Evaluation and Development of Practical Routes to an Enantiomerically Pure C2-Symmetric Diamine Building Block

Abstract

Several routes to an enantiomerically pure C2-symmetric diamine were evaluated and modified to scalable methods. A Zn/Me3SiCl-mediated reductive coupling of an imine was found to be superior to the other methods investigated, allowing us to safely prepare the enantiomerically pure diamine also on a large scale. One key step in this method was a highly efficient resolution of a stereoisomeric mixture of the diamine through salt formation with (−)-dibenzoyl-l-tartaric acid. The enantiomerically pure C2-symmetric diamine obtained was further used as a key building block for the synthesis of potent Kv1.5 channel blockers.