Concise Approach toward Tetrazolo[1,5-a][1,4]benzodiazepines via a Novel Multicomponent Isocyanide-Based Condensation

Abstract

A novel and efficient method for the synthesis of heteroannulated [1,4]benzodiazepines via an isocyanide-based multicomponent reaction is reported. The tetrazolo[1,5-a][1,4]benzodiazepines were obtained by a facile azide Ugi five-center four-component reaction (U-5C-4CR) using ketones, sodium azide, ammonium chloride, and corresponding isocyanide. The aforementioned tetrazolodiazepines represent a notable class of compounds with proven platelet aggregation inhibitory and cholecystokinin agonist activities.

A chemoselective Ugi-type reaction in water using TMSCN as a functional isonitrile equivalent: generation of heteroaromatic molecular diversity

“…In addition, these isocyanides are costly, volatile and carry bad odour. 9 As an alternative approach to avoid the use of isocyanide, the Lewis acid-catalyzed Ugi-type reaction of heterocyclic amidine 35 and aldehyde with TMSCN as functional isonitrile equivalent is known (Scheme 1). 10 However, these reactions are non-flexible for versatile reactants and inconvenient.…”

“…Importantly, the method employs water as solvent. 11 The 35 chromatographic separation was not required and the NMR-pure product (4) was obtained by only acid-base work up of crude reaction mixture.…”

Bifunctional building blocks in the Ugi-azide condensation reaction: a general strategy toward exploration of new molecular diversity

“…9 Moreover, an offspring of the Ugi reaction, denoted the Ugi-azide reaction, offers a concise chemical route to 1,5-disubstituted tetrazoles which is initiated with simple replacement of the carboxylic acid with TMSN 3 , delivering 1,5-disubstituted tetrazoles B (Scheme 1). 10 Through use of a variety of assorted reagents and systematically exploring different ring closing possibilities of the Ugi-azide product B, unique scaffolds such as ketopiperazine-tetrazoles, 11 azepine-tetrazoles, 12 benzodiazepine-tetrazoles 13 and quinoxaline-tetrazoles 14 have been successfully generated.…”

Concise One-Pot Preparation of Unique Bis-Pyrrolidinone Tetrazoles

“…Exploration of the Ugi-Azide MCR using a variety of diverse reagents have led to the creation of unique scaffolds as exemplified by ketopiperazine-tetrazoles, 8 azepine-tetrazoles, 11–12 benzodiazepine-tetrazoles, 13 and quinoxaline-tetrazoles. 14 This letter reports the establishment of unique methodology which utilizes keto-esters (methyl levulinate 2 ) along with primary amines, isocyanides, and TMSN 3 to afford novel peptidomimetic-like bis-pyrrolidinone tetrazoles 3 (Scheme 2).…”