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

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 derivatives11from isoxazolyl cyanoacetamide synthon7. Compound7was employed with various aromatic aldehydes8and malononitrile9in 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-dicarbonitrile10at room temperature by using PEG-400 as a solvent medium as well as catalyst. The intermediate10on treatment with thiourea in the presence of PEG-400 at 90 degrees C to give the target compounds isoxazolyl pyrido[2,3-d]pyrimidines11in good to excellent yields. The newly synthesized compounds10and11were characterized by IR,H-1 NMR,C-13 NMR, and HRMS analysis. The target compounds11a-xwas screened for their anti-inflammatory and analgesic activities. Among the tested compounds, the compounds11s,11t,11u,11v,11w, and11xshowed 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.