Polysubstituted and ring-fused pyridazine systems from tetrafluoropyridazine

Graham Pattison, Graham Sandford, Ian Wilson, Dmitrii S. Yufit, Judith A.K. Howard, John A. Christopher, David D. Miller

Research output: Contribution to journalArticle

Abstract

Tetrafluoropyridazine 1 reacts with a range of oxygen-, nitrogen-, sulfur- and carbon-centred nucleophiles to give, in general, products 2 arising from substitution of fluorine para to ring nitrogen. Subsequent reaction of the trifluoropyridazine derivatives 2 gave a range of 4,5-di- and tri-substituted products 3 and 6. Related reactions of tetrafluoropyridazine 1 with difunctional nucleophiles gave [6,6]-, [5,6]- and [6,5,6]-polycyclic ring fused pyridazine scaffolds 4 and 9. Further functionalisation of scaffolds 4 by nucleophlic aromatic substitution processes involving displacement of fluorine atoms at activated sites ortho to ring nitrogen provide an indication of the synthetic possibilities offered using tetrafluoropyridazine as a starting material for the preparation of polysubstituted pyridazine and novel polyfunctional ring fused pyridazine systems with potential applications in the drug discovery arena.

Original languageEnglish
Pages (from-to)437-454
Number of pages18
JournalTetrahedron
Volume73
Issue number5
DOIs
Publication statusPublished - 9 Dec 2016

Keywords

  • Heterocyclic scaffold
  • Multi-functional pyridazine
  • Nucleophilic aromatic substitution
  • Perfluoroheterocycle

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    Pattison, G., Sandford, G., Wilson, I., Yufit, D. S., Howard, J. A. K., Christopher, J. A., & Miller, D. D. (2016). Polysubstituted and ring-fused pyridazine systems from tetrafluoropyridazine. Tetrahedron, 73(5), 437-454. https://doi.org/10.1016/j.tet.2016.12.006