An Efficient One-Pot Strategy for the Synthesis of Triazole-Fused 1,4-Benzodiazepinones from N-Substituted 2-Azidobenzamides

Abstract

A catalyst-free, one-pot strategy for the synthesis of 1,2,3-triazole-fused 1,4-benzodiazepinone derivatives from N-substituted 2-azidobenzamides and propargyl bromide, in the presence of a base, is reported. The products are formed in good to excellent yields via N-alkylation followed by a 1,3-dipolar cycloaddition.

Growing Impact of Intramolecular Click Chemistry in Organic Synthesis

“…[183] Majumdar and co-workers nicely exemplified the intramolecular azide-alkyne cycloaddition of azido-alkyne precursor 251, obtained from propargylation of N-substituted-2-azidobenzamides 249 under basic condition in DMF at 70 °C to furnish good-to-excellent yield of the respective 1,2,3-triazolefused 1,4-benzodiazepinone 252 as the sole product (Scheme 58). [184] Avoid of use of catalyst and ease of isolation of the products, high reaction yield and mild conditions are the notable advantage of this protocol.…”

“…The O-toluidines were converted into their equivalent azides 253 in the first step through diazotization the amino group with NaNO 2 /HCl, followed by substitution with an azide anion from sodium azide. In the following step, benzoyl peroxide and NBS (N-bromosuccinimide) were combined [184] Scheme 59. Intramolecular click inspired synthesis of triazolo[1,5-a] [1,4]benzodiazepines 257 from O-toluidine.…”

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

“…Although derivatives of 1,2,3-triazolobenzodiazepines are less studied as to their 1,2,4-triazole fused analogs, 1,2,3-triazolobenzodiazepinone A ( Figure 2 ) has already reached clinical success in the treatment of CNS disorders [ 6 ]. Preliminary studies of the biological activity of other diversely substituted 1,2,3-triazolobenzodiazepines demonstrate their similar properties with all main categories of 1,2,4-triazolobenzodiazepine-based drugs [ 7 ].…”

Solid‐Phase Synthesis of Trisubstituted Benzo[f][1,2,3]triazolo[1,5‐a][1,4]diazepin‐6(5H)‐ones and Their Sulfonyl Analogues under Mild Reaction Conditions

“…[16] In the case of the catalytic Huisgen reaction leading to triazolobenzodiazepinones, an intramolecular Ugi/azide-alkyne cycloaddition catalysed by copper at room temperature, was reported. [18] The latest contributions from this frequently studied field were introduced in 2013, and dealt with one-pot snthesis [19] or cross-coupling reactions. [18] The latest contributions from this frequently studied field were introduced in 2013, and dealt with one-pot snthesis [19] or cross-coupling reactions.…”

“…[17] Recently, the use of the click reaction has also been described for the synthesis of tetracyclic triazole-fused benzodiazepine derivatives. [18] The latest contributions from this frequently studied field were introduced in 2013, and dealt with one-pot snthesis [19] or cross-coupling reactions. [20,21] In this report, we introduce a new approach based on solid-phase synthesis, suitable for the preparation of target triazolobenzodiazepine derivatives with three sites of diversity.…”