PEG-400 mediated an efficient eco-friendly synthesis of new isoxazolyl pyrido[2,3-d]pyrimidines and their anti-inflammatory and analgesic activity

Abstract

Polyethylene glycol-400 (PEG-400) has been developed as an efficient and eco-friendly reaction medium for the synthesis of new isoxazolyl pyrido[2,3-d]pyrimidine derivatives 11 from isoxazolyl cyanoacetamide synthon 7. Compound 7 was employed with various aromatic aldehydes 8 and malononitrile 9 in the presence of triethylamine (Et₃N) to afford the corresponding (E)-6-amino-1-(3-methyl-5-styrylisoxazol-4-yl)-2-oxo-4-phenyl-1,2-dihydro- pyridine-3,5-dicarbonitrile 10 at room temperature by using PEG-400 as a solvent medium as well as catalyst. The intermediate 10 on treatment with thiourea in the presence of PEG-400 at 90 °C to give the target compounds isoxazolyl pyrido[2,3-d]pyrimidines 11 in good to excellent yields. The newly synthesized compounds 10 and 11 were characterized by IR, ¹H NMR, ¹³C NMR, and HRMS analysis. The target compounds 11a-x was screened for their anti-inflammatory and analgesic activities. Among the tested compounds, the compounds 11s, 11t, 11u, 11v, 11w, and 11x showed significant anti-inflammatory and potent analgesic activities as that of reference drugs. The advantages of this protocol are operational simplicity, catalyst free, environmental safety, wide substrate scope, good yields, and PEG-400 can be recovered and reused. Most significant of all, this protocol is green.

Graphical Abstract

Keywords:

• Isoxazolyl pyrido[23-d]pyrimidines
• anti-inflammatory activity
• analgesic activity
• green chemistry
• PEG-400

Acknowledgments

DS thanks the Department of Chemistry Koneru Lakshmaiah Education Foundation and Mylan Laboratories for providing research facilities. We are grateful to Dr. Lakshmana Rao and Dr. NAGI REDDY for their helpful discussions.

Disclosure statement

The authors declare no conflict of interest.