MCRs reshaped into a switchable microwave-assisted protocol toward 5-aminoimidazoles and dihydrotriazines

Abstract

A tunable microwave-assisted protocol for the synthesis of two biologically relevant families of heterocycles has been designed. Via a simple switch of reaction conditions, the same starting materials can be engaged in either an improved synthesis of the dihydrotriazine scaffold or a novel, first-in-class MCR to render the challenging 5-aminoimidazole nucleus in a single step. An additional first in class MCR is also reported utilizing guanidines to afford 2,5-aminoimidazoles.

A Four‐Component Domino Reaction: An Eco‐Compatible Access to Diversified Imidazo[2,1‐b][1,3]thiazin‐5‐ones

“…Owning to the uniqueness of microwave irradiation in rendering efficiency and selectivity, [12] we decided to explore the optimal conditions under microwave irradiation. Accordingly, the reaction was screened at variouso perating temperatures, that is, 80, 100, 120, 140, and 160 8Cf or 10 min and, to our delight, the desired product 5a was isolated in 50, 62, 71, 88, and 72 %y ields, respectively (Table 1, entries 7-11).…”

Groebke–Blackburn–Bienaymé multicomponent reaction: emerging chemistry for drug discovery

“…Microwave technology has been applied for the rapid synthesis of chemical libraries (including heterocyclic compounds) using MCRs in combinatorial and medicinal chemistry [72,73]. Many examples were presented whereby microwave irradiation was used as an energy-efficient heat source that directly transferred to the molecules of the reaction mixture via dielectric heating.…”

Assembly of 5‐Aminoimidazoles via Palladium‐Catalysed Double Isocyanide Insertion Reaction

“…Among functionally substituted imidazole derivatives, 5‐aminoimidazoles have attracted increased attention owing to their excellent biological activities, such as Hsp90 inhibition, [4] adenosine A 2A receptor antagonism [5] and antiplatelet [6] and antimicrobial activities [7] . Accordingly, great efforts have been devoted to the preparation of 5‐aminoimidazole derivatives [6,8–11] . Multistep cascade reaction (Scheme 1a), [8] microwave‐assisted multicomponent domino cyclisation (Scheme 1b) [9] and Rh‐catalysed transannulation of 1,2,4‐oxadiazoles with 1‐sulfonyl‐1,2,3‐triazoles (Scheme 1c) are notable examples [10] .…”

“…Accordingly, great efforts have been devoted to the preparation of 5‐aminoimidazole derivatives [6,8–11] . Multistep cascade reaction (Scheme 1a), [8] microwave‐assisted multicomponent domino cyclisation (Scheme 1b) [9] and Rh‐catalysed transannulation of 1,2,4‐oxadiazoles with 1‐sulfonyl‐1,2,3‐triazoles (Scheme 1c) are notable examples [10] . Despite this considerable progress, the syntheses of 5‐aminoimidazoles are largely less developed, and they are often restricted by various drawbacks (e. g., tedious synthetic sequences, harsh synthesis conditions, special starting materials and use of expensive catalysts), which seriously limit their further applications.…”