Preparation and powder X-ray diffraction study of tecovirimat hydrate solid forms

Tecovirimat [ST-246; systematic name: N-(3,5-dioxo-4-azatetracyclo[5.3.2.0²,⁶.0⁸,¹⁰]dodec-11-en-4-yl)-4-(trifluoromethyl)benzamide monohydrate, C₁₉H₁₅F₃N₂O₃] is an essential antiviral drug used against orthopoxviruses, yet its solid-state landscape remains only partially characterized. Here we identify experimental conditions enabling the reproducible crystallization of three hydrated forms reported in the patent literature: two monohydrates (I and III) and one hemihydrate (V). The phase purity of all samples was confirmed by Rietveld refinement of the powder X-ray diffraction patterns. The single-crystal structures of forms I and V were determined for the first time, whereas the structure of monohydrate III was redetermined at 293 K to allow direct comparison under identical conditions.