An improved process for the synthesis of antidiabetic drug trelagliptin succinate through unprotected (R)-3-aminopiperidine was described. The impurity profile with different conditions of the key substitution was illustrated, and then the best reaction condition was identified. The optimizations also included the bromination of 4-fluoro-2-methylbenzonitrile so that the process became efficient and concise.

中文翻译：

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曲格列汀琥珀酸酯的合成

描述了一种通过未保护的（R）-3-氨基哌啶合成抗糖尿病药物曲拉格列汀琥珀酸酯的改进方法。举例说明了不同键置换条件下的杂质分布，然后确定了最佳反应条件。优化还包括将4-氟-2-甲基苄腈溴化，从而使该过程变得高效而简明。