Pyrido pyridazines, reaction with enamines

The slightly lower lowest unoccupied molecular orbital (LUMO) energy of pyrido[3,4-r71pyridazine 5 compared to its isomer [2,3-r7] 6, calculated by the AMI method <1985JA3902>, explained the shorter time required for the pyrido[3,4-r7j-pyridazine to complete the [4+2] cycloaddition reaction with cyclic enamines of different ring sizes <1995M211, 2001ARK21>. 

Pyrido[2,3-, pyridazine derivatives 48 have been synthesized by refluxing equimolar amounts of an appropriate 5-benzylidene-2,2-dimethyl-l,3-dioxane-4,6-dione 47 with 5-amino-6-phenylpyridazin-3(2/7)-one 46 in methanol or a methanol acetic acid mixture. The electron-poor carbon atom of the polarized carbon-carbon double bond of 47 is the electrophile attacking C-4 of the 5-aminopyridazinone 46. Imino-enamine tautomerization of the intermediate is followed by ring closure and subsequent loss of acetone and carbon dioxide affording the reaction products 48 as stable crystalline solids in 70-90% yield (Scheme 9) <2000T2473>. 

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