Traceless Solid-Phase Synthesis of Trisubstituted Quinazolines

Abstract

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.

Transition metal-free regioselective direct acylation of quinazolines for the synthesis of acylquinazoline derivatives

“…Thus, Krchňák developed a method for the construction of 4-benzoylquinazolines through multistep reactions of polymer-supported Fmoc-α-amino acid, 2-nitrobenzenesulfonyl chloride and α-bromoacetophenones (Scheme 1a). 3 Wu described a protocol for the synthesis of acylquinazolines via C–H activation/annulation of N -arylamidines and sulfoxonium ylides (Scheme 1b). 4 Recently, Hwang reported a visible light-induced photo-redox copper-catalyzed oxidative Csp 2 –H annulation of amidines with terminal alkynes to construct 4-acylquinazolines (Scheme 1b).…”