HETEROCYCLES

■ Optimized Synthesis and Solid State Investigations on the Drug Candidate Encenicline Hydrochloride

Gerhard Laus, Sandro Neuner, Ramona Metz, Thomas Müller, Volker Kahlenberg, Thomas Gelbrich, Sven Nerdinger,* Erwin Schreiner, Verena Adamer, Klaus Wurst, and Herwig Schottenberger

*Global Portfolio, Sandoz GmbH, Biochemiestrasse 10, 6250 Kundl, Austria

Abstract

For the production of drug substances a robust, scalable process delivering the active pharmaceutical ingredient (API) in excellent chemical and polymorphic purity is required. For this purpose we developed a novel imidazole-mediated one-pot procedure for the preparation of encenicline hydrochloride monohydrate, which crystallizes directly from the reaction mixture as pure non-hygroscopic polymorph (Form I). Solid state studies revealed a series of additional new physical forms for which crystal structures have been determined by single crystal X-ray diffraction.