Growth vector elaboration of fragments: Regioselective functionalization of 5-hydroxy-6-azaindazole and 3-hydroxy-2,6-naphthyridine

Tools

Eliandro da Silva Júnior, Paulo, de Melo, Shaiani Maria Gil, de Paula, Murilo Helder, Vessecchi, Ricardo, Opatz, Till, Day, James E. H., Ganesan, A. and da Silva Emery, Flavio (2022) Growth vector elaboration of fragments: Regioselective functionalization of 5-hydroxy-6-azaindazole and 3-hydroxy-2,6-naphthyridine. Organic and Biomolecular Chemistry, 20 (37). pp. 7483-7490. ISSN 1477-0520

Full text not available from this repository. (Request a copy)

Abstract

This article discusses the reactivity of 6-azaindazole (1) and 2,6-naphthyridine (2), proposed to be “heteroaromatic rings of the future,” which would be useful for fragment-based drug discovery (FBDD) campaigns, developing growth vectors for fragment elaboration by selectively functionalizing different positions on the rings. The pyridone oxygens and pyrazole nitrogen can be functionalized selectively. Arylation at the α-carbon of the pyridone moiety was achieved by a transition metal-free radical cross-coupling using aryl hydrazines. This method proceeded under mild conditions without the need for protection of the hydroxypyridine. Additionally, we developed a method for the regioselective C-3 functionalization of heterocycle 1via N-sulfonamide rearrangement. This method involved a novel regioselective base-mediated N-C migration of the N-1 sulfonamide to yield the C-3 sulfone. This procedure is also applicable for indazole C-3 functionalization and mechanistic studies of the rearrangement suggest that an intermolecular process is involved. These reactions enable the fragment elaboration of heterocycles 1 and 2 in several growth vectors to facilitate their use in FBDD.

Item Type: Article
Additional Information: Funding Information: The authors are grateful to the funding agencies Sao Paulo Research Foundation (FAPESP. grants #2017/21146-6, #2016/24817-4 and #2013/26485-0), CAPES (grant SVR 119/2012), CNPq, and Astex Pharmaceuticals (UK) for a research grant, and to Dr J. C. Liermann (Mainz) for help with NMR spectroscopy and Dr C. J. Kampf (Mainz) for help with mass spectrometry. Publisher Copyright: © 2022 The Royal Society of Chemistry.
Uncontrolled Keywords: biochemistry,physical and theoretical chemistry,organic chemistry ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School: Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 11 Jan 2025 01:03
Last Modified: 28 Jan 2025 23:47
URI: https://ueaeprints.uea.ac.uk/id/eprint/98169
DOI:

Actions (login required)

View Item View Item