PEG‐400 Mediated an Efficient Green Synthesis of Isoxazolyl Indole‐3‐Carboxylic Acid Esters via Nentizescu Condensation Reaction and Their Anti‐Inflammatory and Analgesic Activity

Abstract

Polyethylene glycol‐400 (PEG‐400) has been discovered as an efficient and eco‐friendly reaction medium for the synthesis of new isoxazolyl indole‐3‐carboxylic acid esters 11 from 4‐amino‐3‐methyl‐5‐styrylisoxazoles 7. Compounds 7 on treatment with β‐keto ester 8 afforded the corresponding isoxazolylamino‐2‐butenoates 9 at ambient temperature in PEG‐400. The Nentizescu condensation of compounds 9 with 1,4‐benzoquinone 10 to give the title compounds isoxazolyl indole‐3‐craboxylic acid esters 11 under PEG‐400. Structures of compounds 9 and 11 were established on the basis of IR, 1H NMR, 13C NMR and HRMS analysis. All the final compounds 11 a–s were evaluated for their anti‐inflammatory and analgesic activities. Among the compounds tested, the compounds 11 b, 11 g, 11 n, 11 o, 11 p and 11 s exhibited significant anti‐inflammatory and potent analgesic activities as that of standard drugs. The advantages of this protocol are: operational simplicity, environmental safety, broad substrate scope, excellent functional group tolerance, and good yields. The PEG‐400 can be recovered and reused.