Synthesis of novel 1,7‐naphthyridines by Friedländer condensation of pyridine substrates

Abstract

in Wiley Online Library (wileyonlinelibrary.com).The general ability of appropriate pyridyl compounds (aldehyde or ketone) to undergo Friedländer condensation to give different 1,7-naphthyridines has been demonstrated. 2,4-Disubstituted 1,7-naphthyridine 8 was prepared from 3-amino-4-acetylpyridine (6) and ketone 4 (82%). The Friedländer self-condensation of pyridyl substrate 6 is reported, as well. The dimer product, 2-(3-aminopyridin-4-yl)-4-methyl-1,7-naphthyridine (7), was obtained in 97% yield. 2-Aryl-and 2,3-diaryl-1,7-naphthyridines (16-18) were prepared from 3-aminoisonicotinaldehyde (13) and arylketones 4, 14, and 15 (28-71%). The key substrates 6 and 13 are readily available via the improved pyridine nitration method.

Design, Synthesis, and Biological Evaluation of 4-Quinoline Carboxylic Acids as Inhibitors of Dihydroorotate Dehydrogenase

“…However, reactions involving PCC oxidation 35 or a reusable poly aniline catalyst 36 on 1,6-aza-indoles did not provide the desired 1,6aza-isatin. Inspired by the work of Stockmann et al 37 and Zong et al, 38 we sought to generate our naphthyridine series by installing an α-keto ester on an aminopyridine amide precursor, 38 which would provide an intermediate for a subsequent Pfitzinger condensation. Drawing on the work of Turner et al, 39 Meanwell et al, 40 and Zong et al, 38 The synthesis of C6-substituted 1,7-naphthyridines presented an obstacle for SAR evaluation.…”