Reaction with, alkylating agents hydrazine

Hydrazinopyridazines such as hydralazine have a venerable history as anti hypertensive agents. It is of note that this biological activity is maintained in the face of major modifications in the heterocyclic nucleus. The key intermediate keto ester in principle can be obtained by alkylation of the anion of pi peri done 44 with ethyl bromo-acetate. The cyclic acylhydrazone formed on reaction with hydrazine (46) is then oxidized to give the aromatized compound 47. The hydroxyl group is then transformed to chloro by treatment with phosphorus oxychloride (48). Displacement of halogen with hydrazine leads to the formation of endralazine (49). ... 

On amination of 1,3,5-trimethyl- and 1,3,4,5-tetramethylpyrazoles with MSH, the corresponding N-aminopyrazolium salts were obtained (76CPB2267). The formation of A -aminopyrazoles by a recyclization reaction was described. Thus, on heating 5-halogeno- or 5-hydrazino-isooxazoles in anhydrous hydrazine, l-aminopyrazol-5-ones (11) are formed those can be converted further by various alkylating agents into... 

Condensation of ethyl acetoacetate with phenyl hydrazine gives the pyrazolone, 58. Methylation by means of methyl iodide affords the prototype of this series, antipyrine (59). Reaction of that compound with nitrous acid gives the product of substitution at the only available position, the nitroso derivative (60) reduction affords another antiinflammatory agent, aminopyrine (61). Reductive alkylation of 61 with acetone in the presence of hydrogen and platinum gives isopyrine (62). Acylation of 61 with the acid chloride from nicotinic acid affords nifenazone (63). Acylation of 61 with 2-chloropropionyl chloride gives the amide, 64 displacement of the halogen with dimethylamine leads to aminopropylon (65). ... 

Several therapeutic agents are based on phthalazinone nuclei, in which the hydrazide carbonyl group persists in unmodified form. Reaction of keto-acid (69-1) with hydrazine leads to the phthalazinone (69-2). Alkylation of the hydrazide nitrogen with 2-(chloroethyl)-A-methylpyrrolidine (69-3) surprisingly leads to the incorporation of a seven-membered azepine ring rather than the expected ethylpyrroldine. This can be explained by keeping in mind that it is likely that the... 

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