Development and Scale-Up of an Optimized Route to the ALK Inhibitor CEP-28122

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...

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Bibliographic Details
Published inOrganic process research & development Vol. 16; no. 1; pp. 148 - 155
Main Authors Allwein, Shawn P, Roemmele, Renee C, Haley, James J, Mowrey, Dale R, Petrillo, Daniel E, Reif, James J, Gingrich, Diane E, Bakale, Roger P
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 20.01.2012
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Applied
Chemistry, Organic
Physical Sciences
Science & Technology
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Summary: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.
ISSN:1083-6160
1520-586X
DOI:10.1021/op200313v