Ethionamide Ethanol

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Ethinylestradiol Ethanedisulfonic acid Caramiphen edisylate Ethanol Alibenol Benoxinate HCI Bufexa mac Clobazam Clofibrate Dicyclomine HCI Ethionamide Ethoheptazine Etiroxate Exalamide Feprazone Floredil HCI Flurbiprofen Gramicidin Heptabarbitol Ibuprofen Ibuproxam Insulin Ketoprofen Lofexidine HCI Mebeverine HCI Meperidine HCI Methitural... 

Ethionamide (2-ethylthioisonicotinamide, Trecator SC, 8) is an antibiotic prodrug used in the treatment of tuberculosis. One synthetic pathway involves the condensation of diketo-ester 160 with cyanoacetamide 161 followed by hydrolysis of the resulting pyridone 162 into give pyridone acid 163. Treatment of 163 with POCI3 converts the lactam to imine chloride and simultaneous ester formation in ethanol to give 164. Hydrogenation of 164 to remove the chloride, amide formation, and sequential conversion to the thioamide provided 8." ... 

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