Facile synthesis of novel 7-aminofuro- and 7-aminothieno[2,3-d]pyridazin-4(5H)-one and 4-aminophthalazin-1(2H)-ones


Koza G., Keskin S., Ozer M. S. , Cengiz B., ŞAHİN E., BALCI M.

TETRAHEDRON, vol.69, no.1, pp.395-409, 2013 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 69 Issue: 1
  • Publication Date: 2013
  • Doi Number: 10.1016/j.tet.2012.10.010
  • Title of Journal : TETRAHEDRON
  • Page Numbers: pp.395-409
  • Keywords: Pyridazinone, Furopyridazinone, Thienopyridazinone, Phthalazinone, Acyl azide, Curtius rearrangement, PALLADIUM-CATALYZED SYNTHESIS, CARDIOTONIC AGENTS, BENZAL)HYDRAZONE DERIVATIVES, RECEPTOR ANTAGONISTS, HOMOPHTHALIC ACID, PART 10, PYRIDAZINES, INHIBITORS, SKELETON, CONSTRUCTION

Abstract

We hereby report the synthesis of a novel class of compounds, 7-aminofuro- and 7-aminothieno[2,3-d]pyridazin-4(5H)-one and 4-aminophthalazin-1(2H)-ones starting from methyl 2-(2-methoxy-2-oxoethyl)furan- and thiophene-3-carboxylate and methyl 2-(2-methoxy-2-oxoethyl)benzoate. The ester functionalities connected directly to the aromatic ring were regiospecifically converted to the acid, whereas methylene groups were oxidized to the corresponding ketoesters. Reaction of the ketoesters with hydrazine provided the hydrazone derivatives. An intramolecular cyclization in the presence of thionyl chloride formed a fused pyridazinone skeleton. Hydrolysis of the remaining ester groups and transformation of the acid functionalities to the acyl azides followed by Curtius rearrangement gave the isocyanates. Reaction of the isocyanates with methanol and water produced urethane and amino-pyridazinone derivatives, respectively. (C) 2012 Elsevier Ltd. All rights reserved.