Kilogram-Scale Synthesis and Impurity Profiling of a COPD Candidate LY104: Optimization of Salt Forms for Enhanced Purity and Pharmaceutical Potential

This study describes a synthetic route to access LY104, a structurally novel compound investigated for the treatment of chronic obstructive pulmonary disease (COPD). Our approach to LY104 encompasses (i) a concise and efficient synthetic strategy for this COPD candidate and (ii) a scalable process with structural characterization of related impurities. The synthesis of LY104 was accomplished in four steps, during which three key impurity structures were identified. Through careful optimization of the chemical process, LY104 acetate salt was consistently obtained in a high purity (>99.85%) for pharmacological studies.