Gyrase inhibitors Part 3.: Synthesis and reactions of ethyl 1,4-dihydro-4-oxo-[1]benzothieno[3,2-b]pyridine-3-carboxylate

The title compound 4a is synthesized from potassium 3-aminobenzo[b]thiophen e-2-carboxylate (1) by Gould-Jacobs reaction. Compound 4a reacts with alkyl halides and sodium hydride in DMF to yield the N-alkylpyridones 5a-e as we ll as the 4-alkoxypyridines 6a-c; with phosphoryl chloride the 4-chloropyri dine 7a is obtained. The carboxylic acids 4b, 5d, 5e, 6d and 7b are receive d by alkaline saponification of the esters 4a, 5a-c, 6a-c and 7a. The carbi noles 8 and 9, formed by boranate reduction of the esters 6a and 7a, are tr ansformed to the aldehydes 10 and 11 by activated manganese dioxide oxidati on. The aldoxime 12 from the carbaldehyde 11 is dehydrated to yield the nit rile 13. The carbaldehyde 11 reacts with methyl beta-aminocrotonate to yiel d the 1,4-dihydropyridine (DHP) 14, which is dehydrogenated to give the 3,4 '-bipyridine 15. The pyridone 4a reacts with tosylisocyanate to yield the 4 -tosylaminopyridine 16a. The antibacterial activity of the carboxylic acids 4b, 5d, 5e and 6d is proved. The growth of Escherichia coli and Bacillus m egaterium is inhibited by 5d in the same range as nalidixic acid does.