title: Solid-phase synthesis of trisubstituted benzo[1,4]-diazepin-5-one derivatives.
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.
authors.affiliation: Department of Organic Chemistry, Institute of Molecular and Translational Medicine, Faculty of Science, Palacky University, Olomouc, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Fülöpová
authors.forename: Tomáš
authors.initials: T
authors.lastname: Gucký
authors.forename: Martin
authors.initials: M
authors.lastname: Grepl
authors.forename: Miroslav
authors.initials: M
authors.lastname: Soural
mesh_terms: D000588:Amines / Q000737:chemistry*; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D000588:Amines; D001570:Benzodiazepinones; D007659:Ketones