PEG-400 promoted a simple, efficient and eco-friendly synthesis of functionalized novel isoxazolyl pyrido[2,3-d]pyrimidines and their antimicrobial and anti-inflammatory activity

Abstract

A simple, efficient, cost-effective and environmentally friendly synthesis of new isoxazolyl pyrido[2,3-d]pyrimidine derivatives 11 has been developed from 4-amino-3-methyl-5-styrylisoxazoles 7 by using polyethylene glycol-400 (PEG-400) as a solvent as well as catalyst. Compound 7 on treatment with methyl-2-chloronicotinate 8 in the presence of PEG-400 to obtain the corresponding (E)-methyl-2-((3-methyl-5-styrylisoxazol-4-yl)amino)nicotinates 9, which was further treated with different arylisothiocyanates 10 in the presence of PEG-400 under heating condition afforded the target products isoxazolyl pyrido[2,3-d]pyrimidines 11 in good to excellent yields. The target compounds 11a-y was also evaluated for their antimicrobial and anti-inflammatory activities. Among the tested compounds, the compounds 11w, 11x, and 11y showed significant antimicrobial activity and potent anti-inflammatory activity as that of standard drugs. The superiority of this method is catalyst free, operational simplicity, environmental safety; metal free, broad substrate scope, easy purification, high yields and PEG-400 can be recovered and reused.

Graphical Abstract

Keywords:

• Anti-inflammatory activity
• antimicrobial activity
• green chemistry
• isoxazolyl pyrido[2,3-d]pyrimidines
• PEG-400

Acknowledgments

Vanaja Rani thanks the Department of Chemistry Koneru Lakshmaiah Education Foundation for providing research facilities. We are grateful to Prof. K. Ravindhranath and Dr. Nagi Reddy Modugu for their valuable support and discussions.

Disclosure statement

No potential conflict of interest was reported by the author(s).