Hydrazine pyridazine-3-carboxamide

The majority of pyrimido[4,5-c]pyridazines have been prepared from pyrimidine precursors. The chloropyrimidines (176) give the desired heterocyclic ring (177) on reaction with hydrazine (72BSF1483). Hydrazine also reacts with ethyl a-diazo-/3-oxo-5-(4-chloro-2-methylthiopyrimidine)propionate (178) to give the pyrimido[4,5-c]pyridazine-3-carboxamide (78). A mechanism for this interesting reaction has been proposed as shown, on the basis of the detection of hydrogen azide in the reaction mixture. There is no precedent for the reaction of the a-carbon of a-diazo-/3-oxopropionates with nucleophiles under basic conditions (76CPB2637). 

In a similar fashion, as carboxylic acids or their esters, certain carboxamides possessing an ortho acyl group tnay also cyclocondense with hydrazine. Thus, Ar,/V-dicthyl-3-(2-pyridy car-bonyl)pyridine-2-carboxamide gives the corresponding pyrido[2,3-(i]pyridazin-H(7//)-one 15 in 89% yield, whereas, in contrast, 3-benzoyl-A, Ar-diisopropylpyridine-2-carboxamide and hydrazine give jV,2V-diisopropyl-5-phenylpyrido[2,3-d]pyridazin-8-amine (16) in 42% yield.50... 

Treatment of ethyl 5-acetyl-3-carbamoyl-2-methylisonicotinate with hydrazine dihydrochloride gives 4,7-dimethyl-l-oxo-l,2-dihydropyrido[3,4-[Pg.55]

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