Solid-form screening and absolute structure determination of antithrombotic diastereomers S007–867 and S007–1175

Abstract

Two novel anti-thrombotic diastereomers S007–867 and S007–1175 had been recently identified by CSIR-CDRI. We performed extensive experimental solid-form screening studies on the most active diastereomer S007–867, which led to the identification of several new solid-forms (two polymorphs, a benzene solvate, and two plausible multi-component forms). Whereas, a single crystal form is identified for the less active diastereomer S007–1175. All newly identified crystalline forms of the two diastereomers were thoroughly characterized with the help of differential scanning calorimetry and X-ray diffraction. We also evaluated the contributions made by various atom···atom contacts in their crystal structures with the help of Hirshfeld surface analysis. Physicochemical property evaluation of the solid-forms of S007–867 reveals ∼2-fold enhancement in aqueous solubility for the 1:2 succinic acid eutectic mixture. We also report the full absolute structure determination of both diastereomers along with the chiral precursor, tert‑butyl N-(3(S)-piperidyl methyl)carbamate used in the synthesis of S007–867 from the single-crystal X-ray diffraction.