2-Cyano-2- acetate reaction with hydrazine hydrate

With the aim of searching for synthetic approaches to new l,8-naphthyridin-2-one derivatives, transformations of ethyl 7-amino-l,4-dimethyl-2-oxo-l,2-dihydro-l,8-naphthyridine-6-carboxylate 363 were studied. Refluxing this compound with N,N-dimethylformamide dimethyl acetal in dry toluene afforded 7-[(Ar,Wdimethylami-nomethylene)amino]-l,8-naphthyridinone 364. The reaction of naphthyridone 363 with triethyl orthoformate produced ethoxymethyleneamino derivative 365. The reaction with hydrazine hydrate gave 7-amino-3-cyano-l,4-dimethyl-2-oxo-l,2-dihy-dro-l,8-naphthyridine-6-carbohydrazide 366 (2001S103). 

The reaction of 2-mercapto-4-(2, 4 -dichlorophenyl)-5-cyanopyrimidin-6(l//)one 421 (obtained by stirring ethyl cyanoacetate and thiourea with 2,4-dichlorobenzaldehyde in sodium ethylate at room temperature, in 70% yield), with a solution of monochloroacetic acid and />-cholorobenzaldehyde in glacial acetic acid, in the presence of sodium acetate, affords 2-[(/>-chlorophenyl)methylene]-6-cyano-7-(2, 4 -dichlorophenyl)thiazolo[3,2-tf]pyrimidin-3,5-dione 422. Finally, the reaction of compound 422 with hydrazine hydrate converts it into product 423 (Scheme 49) < 1996PS( 116)39>. 

The method can be used to cyclize ethyl 4-(butylamino)-5-cyano-6-formylpyridinc-3-carboxy-late with hydrazine hydrate in acetic acid at room temperature to give pyrido[2,3-c/]pyridazin-5(6//)-one 19 the 5-amino group of the intermediate apparently being exchanged for a hydroxy function in the course of the reaction.61... 

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