Ethylenediamine diacetate-catalyzed three-component reaction for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones and their spirooxindole derivatives

Synthesis, Evaluation and Proposed Binding Pose of Substituted Spiro‐Oxindole Dihydroquinazolinones as IRAP Inhibitors

“…Two and three-component reactions of structurally similar compounds have been published, typically requiring reflux for several hours. [34][35][36][37][38][39] We aimed to improve the synthetic procedures for this type of scaffold and have previously demonstrated that compound 1 can be synthesized alongside a series of analogs in a smooth and scalable way using microwave (MW) heated continuous flow synthesis (1-3, 23, 26-29, 31). [40,41] Here we show that these spiro-compounds can be obtained utilizing MW heated batch chemistry in a rapid and simple way.…”

“…Moreover, despite being more polar (see Table 2), these compounds also lost activity on human IRAP. Introduction of a saturated carbon chain (38) furnished the most active compound in this series so far. Again, since we had seen that the compounds lost activity on human IRAP, we next tried to synthesize more soluble derivatives.…”

Recent Advances in Green Synthesis of 3,3′‐Spirooxindoles via Isatin–based One–pot Multicomponent Cascade Reactions in Aqueous Medium

“…In 2013, Choudhury [43] developed an efficient base-catalyzed synthesis of novel spiro-pyrrolidine-oxindoles derivatives (50) via a regioselective sequential three-component reaction of isatins, malononitrile and thiohydantoin or hydantoin (49) in water solvent (Scheme 12). Due to the obvious advantage of green solvent, easy purification and mild reaction conditions, this method would have a broad application in green synthesis of spirooxindole derivatives.…”

V‐N‐C catalysts anchored to mesoporous Al‐SBA‐15 with tailorable pore sizes for the synthesis of spirooxindole dihydroquinazolinones derivatives

“…To date, many attempts have been devoted to disclose desirable protocols for the synthesis of spirooxindoles. In this line, the utilities of many catalysts, including KAl (SO 4 ) 2 ·12H 2 O (alum), 1‐methylimidazolium hydrogen sulfate, ethylenediamine diacetate and nano CeO 2 , have been evidenced, whereas some of these experimental procedures have obvious negative aspects, such as long reaction times, low yields and harsh reaction conditions. Accordingly, to avoid these limitations, the exploration of an efficient, easily available catalyst with high catalytic activity and short reaction times for the preparation of spirooxindole dihydroquinazolinone is still favored.…”