MCC/SNAr methodology. Part 2: Novel three-step solution phase access to libraries of benzodiazepines
This letter reveals the novel solution-phase syntheses of arrays of biologically relevant benzodiazepines 1, via multi-component condensation (MCC)/SNAr methodology.
Section snippets
Acknowledgments
We would like to thank Adrian Smith and Andrew Tasker for proof-reading this document.
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Multicomponent reactions as a potent tool for the synthesis of benzodiazepines
2021, Organic and Biomolecular ChemistrySynthesis of various N-heterocycles using the four-component Ugi reaction
2020, Advances in Heterocyclic ChemistryCitation Excerpt :Among different strategies for the design of structurally diverse complex molecules (1994MI115, 01PAC187, 02MI306) and combinatorial libraries of heterocyclic compounds using IMCR (1996ACR123, 01MI1, 03MI51, 03MI469, 1999SL366, 00MI318, 11AGE6234), U-4CR/posttransformation has been found as a fruitful and promising approach for the synthesis of a broad range of novel heterocyclic systems, especially those, which could not be easily provided by other synthetic routes. For example, linear dipeptides, which are produced by U-4CR, can be easily subjected to several post-Ugi transformations such as cycloaddition (03OL1047, 03TL7655, 04JOC1207, 04TL3421, 04TL5987, 04TL8439, 05MI958, 05T11511, 07OL1299, 07OL5119, 09TL5773), Pictet–Spengler reaction (09JOC6895, 10JCS(CC)7706, 18MI943), Mitsunobu reaction (06MI4236, 11EJO100, 18AOC4464), ring-closure metathesis (04TL3421, 06OL4145), SN2 reaction (01TL2727, 04TL6421, 06T6774, 08JOC1608), SNAr reaction (03TL1947, 06SL2099), and Rap-Stoermer reaction (14SL2019) to furnish the corresponding heterocyclic systems. The literature contains two useful review articles which offer extensive collection plethora of post-Ugi transformations including Ugi/deprotection/cyclization (UDC), cycloadditions, macrolactonizations, radical cyclizations, acid–base-catalyzed cyclizations, ring closing metathesis, SNAr and SN2 reactions, aryl couplings, etc. (09MI195, 14MI544).
Convenient two-step synthesis of highly functionalized benzo-fused 1,4-diazepin-3-ones and 1,5-diazocin-4-ones by sequential Ugi and intramolecular S<inf>N</inf>Ar reactions
2017, TetrahedronCitation Excerpt :Among them, the Ugi-deprotection-cyclization (UDC) strategy is the most commonly used and was shown to be very powerful to prepare benzodiazepinone derivatives.35–38,41–44,49–66 To perform the cyclization step, several strategies including ester or amide aminolysis,9,10,49–58 imine formation,55,59 aromatic nucleophilic substitution (SNAr),60,61 Staudinger/aza-Wittig,62–65 aza-Michael,33 and Mitsunobu66 reactions have been used. However, because they often involve modified or hardly accessible building blocks and/or Boc protecting group removal prior to cyclization, most reported UDC methodologies generate limited functional diversity on benzodiazepinone scaffolds.