Pyrido pyridazine derivatives, synthesis

Reduced pyrido[4,3-c]pyridazines are obtained from piperidine derivatives such as (371) with hydra2dne e.g. 79AF1835), whilst another related synthesis coupled the enamine (372) with phenacyl bromide semicarbazone to give (373) (74JAP(K)7488897). 

Two complementary routes to the synthesis of pyrido[, y-i/ pyridazines have been developed, the first of which begins by constructing the pyridine ring, and the second by constmcting the pyridazine ring. In addition, ring transformations of pyrrolopyridine, pyridooxazine, pyridopyrimidine, and tetrazine derivatives to the pyrido[x,y-t7 pyridazines have also been reported. 

This type of reaction has been applied to the synthesis of a derivative 296 of the rare pyrido[4,3-c]pyridazine system (equation 121)148 and of l-arylpyrido[3,4-d]pyridazines 297 (equation 122)149. Cyclization of the enehydrazine 298 gives the 4-quinolone 299 (equation 123)150. 

The only other synthesis of a benzo fused derivative involves the pyridazino[4,3-c]isoquinoline series, the isoquinoline derivative (377) reacting with hydrazine to give (378) (74YZ607), although an s-triazolo-fused pyrido[2,3-with hydrazine and formic acid (56GEP951993). 

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