Multistep Microwave-Assisted Solvent-Free Organic Reactions: Synthesis of 1,6-Disubstituted-4-Oxo-1,4-Dihydro-Pyridine-3-Carboxylic Acid Benzyl Esters

摘要

The first examples for rapid synthesis of organic compounds using microwave ovens were reported by [1]. Since then a number of papers appeared concerning microwave-assisted organic reactions and the number of articles continues to grow quickly. The main advantages of microwave-assisted organic synthesis are shorter reaction times, minimum waste and generally higher yields. A particularly attractive feature of the microwave technique is the possibility of carrying out reactions in the absence of solvents. Within a general program on the utilisation of microwave enhanced organic reaction for the synthesis of biologically active compounds, in this paper we wish to report our results on the use of microwave technique in a multi-step synthesis of 1,6-disubstituted-4-oxo-1,4-dihydro-pyridine-3-carboxylic acid benzyl esters 9. Such compounds are of some interest for their biological activity. They present antibacterial and CNS stimulatory activity while the 6-methyl derivatives and related N-unsubstituted compounds are side-chain constituents in penicillins and cephalosporins possessing high activity vs Gram-negative organisms. On the other hand 4-oxo-1,4-dihydro-3-pyridine carboxylic acid derivatives have been studied, by a Glaxo research group, as inhibitors for DNA-Gyrase. Our multi-step approach, summarised in Schemes 1 and 2, takes into account the readily accessibility of phos-phonate 1 and the application of our recent developed synthesis of acetoacetate esters by means of microwave technique (Figure 1).