Development Of An Efficient Asymmetric Synthesis Of The Chiral Quaternary 5-Lipoxygenase Activating Protein Inhibitor

The rapid pace of the development program along the structurally complex 5-lipoxygenase activating protein (FLAP) inhibitor required a dual strategic approach within process development. In order to advance the program forward, the Discovery synthesis was rendered safe and scalable while eliminating the non-scalable chromatographic chiral separation. This approach allowed the advancement of the target while offering the necessary development time to discover an efficient asymmetric process for the synthesis of the challenging drug target. Multiple approaches were explored experimentally for an asymmetric synthesis; the ultimate route was derived from a dual boronate rearrangement process that was rendered robust and efficient for large-scale operations.