A telescoped protocol for the synthesis of new pyrrolo [3,4-d]pyridazinones by cascade reactions

• Published in: Tetrahedron letters Vol. 56; no. 37; pp. 5190 - 5195
• Main Authors: Bonacorso, Helio G., Libero, Francieli M., Dal Forno, Gean M., Pittaluga, Everton P., Porte, Liliane M.F., Martins, Marcos A.P., Zanatta, Nilo
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 09.09.2015; Elsevier
• Subjects: 2H-Azirines; Cascade reactions; Chemistry; Chemistry, Organic; Physical Sciences; Pyridazinones; Pyrrolo[3,4-d]pyridazinones; Science & Technology; Vinyl azides; Vinyl azides; Pyridazinones; Pyrrolo[3,4-d]pyridazinones; Cascade reactions; 2H-Azirines; MEDICINAL CHEMISTRY; 1,3-DICARBONYL COMPOUNDS; ONE-POT; BIOLOGICAL EVALUATION; FLUORINE; DERIVATIVES
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2015.07.035

[Display omitted] A new one-pot method, for the synthesis of polysubstituted pyrrolo[3,4-d]pyridazinones, is presented. The protocol consists in cascade reactions performed in the same media: (i) the thermal in situ pyrrole formation by the reaction of vinyl azides with 1,3-dicarbonyl compounds, via the 1,2-addition of 1,3-dicarbonyl compounds to 2H-azirine intermediates; (ii) the nucleophilic addition of hydrazines to the ketone group present in the pyrroles previously formed, followed by intramolecular cyclization with the bordering ester, which furnishes the respective pyrrolo[3,4-d]pyridazinones, substituted at the pyrrole and/or pyridazinone rings. All transformations occur in a two-step one-pot methodology, and a series of ten new compounds were obtained at yields of 42–87%.