Phthalazinones cyclocondensation

Quinolyl)pyrazoIo[3,4-i7]pyridazincs were prepared by cyclocondensation reactions of an anilino-pyrazole acid with acetaldehyde <02JHC869>. Cyclopentadienyl-derived y-diketones and arylhydrazines condensed to 4-(l,4-diaryl-2//-cyclopent[d]pyridazin-2-yl)-benzenesulfonamides <02H(57)2383>. Sulfonated polyfphthalazinone ether sulfone)s 37 were prepared by polycondensation of 4-(4-hydroxyphenyl)phthalazinone 36 with various ratios of disodium 5,5 -sulfonylbis(2-fluorobenzenesulfonate) and bis(4-fluorophenyl)sulfone <02P5335>. 

The reactivity of pyridazines in Pd-catalyzed reactions was of interest. For example, the Heck alkenylation at C5 of 6-phenyl-3(2//)-pyridazinones was investigated, with the aim of suppressing production of 4-phenyl-6-substituted-2-phthalazinone byproducts <04TL3459>. In another study, the reactivity of 5-iodopyridazin-3(2f/)-ones in Pd-catalyzed reactions was investigated to develop an efficient route to 2,5-disubstituted pyridazin-3(2/f)-ones <04T12177>. Other pyridazine syntheses relied on condensation approaches. Benzo[g]pyridazino[l,2-i>]-phthalazine-6,13-diones 16 and 17 related to certain anthracyclinones were obtained by cycloaddition of 1,3-dienes to benzo[g]phthalazine-l,4-dione <04H(63)1299>, and pyridazine C-nucleosides synthesized by 14-i-2 cyclocondensation of alkynyl C-nucleosides with substituted tetrazines afforded, upon extrusion of a nitrogen atom, pyrrole C-nucleosides in good yields... 

Such substrates clearly should afford 1-phthalazinamines, but the only reported examples underwent concomitant or subsequent hydrolysis under the conditions of cyclocondensation to give the corresponding phthalazinones 3-formylphthalonitrile (52) gave 4-oxo-3,4-dihydro-5-phthalazinecarbonitrile (53) (H2NNH2 H2O, 12M HCl, PhH, reflux, 6h 66%). ... 

The cyclocondensation of these substrates with hydrazines is represented by only one example. Methyl o-cyanobenzoate (116) with methylhydrazine gave 4-amino-2-methyl-l(2H)-phthalazinone (117) (MeONa, MeOH, 20°C, 12 h 24%). " ... 

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