Synthesis and Impurity Research of 2-Thioadenosine Monohydrate

Jing-Jing Xiang; Bi-Bo Jiang; Wen-Qing Sun; Fu-Li Zhang; Jun Yu

doi:10.1055/s-0043-1768692

Pharmaceutical Fronts, Inhaltsverzeichnis

CC BY 4.0 · Pharmaceutical Fronts 2023; 05(02): e84-e90
DOI: 10.1055/s-0043-1768692

Original Article

Synthesis and Impurity Research of 2-Thioadenosine Monohydrate

Jing-Jing Xiang^#

¹School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, People's Republic of China

,

Bi-Bo Jiang^#

²Engineering Research Center for Improvement and Industrialization of Pharmaceutical Processes, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China

,

Wen-Qing Sun

³Shandong Ruizhi Pharmaceutical Technology Co., Ltd., Heze, People's Republic of China

,

Fu-Li Zhang

¹School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, People's Republic of China

²Engineering Research Center for Improvement and Industrialization of Pharmaceutical Processes, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China

,

Jun Yu

²Engineering Research Center for Improvement and Industrialization of Pharmaceutical Processes, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China

› Institutsangaben

Abstract

2-Thioadenosine monohydrate (1) is a vital intermediate in the synthesis of cangrelor. However, its industrial-scale preparation process and the analysis of the impurities formed during this process remained largely unknown. Herein, cangrelor was synthesized from oxidate adenosine, and the key step involved in the synthesis of compound 1 from intermediate 5. The effects of key synthesis parameters that influenced the reaction, including reaction temperature and time, were discussed. Moreover, four process-related impurities were purified, synthesized, and identified via nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. The process can be utilized to produce 1 on a kilogram scale, with a high-performance liquid chromatography purity of 98.0%. The study sheds light on and helps drug manufacturers further understand the formation process of impurities in the preparation of cangrelor.

Keywords

cangrelor - 2-thioadenosine monohydrate - a kilogram scale - impurities

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Referenzen

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