Synthesis And Properties Of Triazolobenzodiazepine And Imidazole Derivatives

1,4-benzodiazepine derivatives have high drug activity,which especially have a wide range of applications in sedatives,muscle relaxants and anticonvulsants.The compound with 1,2,3-triazole fragment also has good biological activity.More importantly,the spectrum of these therapeutic activities will be improved considerably through the fusion of the 1,4-benzodiazepine scaffold to a triazole ring.Many of the drugs used to treat central nervous system disorder with this composite framework have achieved clinical and commercial success.Multi-substituted imidazole derivatives show the outstanding pharmacological activity in anti-inflammatory,antiviral,antibacterial,allergy,anti-tumor and so on.And it is also extensively applied to organic chemistry,bioscience,material science and other fields.In this paper,triazole fused 1,4-benzodiazepine-5-formamide was synthesized by using continuous Ugi/azide-alkyne cycloaddition reaction.1,2,4,5-tetrasubstituted imidazole-5-formamide was synthesized by cascade acid catalyzed Ugi reaction and Pd(0)catalytic coupling reaction.The details are as follows:1.The synthesis method of triazolobenzodiazepine and multisubstituted imidazole and the latest research progress of conventional Ugi reaction and catalytic Ugi reaction are reviewed.2.The azide intermediate is formed by Ugi-4CR with azidoaniline as the amine component.After the solvent is changed,the mixture is heated under reflux in toluene for several hours to produce[1,2,3]triazolo[1,5-d][1,4]benzodiazepine-5-carboxamide.The synthesis route is as follows:3.The azide intermediate is formed by acid catalytic Ugi-3CR with a-azido cinnamaldehyde as aldehyde component synthesized by cinnamaldehyde.Then,isonitrile and catalytic amount of Pd(PPh3)4 were added to produce directly 1,2,4,5-tetrasubstituted 1H-imidazole-5-carboxamides through tandem Pd(0)-catalyzed coupling/intramolecular nucleophilic addition/isomeration reaction.The synthesis route is as follows:...