Synthesis and Impurity Research of 2-Thioadenosine Monohydrate

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.