Efficient synthesis of 3-aryl-1-(4-{[3-(3-methoxyphenyl)- [1,8]naphthyridin- 2- yl]amino}phenyl)-2-propen-1-ones

Abstract

Interaction of 2-chloro-3-(3-methoxyphenyl)[1,8]naphthyridine 48 with 4-aminoacetophenone 49 in the presence of K2CO3 in the solid state grinding conditions at RT furnished 1-(4-{[3-(3-methoxyphenyl)[1,8]naphthyridin2-yl]-amino}-phenyl)-1-ethanone 51 in 95% yield. Claisen-Schmidt condensation of 1-(4-{[3-(3-methoxyphenyl)- [1,8]naphthyridin-2-yl]amino}phenyl)-1-ethanone 51 with various aromatic aldehydes in the presence of pTSA(ptoluenesulphonic acid) in solvent-free grinding conditions at RT afforded the corresponding 3-aryl-1-(4-{[3-(3- methoxyphenyl)[1,8]naphthyridin-2-yl]amino}phenyl)-2-propen-1-ones52 by Claisen-Schmidt condensation (Chalcones or , -unsaturated ketones) (Scheme I). Reactions are not time consuming and the yields of the products are very good. The reaction did not proceed at all when performed without PTSA. The process is environmentally benign and the experimental procedure is very simple. The Whatman filter paper discs (6 mm diameter) with different compounds were placed aseptically on seeded nutrient agar plates with different bacteria and incubated for 72 hr at 37 + 1 oC. The presence of substituents especially methyl, chloro, fluoro and dimethoxy groups when attached to phenyl ring increases the anti bacterial activity notably. Zone of inhibition was screened in mm