Synthesis of Imidazo[1,2-a]pyridine-Fused 1,3-Benzodiazepine Derivatives with Anticancer Activity via a One-Pot Cascade GBB-3CR/Pd(II)-Catalyzed Azide-Isocyanide Coupling/Cyclization Process

Abstract

A new one-pot synthesis of imidazo[1,2-a]pyridine-fused 1,3-benzodiazepine derivatives via a sequential GBB-3CR/ Pd(II)-catalyzed azide-isocyanide coupling/cyclization process was developed. The Groebke−Blackburn−Bienayméthreecomponent reactions (GBB-3CR) of 2-aminopyridine, 2-azidobenzaldehydes, and isocyanides in the presence of a catalytic amount of p-toluenesulfonic acid gave azide intermediates without separation. The reaction was followed by using another molecule of isocyanides to produce imidazo[1,2-a]pyridine-fused 1,3-benzodiazepine derivatives in good yields by the Pd(II)-catalyzed azideisocyanide coupling/cyclization reaction. The synthetic approach produces novel nitrogen-fused polycyclic heterocycles under mild reaction conditions. The preliminary biological evaluation demonstrated that compound 6a inhibited glioma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.

One-Step Construction of 1,3,4-Oxadiazoles with Anticancer Activity from Tertiary Amines via a Sequential Copper(I)-Catalyzed Oxidative Ugi/aza-Wittig Reaction

“…However, to the best of our knowledge, the metal-catalyzed C(sp 3 )-H bond functionalization of tertiary amines with one-step construction of heterocyclic skeleton has not been reported. Owing to our continuing interest in the synthesis of heterocycle by employing domino IMCRs [43][44][45][46][47][48], we wish to develop a novel one-step construction of 1,3,4-oxadiazoles using the copper-catalyzed oxidative Ugi/aza-Wittig reaction (Scheme 1, Equation ( 4)). In contrast to traditional organic synthesis, the process of functionalizing C(sp 3 )-H bonds through C-H bond activation has garnered considerable attention [20].…”

Synthesis of Triazolo[4′,5′:4,5]furo[2,3-c]pyridine via Post Modification of an Unusual Groebke–Blackburn–Bienaymé Multicomponent Reaction

“…Recently, we demonstrated an undergraduate laboratory experiment wherein GBB-MCR-derived products were synthesized via in situ generated isocyanides from N -formylamines . The diverse fused heterocycles generated via GBB reaction include bicyclic imidazo­[1,2- a ]­pyridine, imidazo­[1,2- a ]­pyrimidine, imidazo­[1,2- a ]­pyrazine, imidazo­[2,1- b ]­thiazole, imidazo­[2,1- b ]­[1,3,4]­thiadiazole, imidazo­[1,2- b ]­[1,2,4]­triazole, imidazo­[1,2- b ]­pyrazol, and imidazo­[2,1- b ]­oxazole. − Various polycyclic scaffolds (1–11, Figure ) are also synthesized via post modification of the GBB-derived products. , Recently, we demonstrated that the one-pot-derived GBB products can be elaborated to fused polycyclic heterocycles (12–14) involving Pictet–Spengler cyclization (Figure ). …”