Macozinone: revised synthesis and crystal structure of a promising new drug for treating drug‐sensitive and drug‐resistant tuberculosis

Mycobacterium tuberculosis (Mtb), the principal etiological agent of tuberculosis (TB), infects over one‐quarter of humanity and is now the leading cause of infectious disease mortality by a single pathogen. Macozinone {2‐[4‐(cyclohexylmethyl)piperazin‐1‐yl]‐8‐nitro‐6‐(trifluoromethyl)‐4H‐1,3‐benzothiazin‐4‐one, C₂₀H₂₃F₃N₄O₃S} is a promising new drug for treating drug‐sensitive and drug‐resistant TB that has successfully completed phase I clinical trials. We report the complete spectroscopic and structural characterization by ¹H NMR, ¹³C NMR, HRMS, IR, and X‐ray crystallography. The cyclohexyl moiety is observed to be nearly perpendicular to the core formed by the 1,3‐benzothiazin‐4‐one and piperazine groups. The central piperazine ring adopts a slightly distorted chair conformation caused by sp²‐hybridization of the nitro N atom, which donates into the electron‐deficient 1,3‐benzothiazin‐4‐one group.