Evolution of the process strategies to prepare CEP-28122, an anaplastic lymphoma kinase (ALK) inhibitor, is presented. The initial medicinal chemistry route, used for the preparation of key supplies for biological screening, is reviewed. In addition, the process research and development of the final optimized process for manufacture of preclinical and clinical supplies is discussed. Details regarding a blocking group strategy for selective nitration; discovery of a one-pot transfer hydrogenation to effect a reductive amination, nitro group reduction, and dehalogenation; an enzymatic resolution of a critical intermediate; and the discovery of a novel, stable, in situ generated mixed mesylate hydrochloride salt of the API are disclosed.

中文翻译：

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开发和扩大至ALK抑制剂CEP-28122的最佳途径

介绍了制备CEP-28122（一种间变性淋巴瘤激酶（ALK）抑制剂）的工艺策略的演变。审查了最初的药物化学路线，该路线用于制备生物筛选的关键用品。此外，还讨论了用于临床前和临床用品制造的最终优化过程的过程研究和开发。有关选择性硝化的封闭基团策略的详细信息；发现一锅转移加氢以实现还原胺化，硝基还原和脱卤作用；关键中间体的酶促拆分；公开了一种新颖，稳定，原位生成的API混合甲磺酸盐酸盐的发现。