Unusually mild and efficient synthesis of functionalized spiro-substituted 1,2,3,4-tetrahydro- nicotinamides by the michael reaction

The use of chalcogen amides of cyanoacetic acid in the synthesis of nicotinic acid nitriles by means of the Michael reaction is well known [1–3]. On the other hand, the transformation of the nitrile group as a substituent in the pyridine ring into an amide [4], ester [5], or acid group [6] requires relatively rigorous conditions, similar to most reactions of nitriles [7]. We have found that cyclopentylidenecyanoacetamide 1a and cyclohexylidenecyanoacetamide 1b react under conditions of the Michael reaction with acetoacetanilide 2a or ethyl acetoacetate 2b to give functionalized spiro-substituted 1,2,3,4-tetrahydronicotinamides 3a,b in good yields. The mechanism for the transformation of the nitrile group into an amide group, the scope of this reaction, and the chemical and biological properties of products 3a,b are under investigation.