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

ACS Comb Sci. 2012 Dec 10;14(12):651-6. doi: 10.1021/co300124q. Epub 2012 Nov 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Benzodiazepinones / chemical synthesis*
  • Benzodiazepinones / chemistry
  • Ketones / chemistry*
  • Molecular Structure

Substances

  • Amines
  • Benzodiazepinones
  • Ketones