Synthesis and reactions of 1,4-dihydro-4-oxo-[1]benzofuro[3,2-b]pyridine-2-carboxylic acid esters

The title compounds 5 were received from the saponification of ethyl 3-amin obenzo[b]furan-2-carboxylate (3) followed by reaction with acetylenedicarbo xylic diesters. The esters 5 reacted with alkyl iodides to give mixtures of the 4-alkoxy-pyridines 8 and the N-alkylpyridones 9. Alkaline hydrolysis o f the eaters 5, 8 and 9 yielded the carboxylic acids 6, 11 and 12. The carb oxylic acid 6 could be decarboxylated to afford the annulated pyridone 7. T he tetrazoles 21 and 22 were synthesized starting from the esters 8 and 9. At first, reduction afforded carbinoles, subsequent selective oxidation yie lded the aldehydes 15 and 16, which were converted into aldoximes. Dehydrat ion of the aldoximes formed nitriles, which added hydrazoic acid. The carba ldehydes 15 and 16 reacted in the Hantzsch-Synthesis with beta-aminocrotoni c acid esters to form the 1,4-dihydropyridines (DHP) 23 and 24, which could be dehydrogenated to obtain the pyridines 25 and 26. The unsymmetrical pyr idine compound 27b was isolated as a by-product using 15b in the DHP-synthe sis. The DHP 23 and 24 were more stable against oxidation than the referenc e drug nifedipine.