Alternative Synthesis of 5‐(1H‐Pyrazol‐4‐yl)‐2‐{6‐[(2,2,6,6‐tetramethylpiperidin‐4‐yl)oxy]pyridazin‐3‐yl}phenol.

A scalable and environmentally benign route to the free base of branaplam, a small molecule splicing modulator, was identified and developed. This alternative approach circumvented the inherent risk of dioxin formation associated with ortho‐halo phenol derivatives present in the previous route. A Friedel–Crafts approach provided a reliable access to the key intermediate, subsequently followed by a Suzuki–Miyaura cross‐coupling. Multiple process aspects of the synthetic approach were evaluated, and a robust process for its large‐scale synthesis was developed and successfully demonstrated. [ABSTRACT FROM AUTHOR]