L- -pyridazinone

A solution of 223.2 g of 6concentrated hydrochloric acid is heated to the boil at reflux for 22 hours while stirring. The mixture Is concentrated in a vacuum, and the resulting crude crystalline hydrochloride of 5,6,73-tetrahydro-3(2H)pyrido[4,3melting point of 307°C to 310°C (decomposed from methanol), is suspended in 0.75 liter of methanol, and... 

Also some 4(l//)-pyridazinones [121] and several 3-(aminoalkylthio)-6-chloropyridazines [269] have been claimed as useful antithrombotic agents. In... 

The dicarbonyl compounds used in these syntheses comprise 1,2-diketones, a-ketoacids, or glyoxal, and esters with a reactive a-methylene group are represented by malonic, acetoacetic, cyano-acetic, benzoylacetic, or hippuric esters. Many 4-, 5-, and/or 6-sub-stituted 3(2/l)-pyridazinones have thus been synthesized in reasonable yields. 

Protected /3-D-ribofuranose and 3(2//)-pyridazinones gave the N-glucosides, whereas 4-amino-3-chloro-6(l//)-pyridazinone afforded the O-glycoside (87MI27). In the formation of pyridazine cyclonucleosides, either the 2 - (75) or 5 -hydroxy group (76) was involved in ring formation (83JOC3765). 

Arylhydrazones of pentane-2,3,4-trione, when treated with NaH and acetyl chloride or chloroacetyl chloride, were transformed into 1-aryl-4(l//)-pyridazinones or 2-aryl-3(2A/)-pyridazinones, respectively [91IJC(B)932 92IJC(B)273]. 

From 3-hydrazino-6(l//)-pyridazinone and protected /3-D-ribofuranose the nucleoside 142 (R=Bz) was prepared and after deprotection with sodium methoxide 142 (R=H) was obtained (89MI6).The pyridazine analog of 2 -deoxycitidine was synthesized from 3-methoxy-6-chloropyridazine by intramolecular glycosylation of 143. Compound 143 was treated with Me2S(SMe)BF4 and the oxonium intermediate was hydrolyzed to give the 2 -deoxynucleoside 144 (95MI4). 

Stable diazonium salts were obtained upon nitrosation of 5-amino-2-phenyl-4-chloro-6(l//)-pyridazinone 98, whereas the diazonium salt prepared from 4-amino-5-chloro analog 99 is unstable and highly reactive (83MI15). Diazotization of 5-aminopyridazin-4-yl-p-chlorophenyl ketone gave the corresponding 4-one [86JCS(P1)169]. 

The orientation of reaction of aminopyridazines with electrophiles, and further reaction of the intermediates is illustrated by a study with 4-amino-5-aroylpyridazines. Acylation and sulfonylation occurs on the amino nitrogen, while alkylation occurs, as expected, at N-1 the acylamino derivatives are relatively unstable, but the toluenesulfonamide is quite stable to acid and to base. Methylation of the toluenesulfonamide gives a mixture of ring and amino alkylated products with the latter predominating. Hydrolysis of the ring A-alkylated compounds gives 4(l//)-pyridazinones (Scheme 57). Selective amino-alkylation of the 4-amino-5-aroylpyridazines is achieved via the imidate by reduction and subsequent oxidation of the alcohol <85H(23)265l>. 

The synthesis of pyridazine derivatives from hydrazones includes the thermal cyclization of 2-arylhydrazono-3-oxo-5-phenyl-4-pentenenitriles (readily obtained from ethyl cinnamate by condensation with acetonitrile followed by Japp-Klingemann type reactions) to l-aryl-3-cyano-6-phenyl-5,6-dihydro-4(l//)-pyridazinones (Scheme 85) <86JHC93>, and base-induced cyclization of a hydrazone of a 4-chloro-l-arylbutan-l-one to prepare a 2,3,4,5-tetrahydropyridazine (Scheme 85) <88JHC1543>. An earlier route to 6-carboxy-5-hydroxy-2-phenyl-3(2//)-pyridazinone via condensation of benzenediazonium chloride and dimethyl acetonedicarboxylate has been adapted to give a series of aryl derivatives either as esters (by thermal cyclization) or as acids (by cyclization with hydroxide). Both cyclizations proceed in high overall yield (Scheme 86) and decarboxylation of the acids also proceeds in high yield <89JHC169>. 

Chloro-4(l//)-pyridazinones are made in moderate to good yields in an unusual synthesis from... 

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