An efficient synthesis of dimethyl 1-alkyl-4-hydroxy-6-oxo-1,6-dihydropyridine-2,3-dicarboxylates is described. This involves a three-component reaction between primary alkylamines, malonyl dichloride, and dimethyl acetylenedicarboxylate.The 2-pyridone core structure is an important heterocyclic framework that can be found in numerous biologically active compounds. It is also a versatile synthon that can be further transformed to pyridine, piperidine, quinolizidine, and indolizidine alkaloids. 1 N-Alkylated 2-pyridones are important intermediates in the synthesis of polycyclic compounds of biological significance. 2 The broad range of applications of the 2-pyridone structural motif has resulted in several synthetic methods. 3 The most versatile and useful strategy to produce pyridine derivatives is condensation between 1,3-dicarbonyl compounds and 3-aminoenones, 3-aminoacrylates, or cyanoacetamides. 4 In addition, construction of pyridine and pyridone rings by metal-mediated [2+2+2]-cycloaddition reaction of alkynes with nitriles or isocyanates, is an efficient method and has been largely developed. 5Recently, multicomponent condensation reactions have become a powerful method for the synthesis of small-molecule libraries, due to the fact that products are formed in a single step by simultaneous reactions of several reagents and the molecular diversity required for such combinatorial libraries can be achieved by simply varying each component. 6As part of our current studies on the development of new routes in heterocyclic synthesis, 7 we report an efficient synthesis of functionalized 2-pyridones. Thus, the reaction of alkylamines 1 with dimethyl acetylenedicarboxylate [DMAD (2)] in the presence of malonyl dichloride (3) led to dimethyl 1-alkyl-4-hydroxy-6-oxo-1,6-dihydropyridine-2,3-dicarboxylates 4 in excellent yields 8 (Scheme 1).The structures of compounds 4a-g were apparent from their mass spectra, which displayed in each case, the molecular ion peak at the appropriate m/z values. The 1 H NMR and 13 C NMR spectroscopic data, as well as IR spectra, are in agreement with the proposed structures. The 1 H NMR spectrum of 4a in CDCl 3 showed five singlets for methoxy (d = 3.69 and 3.85 ppm), methylene (d = 5.19 ppm), methine (d = 5.89 ppm), and OH (d = 10.78 ppm) protons, along with characteristic multiplets for the aromatic protons. The 13 C NMR spectrum of 4a exhibited fourteen signals in agreement with the proposed structure. 8 The 1 H NMR and 13 C NMR spectra of 4b-g were similar to those of 4a except for the aryl moieties, which showed characteristic resonances in appropriate regions of the spectrum.A tentative mechanism for this transformation is proposed in Scheme 2. It is conceivable that the initial event is the formation of enaminone 6 from the amine and DMAD, 9,10 which is subsequently attacked by malonyl dichloride to produce 7. Intermediate 7 undergoes cyclization reaction, HCl elimination, and keto-enol tautomerism to generate 4.In conclusion, we have described a convenient route to functionalized ...