceless synthesis; α-bromoacetophenones.