Development of a Scalable Synthesis of a Drug-Linker for ABBV-3373

A scalable process to produce glucocorticoid-bearing drug-linker 1, utilized in the conjugation with the monoclonal antibody (mAb) adalimumab, has been developed. The route improves upon the first-generation approach through a more convergent assembly of the linker and warhead. Optimization and insights into the key transformations are discussed, including a challenging acetonide deprotection, acetal formation under strongly acidic conditions, and amide coupling and purification.