X‐Ray Crystal Structures and Complete ¹ H/ ¹³ C NMR Resonance Assignment of the 5‐HT4 Receptor Agonist BIMU8 and its Hydrochloride

Abstract BIMU8 ( N ‐[(1 R ,5 S )‐8‐methyl‐8‐azabicyclo[3.2.1]octan‐3‐yl]‐2‐oxo‐3‐propan‐2‐ylbenzimidazole‐1‐carboxamide) is an agonist of the 5‐HT4 receptor. This receptor is of clinical relevance since it affects several neurological processes, amongst others breathing. In this work, we present the crystal structures of BIMU8, both as a free base and as a hydrochloride salt. Crystals of the free base were grown from ethyl acetate, while slow diffusion of hydrogen chloride vapor into a solution of BIMU8 in ethyl acetate afforded the corresponding hydrochloride crystals. Full sets of 1 H and 13 C NMR spectra of BIMU8 and BIMU8‐HCl were recorded, and complete assignments are reported. Two distinct stereoisomers of the hydrochloride salt were observed in solution by NMR, with the ammonium nitrogen either in exo ‐ or endo ‐configuration, at a ratio of 6:1. In crystals, only the exo ‐form was obtained both for the free base and the hydrochloride salt.