Amino pyridazinones, synthesis

The known methods lead to amino pyridazinones, which are useful intermediates for making agricultural and pharmaceutical chemicals, involving Raney-Ni cleavage of the hydrazino pyridazinone(7/, direct amination of the pyridazinones(72-74y), substitution of chloropyridazinone with ammonia at enhanced pressure( /5, and the dechlorination of chloropyridazinone performed in the presence of palladium on charcoal(7 / Therefore, we believe that a novel and convenient synthetic route is provided for the synthesis of aminopyridazinones, which are not easily accessible by traditional methods. 

The role of the pyridone ring as a pharmacophore in cardiotonic agents such as amrinone (25-6) has been noted earlier very analogous activity is obtained with compounds in which the heterocylic ring is replaced by a pyridazinone. The synthesis of the first of these agents, pimobendan (35-6), starts with the acylation of the amino group in nitro-aniline (35-2) with anisoyl chloride (35-1) to give amide (35-3). 

The most useful procedure utilises a 1,4-keto-ester giving a dihydro-pyridazinone, which can be easily dehydrogenated to the fully aromatic heterocycle, often by C-bromination then dehydrobromination alternatively, simple air oxidation can often suffice. 6-Aryl-pyridazin-3-ones have been produced by this route in a number of ways using an a-amino nitrile as a masked ketone in the four-carbon component, or by reaction of an acetophenone with glyoxylic acid and then hydrazine. Friedel-Crafts acylation using succinic anhydride is an alternative route to 1,4-keto-acids, reaction with hydrazine giving 6-aryl-pyridazinones. Alkylation of an enamine with a phenacyl bromide prodnces 1-aryl-l,4-diketones, allowing synthesis of 3-aryl-pyridazines. ... 

Microwave-assisted reactions of 5-amino-4-hydroxy-3(2//)-pyridazinone 114 with various carboxylic acid derivatives allowed a convenient and versatile approach to substituted 1,3-oxazolo[4,5-i/]pyridazinones 115. The developed methodology is suitable for rapid, parallel, automated synthesis of oxazolopyridazinone libraries <04TL4693>. 

Okushima, H., Narimatsu, A., Kobayashi, M., Furuya, R., Tsudo, K. and Kitada, Y. 1987. A novel class of cardiotonics. Synthesis and pharmacological properties of [4-(substituted-amino)phenyl]pyridazinones and related derivatives. J. Med. Chem. 30 1157-1161. 

---