A new approach to monoprotected 1,4-benzodiazepines via a one-pot N-deprotection/reductive cyclization procedure

作者：Popp Tobias Alexander; Uhl Edgar; Duc Nghia Ong; Dittrich Sebastian; Bracher Franz

来源：Tetrahedron, 2016, 72(13): 1668-1674.

DOI：10.1016/j.tet.2016.02.019

• Benzodiazepines
• Cyclization
• Triethylsilane
• Deprotection
• One-pot reaction

A novel approach to 2,3,4,5-tetrahydro-1H-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.

• 出版日期2016-3-31