Synthesis and Antimicrobial Activity of Pyrazole Derivatives of 2-Cyclopropyl-1,8-naphthyridines

Abstract

2-Amino-pyridine-3-carboxaldehyde and 3-cyclopropyl-3- oxopropionic acid ethyl ester react each other to provide 2-cyclopropyl- [1,8]-naphthyridin-3-carboxylic acid ethylester (1) which reacts with 99 % hydrazine hydrate to yield 2-cyclopropyl-[1,8]-naphthyridine-3- carboxylic acid hydrazide (2). This acid hydrazide (2), reacts with different acetophenones to yield respective Schiff bases (3a-h). Compounds 3a-h react with Vilsmeier-Haack reagent (DMF/POCl₃) to furnish 1-(2- cyclopropyl-[1,8]-naphthyridine-3-carbonyl)-3-phenyl-1H-pyrazole-4- carbaldehydes (4a-h). 2-Cyclopropyl-[1,8]-naphthyridine-3-carboxylic acid hydrazide (2) on reaction with substituted acetylacetones and substituted ethyl acetoacetates gives substituted 2-cyclopropyl-[1,8]- naphthyridin-3-yl)-(3,5-dimethyl-pyrazol-1-yl)-methanones (5a-d) and 2-(2-cyclopropyl-[1,8]-naphthyridine-3-carbonyl)-5-methyl-2,4- dihydropyrazol-3-ones (6a-c), respectively. On the other hand, hydrazide (2) reacts with different aromatic aldehydes yields 2-cyclopropyl-[1,8]- naphthyridine-3-carboxylic acid benzylidene-hydrazides (7a-g). Compounds (7a-g) on reaction with mercapto-acetic acid offered 3-[(2-cyclopropyl- [1,8]-naphthyridin-3-yl-methyl)amino]phenyl-thiazolidin-4-ones (8a-g). Interaction of acid hydrazide (2) with different aromatic acid chlorides afford N'-acetyl/benzoyl-2-cyclopropyl-1,8-naphthyridine-3-carbohydrazides (9a-d), which on treatment with POCl₃ yield 2-cyclopropyl- [1,8]-naphthyridin-3-yl)-(5-phenyl-[1,3,4]-oxadiazol-2-yl)methanone (10a-d).