Improved Synthesis of the Antitubercular Agent SQ109

We present here an improved procedure for the preparation of the promising antitubercular drug SQ109 that is currently in phase lb/III of clinical trials against Mycobacterium tuberculosis. We investigated and tested the literature synthetic procedure that enables the development of structure-activity relationships and report the observed inconsistencies as well as presenting improvements or novelties for the more efficient preparation of SQ109. Most significantly we applied a novel reduction step of the aminoamide precursor using Me3SiCl/ LiAlH4 under mild conditions. These findings are important for research groups investigating the efficacy of this drug and analogues in academia and industry.