Maleate salts of bedaquiline

Bedaquiline is one of two important new drugs for the treatment of drug-resistant tuberculosis (TB). It is marketed in the US as its fumarate salt, but only a few salts of bedaquiline have been structurally described so far. We present here five crystal structures of bedaquilinium maleate {systematic name: [4-(6-bromo-2-meth­oxy­quinolin-3-yl)-3-hy­droxy-3-(naphthalen-1-yl)-4-phenyl­but­yl]di­methyl­aza­nium 3-carb­oxy­prop-2-enoate}, C(32)H(32)BrN(2)O(2) (+)·C(4)H(3)O(4) (−), namely, a hemihydrate, a tetra­hydro­furan (THF) solvate, a mixed acetone/hexane solvate, an ethyl acetate solvate, and a solvate-free structure obtained from the acetone/hexane solvate by in situ single-crystal-to-single-crystal desolvation. All salts exhibit a 1:1 cation-to-anion ratio, with the anion present as monoanionic hydro­maleate and a singly protonated bedaquilinium cation. The maleate exhibits the strong intra­molecular hydrogen bond typical for cis-di­carb­oxy­lic acid anions. The conformations of the cations and packing inter­actions in the maleate salts are compared to those of free base bedaquiline and other bedaquilinium salts.