A new approach to monoprotected 1, 4-benzodiazepines via a one-pot N-deprotection/reductive cyclization procedure. Issue 13 (31st March 2016)

• Record Type: Journal Article
• Authors: Popp, Tobias Alexander; Uhl, Edgar; Ong, Duc Nghia; Dittrich, Sebastian; Bracher, Franz
• Is Part Of: Tetrahedron. Volume 72:Issue 13(2016)
• Page Start: 1668
• Page End: 1674
• Publication Date: 2016-03-31
• Subjects: Benzodiazepines -- Cyclization -- Triethylsilane -- Deprotection -- One-pot reaction; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2016.02.019
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: A novel approach to 2, 3, 4, 5-tetrahydro-1 H -1, 4-benzodiazepines starting from N -Boc-protected 2-aminobenzyl alcohols and N -nosyl-protected 2-aminoacetaldehyde dimethyl acetal is presented here. After connection of both building blocks under Mitsunobu conditions, a one-pot cyclization is accomplished with triethylsilane and trifluoroacetic acid. This conversion involves Boc deprotection and an intramolecular reductive N-alkylation. A consecutive methylation at N-1 can be accomplished by adding 1, 3, 5-trioxane to the reaction mixture. The resulting N4-monoprotected 1, 4-benzodiazepines are versatile building blocks for the synthesis of variously substituted drug candidates. Graphical abstract: