Leveraging Synergistic Solubility in the Development of a Direct Isolation Process for Nemtabrutinib,Organic Process Research & Development

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Leveraging Synergistic Solubility in the Development of a Direct Isolation Process for Nemtabrutinib
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2023-03-09 , DOI: 10.1021/acs.oprd.2c00391
Yonggang Chen ₁ , Luca Iuzzolino ₂ , Samantha A. Burgess ₃ , Cheol K. Chung ₁ , James Corry ₁ , Morgan Crawford ₁ , Richard Desmond ₁ , Erik Guetschow ₃ , Clara Hartmanshenn ₁ , Nadine Kuhl ₁ , Zhu Liu ₃ , Hanlin Luo ₃ , Alison C. McQuilken ₃ , Justin A. Newman ₃ , Hong Ren ₁ , David A. Thaisrivongs ₁ , Zhixun Wang ₁ , Eric Sirota ₁

Affiliation

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

中文翻译：

利用协同溶解度开发 Nemtabrutinib 的直接分离工艺

我们报告了 nemtabrutinib (MK-1026) 商业生产路线中活性药物成分 (API) 步骤的工艺开发，nemtabrutinib (MK-1026) 是一种可逆的布鲁顿氏酪氨酸激酶 (BTK) 抑制剂，目前正在研究用于治疗多种血液恶性肿瘤。通过利用乙醇/水系统中的最佳反应条件和协同 API 溶解度的直接分离过程，显着提高了工艺效率。结合对杂质控制的额外稳健性改进，开发了一种高效、实用且可扩展的 nemtabrutinib 合成。

更新日期：2023-03-09

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