Scalable and Cost-Effective Synthesis of a Linker for Bioconjugation with a Peptide and a Monoclonal Antibody

An efficient, scalable, and cost-effective synthesis of a linker employed in a bioconjugation process with a peptide and a monoclonal antibody is presented. Several routes were investigated that resulted in the identification of a short synthesis to a key acid intermediate from inexpensive and readily available starting materials. The final coupling of this acid with an aniline to afford the desired linker has been optimized to produce multi-gram quantities of material for clinical studies. The very limited purifications needed for both intermediates and final product make this route amenable to scale.