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.

中文翻译：

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ABBV-3373 药物连接体的可扩展合成的开发

已经开发出一种可扩展的工艺来生产带有糖皮质激素的药物接头1 ，用于与单克隆抗体 (mAb) 阿达木单抗缀合。该路线通过更集中的连接器和弹头组装对第一代方法进行了改进。讨论了关键转化的优化和见解，包括具有挑战性的丙酮化物脱保护、强酸性条件下的缩醛形成以及酰胺偶联和纯化。