AbstractA green, effortless, and protective one‐pot three‐component process for the synthesis of derivatives using cycloadition catching azomethineylides in situ created by means of decarboxylative build‐up of sarcosine and isatin has been developed in hexyltriphenylphosphonium bromide (HTPB) as an ionic liquid and recyclable solvent in supreme yield without the use of a catalyst under ultrasonic irradiation. This method offers mild reaction conditions, excellent products yields in shorter reaction times, ease of operation and environmentally friendly process and high ragio and stereoselectivity. The anticancer activity of all new compounds has been investigated against four cell lines. Also, the structures were authenticated by both spectroscopic techniques and signal crystal X‐ray analysis.