Polysubstituted and ring-fused pyridazine systems from tetrafluoropyridazine

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• 作者：Graham Pattison^a ; Graham Sandford^a ; ^{graham.sandford@durham.ac.uk} ; Ian Wilson^a ; Dmitrii S. Yufit^a ; Judith A.K. Howard^a ; John A. Christopher^b ; David D. Miller^b
• 关键词：Heterocyclic scaffold ; Perfluoroheterocycle ; Multi-functional pyridazine ; Nucleophilic aromatic substitution
• 刊名：Tetrahedron
• 出版年：2017
• 出版时间：2 February 2017
• 年：2017
• 卷：73
• 期：5
• 页码：437-454
• 全文大小：1663 K
• 卷排序：73

文摘

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.