Facile synthesis of novel amino acid-like building blocks by N-alkylation of heterocyclic carboxylates with N-Boc-3-iodoazetidine.

Abstract

An efficient protocol providing easy access to highly functionalized heterocyclic compounds as novel organic building blocks was developed by coupling alkyl pyrazole-, indazole- and indolecarboxylates with N-Boc-3-iodoazetidine. The synthesized compounds are representatives of constrained non-chiral synthetic azole carboxylates in their N-Boc protected ester forms. Diversification of the prepared heterocyclic building blocks was achieved via application of palladium-catalyzed Suzuki-Miyaura cross-coupling reactions. In total, 34 building blocks were obtained to form a highly diversified small molecule collection. The structure of the novel heterocyclic compounds was investigated and verified by advanced NMR spectroscopy methods.