Improved Manufacturing Route and Polymorphic Control of a Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor ASP3026
| Autor: | Takumi Takahashi, Ryoki Orii, Shun Hirasawa, Minoru Okada, Koji Kobayashi, Kazuyoshi Obitsu, Shigeru Ieda, Yuji Takahama, Norihiro Ueda, Kazuhiro Takeguchi, Takahiro Akiba, Atsushi Ohigashi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
chemistry.chemical_classification
Ketone medicine.drug_class Organic Chemistry Cyanuric chloride Combinatorial chemistry Reductive amination ALK Inhibitor ASP3026 ALK inhibitor chemistry.chemical_compound 1 3 5-Triazine chemistry medicine Moiety Anaplastic lymphoma kinase Physical and Theoretical Chemistry |
| Zdroj: | Organic Process Research & Development. 23:512-523 |
| ISSN: | 1520-586X 1083-6160 |
| Popis: | Our effort toward the process improvement of anaplastic lymphoma kinase (ALK) inhibitor ASP3026 (1) is described. A cost-effective and practical synthesis of 1 was accomplished as a result of the change of starting material from 2,4-dichloro-1,3,5-triazine (6) to cyanuric chloride (9) and late-stage introduction of a highly reactive N-methyl piperazine moiety by reductive amination of intermediate ketone 13. The modified process avoided the challenges with the original synthesis and furnished the several hundred kilograms of high-quality API with high economic efficiency, operability, and reproducibility. Furthermore, a sequence of investigation of polymorphic control in the second-generation synthetic route to obtain the thermodynamically desired, most stable polymorph Form A04 is also discussed. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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