Crystal structure of osimertinib mesylate Form B (Tagrisso), (C28H34N7O2)(CH3O3S)

• Published in: Powder diffraction Vol. 36; no. 4; pp. 282 - 290
• Main Authors: Kaduk, James A., Boaz, Nicholas C., Markun, Emma L., Gindhart, Amy M., Blanton, Thomas N.
• Format: Journal Article
• Language: English
• Published: New York, USA Cambridge University Press 01.12.2021
• Subjects: Anions; Cations; Crystal structure; Diffraction patterns; Hydrogen bonds; New Diffraction Data; Nitrogen; Pharmaceuticals; Synchrotron radiation; Synchrotrons; X ray powder diffraction; United States > US; Rietveld refinement; Tagrisso; osimertinib mesylate; density functional theory; powder diffraction
• ISSN: 0885-7156; 1945-7413
• DOI: 10.1017/S0885715621000555

The crystal structure of osimertinib mesylate Form B has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional techniques. Osimertinib mesylate Form B crystallizes in space group P-1 (#2) with a = 11.42912(17), b = 11.72274(24), c = 13.32213(22) Å, α = 69.0265(5), β = 74.5914(4), γ = 66.4007(4)°, V = 1511.557(12) Å3, and Z = 2. The crystal structure is characterized by alternating layers of cation–anion and parallel stacking interactions parallel to the ab-planes. The cation is protonated at the nitrogen atom of the dimethylamino group, which forms a strong hydrogen bond between the cation and the anion. That hydrogen atom also participates in a weaker intramolecular hydrogen bond to an amino nitrogen. There are two additional N–H⋅⋅⋅O hydrogen bonds between the cation and the anion. Several C–H⋅⋅⋅O hydrogen bonds also link the cations and anions. The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™.