Leveraging Synergistic Solubility in the Development of a Direct Isolation Process for Nemtabrutinib

• DOI: 10.1021/acs.oprd.2c00391
• Publication Date: 2023-03-10T06:46:01Z
• Authors: Yonggang Chen; Luca Iuzzolino; Samantha A. Burgess; Cheol K. Chung; James Corry; Morgan Crawford; Richard Desmond; Erik Guetschow; Clara Hartmanshenn; Nadine Kuhl; Zhu Liu; Hanlin Luo; Alison C. McQuilken; Justin A. Newman; Hong Ren; David A. Thaisriv...; Zhixun Wang; Eric Sirota
• Keywords: Process development; Robustness; Manufacturing process

We report the process development for active pharmaceutical ingredient (API) step of commercial manufacturing route to nemtabrutinib (MK-1026), a reversible Bruton’s Tyrosine Kinase (BTK) inhibitor currently under investigation treatment several hematological malignancies. Significant improvements on efficiency were achieved by direct isolation leveraging optimal reaction conditions and synergistic API solubility in an ethanol/water system. In combination with additional robustness impurity control, efficient, practical, scalable synthesis was developed.