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Solid-phase synthesis of trisubstituted benzo[1,4]-diazepin-5-one derivatives.

Authors
  • Fülöpová, Veronika1
  • Gucký, Tomáš
  • Grepl, Martin
  • Soural, Miroslav
  • 1 Department of Organic Chemistry, Institute of Molecular and Translational Medicine, Faculty of Science, Palacky University, Olomouc, Czech Republic. , (Czechia)
Type
Published Article
Journal
ACS Combinatorial Science
Publisher
American Chemical Society
Publication Date
Dec 10, 2012
Volume
14
Issue
12
Pages
651–656
Identifiers
DOI: 10.1021/co300124q
PMID: 23145965
Source
Medline
License
Unknown

Abstract

Solid-phase synthesis of 3,4-dihydro-benzo[e][1,4]diazepin-5-ones with three diversity positions is described. Various primary amines were used as the starting material and immobilized on the polystyrene resin equipped with different acid-labile linkers. Polymer-supported amines were converted to α-aminoketones with the use of their sulfonylation with the 4-nitrobenzensulfonylchoride (4-Nos-Cl) and subsequent alkylation with α-bromoketones. After the cleavage of the 4-Nos group, the corresponding α-aminoketones were acylated with various o-nitrobenzoic acids. Reduction of the nitro group followed by spontaneous on-resin ring closure gave the target immobilized benzodiazepines. After acid-mediated cleavage the products were obtained in very good crude purity and satisfactory yields, which makes the developed method applicable for simple library synthesis of the corresponding derivatives in a combinatorial fashion.

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