Solid-Phase Synthesis of 3,4,5-Substituted 1,5-Benzodiazepin-2-ones

Citations Over TimeTop 25% of 1999 papers

Abstract

The preparation of 3,4,5-substituted 8-carboxamido-1,5-benzodiazepin-2-ones using a solid-phase synthetic method is described. 4-Fluoro-3-nitrobenzoic acid is tethered to a solid support via the acid group. Aromatic substitution of the aryl fluoride with either an α- or β-substituted β-amino ester is carried out in the presence of DIEA in DMF. The reduction of the aryl nitro group is accomplished in the presence of SnCl2·H2O. Hydrolysis of the ester is carried out in the presence of a heterogeneous mixture of 1 N NaOH/THF (1:1). The resulting aniline acid is cyclized to form the benzodiazepinone skeleton with DIC and HOBt. Selective alkylation at the N-5 position of the benzodiazepinone is accomplished with alkyl halides in the presence of K2CO3 in acetone. The desired products are cleaved from solid supports and obtained in 46−98% isolated yields.

Related Papers

• → Direct Method for Carbon–Carbon Bond Formation: The Functional Group Tolerant Cobalt‐Catalyzed Alkylation of Aryl Halides(2010)126 cited
• → Simple Syntheses of Aryl Alkyl Thioethers and of Aromatic Thiols from Unactivated Aryl Halides and Efficient Methods for Selective Dealkylation of Aryl Alkyl Ethers and Thioethers(1983)125 cited
• → Diisopropylamine as a Coexisting Base for Alkylation of Amines(1980)2 cited
• → Alkylation of -Aryl Amides with Alkyl Halides(2005)
• → ChemInform Abstract: DIORGANOSTANNYLENES. II. PHOTOLYTIC REACTION OF DIPHENYLTIN WITH ALKYL HALIDES(1977)