Crystal structure of a 1:1 co-crystal of quabodepistat (OPC-167832) with 2,5-di-hydroxy-benzoic acid using microcrystal electron diffraction.

Abstract

Quabodepistat [(5-{[(3R,4R)-1-(4-chloro-2,6-di-fluoro-phen-yl)-3,4-di-hydroxy-piperidin-4-yl]meth-oxy}-8-fluoro-3,4-di-hydro-quinolin-2(1H)-one); C21H20ClF3N2O4] and 2,5-di-hydroxy-benzoic acid (2,5DHBA; C7H6O4) were successfully co-crystallized. Given the small size of the crystals (1 × 0.2 × 0.2 µm) the structure was solved via microcrystal electron diffraction (MicroED). The C-O and C=O bond-length ratio of the carb-oxy-lic group in 2,5DHBA is 1.08 (1.34 Å/1.24 Å), suggesting that 2,5DHBA remains protonated. Therefore, the material is a co-crystal rather than a salt. The amide group of quabodepistat participates in a cyclic hydrogen bond with the carb-oxy-lic group of the 2,5DHBA. Additional hydrogen bonds involving the quabodepistat amide and hydroxyl groups result in a three-dimensional network.