Treatment of ethyl 2,6-dichloro-5-fluoronicotinylacetate (I) with ethyl orthoformate in refluxing acetic anhydride and then with 2,4-difluoroaniline in methylene chloride at room temperature gives the enaminoketo ester derivative (II). Cyclization of (II) with sodium hydride in THF gives ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (III). Hydrolysis of (III) with hydrochloric acid yields 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (IV). Condensation of (IV) with 3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidine (V) in pyridine yields 7-(3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidin-1-yl)- 1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (VI). Hydrolysis of (VI) in trifluoroacetic acid gives A-70826.

Treatment of ethyl 2,6-dichloro-5-fluoronicotinylacetate (I) with ethyl orthoformate in refluxing acetic anhydride and then with 2,4-difluoroaniline in methylene chloride at room temperature gives the enaminoketo ester derivative (II). Cyclization of (II) with sodium hydride in THF gives ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (III). Hydrolysis of (III) with hydrochloric acid yields 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (IV). Condensation of (IV) with 3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidine (V) in pyridine yields 7-(3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidin-1-yl)- 1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (VI). Hydrolysis of (VI) in trifluoroacetic acid gives A-70826.