Improved Synthesis of the Antitubercular Agent SQ109

We presented here an improved procedure for the preparation of the promising anti-tubercular drug SQ109 (10) which is currently in phase Ib/III of clinical trials against Mycobacterium tuberculosis. We investigated and tested the literature synthetic procedure that enables the development of structure-activity relationships and reported the observed inconsistencies as well as presented improvements or novelties for the more efficient preparation of SQ109 (10). Most significantly we applied a novel reduction step of the aminoamide precursor using Me3SiCl/LiAlH4 under mild conditions in the synthesis of SQ109 (10). These findings are important for research groups investigating the efficacy of this drug and analogues in academia and industry.