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Process development of clinical anti-HBV drug Y101: identification and synthesis of novel impurities

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Abstract

Nine novel process impurities of N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol (Y101) observed during the laboratory optimization and later during its bulk synthesis are described in this article. The impurities were monitored by HPLC, and their structures were tentatively assigned on the basis of fragmentation patterns in LC−MS/MS and NMR spectroscopies. All of the impurities were synthesized, and their assigned constitutions were confirmed by co-injection in HPLC. In addition to the formation, synthesis, and characterization, the strategy for minimizing these impurities to a level accepted by the International Conference on Harmonisation (ICH) was also described.

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Acknowledgments

This work was supported by grants from the Ministry of Science and Technology of China (No. 2011ZX09102-009-2), the National Natural Science Fund of China (NSFC No. 30760292), and the Science and Technology Department of Guizhou Province (No. QKHZYZ [2012] 5054).

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Correspondence to Bixue Xu or Guangyi Liang.

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Hu, Z., Liao, H., An, Q. et al. Process development of clinical anti-HBV drug Y101: identification and synthesis of novel impurities. Res Chem Intermed 42, 2577–2595 (2016). https://doi.org/10.1007/s11164-015-2169-0

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