A Scalable Synthesis of CE-157119 HCl Salt, an SRI/5-HT2A Antagonist

A scalable synthesis of CE-157119 HCl salt (1), an SRI/5-HT2A antagonist, was developed via the regioselective SNAr etherification between a phenol and an N-methylamide. This early development route shortened the original 5-step synthesis to three steps, eliminated all chromatography and increased the overall yield from 15% to 34%. The process was implemented for API manufacture from 100-g scale to multikilogram scale.