Large-Scale Synthesis of LPA1-Receptor Antagonist ACT-1016-0707

The development and execution of the large-scale synthesis of LPA1-antagonist ACT-1016-0707 is described. Key developments were an improved nitrile hydrolysis, a high-yielding, safe, and easy-to-perform amide coupling, and the isolation and purification of several, previously oily intermediates as crystalline solids. The yield of the longest linear synthesis sequence of nine steps was 34% on a 450 g scale with respect to the final product.