Crystal Structure of Nilotinib Hydrochloride Monohydrate According to Powder X-Ray Diffraction Data

The crystal structure of nilotinib hydrochloride monohydrate, being an active pharmaceutical substance of the drug Tasigna for chronic myeloid leukemia, is determined by powder X-ray diffraction (XRD) using a synchrotron radiation source of the National Research Center “Kurchatov Institute”. The molecular conformation of the cation in the crystal differs from that in the initial nilotinib molecule and its solvates due to the rotation of substituents about single C–N, C–O, and C–C bonds. In the crystal, the nilotinib molecule is protonated at the nitrogen atom of the imidazolium heterocycle and involved in the N–H…N, N–H…O, and N–H…Cl hydrogen bonds with another cation, water molecule, and anion respectively. The resulting structure is determined with high accuracy. Errors in bond lengths are only slightly worse than those for the structures determined from single crystal XRD data. In addition, one of the best values of the half uncertainty window (HUW) is achieved in the refinement. The importance of this parameter is considered in the article. The structure agrees with the solid-state NMR data. The comparison of the results with the solution NMR spectroscopy data reveals noticeable changes in the nilotinib molecular structure during crystallization.