Ethyl 1,4-Dihydro-4-oxo-1,8-naphthyridine-3-carboxylates by a Tandem SNAr-Addition-Elimination Reaction

A series of N-substituted 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate esters has been prepared in two steps from ethyl 2-(2-chloronicotinoyl)acetate. Treatment of the beta-ketoester with N,N-dimethylformamide dimethyl acetal in N,N-dimethylformamide (DMF) gave a 95% yield of the 2-dimethylaminomethylene derivative. Subsequent reaction of this beta-enaminone with primary amines in DMF at 120oC for 24 h then afforded the target compounds in 4782% yields by a tandem SNAr-addition-elimination reaction. Synthetic and procedural details as well as a mechanistic rationale are presented.