| Full text | |
| Author(s): |
da Silva Junior, Paulo Eliandro
;
Gil de Melo, Shaiani Maria
;
de Paula, Murilo Helder
;
Vessecchi, Ricardo
;
Opatz, Till
;
Day, James E. H.
;
Ganesan, A.
;
Emery, Flavio da Silva
Total Authors: 8
|
| Document type: | Journal article |
| Source: | ORGANIC & BIOMOLECULAR CHEMISTRY; v. 20, n. 37, p. 8-pg., 2022-08-26. |
| 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 alpha-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. (AU) | |
| FAPESP's process: | 16/24817-4 - Development of selective functionalization of novel heterocycles |
| Grantee: | Paulo Eliandro da Silva Júnior |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 13/26485-0 - Development of new ligands for Peroxisome Proliferator-Activated Receptor by an approach of fragment based drug discovery |
| Grantee: | Paulo Eliandro da Silva Júnior |
| Support Opportunities: | Scholarships in Brazil - Doctorate |