Development of a Practical and Scalable Process for Lifitegrast

A practical and scalable manufacturing process for the anti-inflammatory drug lifitegrast, approved by the FDA in 2016 for the treatment of dry eye disease, was developed from commercially available starting materials. Key features of the approach are protecting-group-free synthesis that led to inhibition of racemization of lifitegrast during amide coupling and a process to remove oligomerization impurities and the undesired optical isomer of lifitegrast formed due to the presence of the corresponding optical isomer from the chiral starting material. Lifitegrast manufactured from this route complied with the quality guidelines as per the International Council of Harmonization (ICH).