Streamlined Synthesis of 6-((1H-1,2,3-Triazol-4-yl)methyl)-1H-pyrrolo [3,4-d]pyridazin-1-one System via Sequential N-Alkylation, CuAAC, and [4 + 2] Cyclization Reactions

• Autor(a) principal: Bonacorso,Helio G.
• Data de Publicação: 2019
• Outros Autores: Magalhães,Hernane T., Forno,Gean M. Dal, Libero,Francieli M., Hoerner,Manfredo, Frizzo,Clarissa P., Martins,Marcos A. P., Zanatta,Nilo
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000601189
• topic: pyrroles; triazoles; pyrrolo[3,4-d]pyridazinones; N-alkylation; CuAAC; cyclocondensation reaction

An efficient sequential three-step reaction methodology for the synthesis of three new series-1-(prop-2-yn-1-yl)-1H-pyrroles, methyl 4-acetyl-1-((1H-1,2,3-triazol-4-yl)methyl)-1H-pyrrole-3-carboxylates and 6-((1H-1,2,3-triazol-4-yl)methyl)-2,6-dihydro-1H-pyrrolo[3,4-d]pyridazin-1-ones-is reported. The methodology comprises: (i) N-alkylation reactions of polyfunctionalized 1H-pyrroles-which were previously obtained from (E)-methyl 2-azido-3-arylacrylates-with propargyl bromide in order to obtain 1H-pyrroles; (ii) standard copper-catalyzed azide-alkyne cycloaddition (CuAAC) involving organic azides (benzyl-, 4-methoxybenzyl- and 4-chlorobenzyl, as well as n-octyl azide) and N-propargylated 1H-pyrroles to give triazolyl derivatives, as methyl 1H-pyrrole-3-carboxylates (click chemistry); and (iii) [4 + 2] cyclocondensation reactions of the ketoesters in the presence of hydrazine hydrochloride in order to furnish the desired series of pyrrolo[3,4-d]pyridazin-1-ones at total yields up to 54%.