Abstract
This paper describes the development of a relatively feasible, economic, and safe method for the multigram-scale synthesis of BIIB068, an efficient reversible BTK inhibitor. The new process is highlighted by an economical construction of a 2-amino-4 substituted pyrimidine employing a simple nucleophilic substitution reaction and a green reduction of the cyano group. The developed process provided an overall yield of 32%, with an HPLC purity of 99%. The structure of BIIB068 was confirmed by MS, IR, 1H-NMR, and 13C-NMR, and the structures of some intermediates were confirmed by MS and 1H-NMR.
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Jia, D., Gu, M., Yu, X. et al. Multigram‑scale synthesis of BTK inhibitor BIIB068. Chem. Pap. 77, 6471–6481 (2023). https://doi.org/10.1007/s11696-023-02951-9
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DOI: https://doi.org/10.1007/s11696-023-02951-9