Crystal Structure, Stability and Desolvation of the Solvates of Sorafenib Tosylate

In this study, three solvates of sorafenib tosylate were obtained from methanol, ethanol and n-methyl-2-pyrrolidone (NMP) after solvate screening and the e ff ect of solvent on the formation of solvate was analyzed. The solvents with high value of polarity/dipolarity and appropriate hydrogen bond donor/acceptor propensity are more likely to form corresponding solvates. The crystal structures of the solvates were elucidated for the first time by using single crystal X-ray di ff raction data. The analysis results indicate that methanol solvate and ethanol solvate are isostructural and hydrogen bonds could be formed between solvent molecules and sorafenib tosylate molecules. Hirshfeld surface analysis was used to research the interactions in the solvates, and the results reveal that the H center dot center dot center dot H, C center dot center dot center dot H/H center dot center dot center dot CandO center dot center dot center dot H/H center dot center dot center dot Ocontacts play the vital role in molecular packing. In addition, three solvates were characterized by polarized light microscope, powder X-ray di ff raction, thermogravimetric analysis and di ff erential scanning calorimetry. The solvates show di ff erent thermodynamic stability in methanol + NMP and ethanol + NMP mixtures. Furthermore, the desolvation of solvates was studied by hot stage microscope and discussed.