Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

25CN-NBOH is a selective serotonin 2A receptor agonist used extensively as a tool compound in preclinical research. Herein, we perform an in-depth characterization of 25CN-NBOH and report key physicochemical properties in the solid state as well as in the solution state, namely stability, ionization, solubility, partition coefficient, and membrane permeability. We show that the hydrochloride salt is a stable and well-defined crystalline compound that is also stable in aqueous solutions at room temperature. Furthermore, we show that an intramolecular hydrogen bond is present in solution, which presumably is a key contributor to the high membrane permeability. Collectively, this physical-chemical profiling of 25CN-NBOH provides guidance to researchers with respect to the physiochemical properties and handling of the compound in various research scenarios.