Distinguishing Hydrogen Bonding in Structurally Similar Pharmaceutical Compounds With 1 H‐ 14 N HMQC MAS NMR at 100 kHz

ABSTRACT Solid‐state NMR experiments provide valuable insights into the structure of pharmaceutical compounds, many of which contain nitrogen. Recent literature indicates that the indirect detection of 14 N offers significant advantages for structural analysis, particularly when using two‐dimensional 1 H‐ 14 N HMQC experiments. The advantage of these experiments is that they allow us to rapidly collect information about the hydrogen bonding interaction with a minimal amount of the compound. In our study, we have carried out 1 H‐ 14 N HMQC experiments on structurally similar pharmaceutical compounds sorafenib and regorafenib monohydrate to explore the hydrogen bonding interactions and differentiate different nitrogen signals which are difficult to obtain using 15 N solid‐state NMR experiments on unlabeled compounds. Our findings enable us to distinguish between intramolecular and intermolecular hydrogen bonding interactions and identify different nitrogen atoms in their structures. Thus, our results show that the 1 H‐ 14 N HQMC experiments provide a rapid and effective method for distinguishing different hydrogen bonding interactions.