[Potential antiallergic agents--synthesis and reactions of 1,4-dihydro-4-oxo-(1)benzofuro(3,2-b)pyridin-2-carboxylic acid esters].
The title compounds 5 were received from the saponification of ethyl 3-aminobenzo[b]furan-2-carboxylate (3) followed by reaction with acetylenedicarboxylic diesters. The esters 5 reacted with alkyl iodides to give mixtures of the 4-alkoxypyridines 8 and the N-alkylpyridones 9. Alkaline hydrolysis of the esters 5, 8 and 9 yielded the carboxylic acids 6, 11 and 12. The carboxylic acid 6 could be decarboxylated to afford the annulated pyridone 7. The tetrazoles 21 and 22 were synthesized starting from the esters 8 and 9. At first, reduction afforded carbinoles, subsequent selective oxidation yielded the aldehydes 15 and 16, which were converted into aldoximes. Dehydration of the aldoximes formed nitriles, which added hydrazoic acid. The carbaldehydes 15 and 16 reacted in the Hantzsch-Synthesis with beta-aminocrotonic 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 pyridine compound 27b was isolated as a by-product using 15b in the DHP-synthesis. The DHP 23 and 24 were more stable against oxidation than the reference drug nifedipine.
Görlitzer
K
K
Institut für Pharmazeutische Chemie, Technischen Universität Braunschweig, Germany. k.goerlitzer@tu-bs.de
Kramer
C
C
D000478:Alkylation; D018926:Anti-Allergic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry; D009543:Nifedipine / Q000737:chemistry; D010084:Oxidation-Reduction; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D013055:Spectrophotometry, Infrared
D018926:Anti-Allergic Agents; D001572:Benzofurans; D011725:Pyridines; D009543:Nifedipine