奥希替尼及其甲磺酸盐的合成及光稳定性

在文献综述的基础上,以3-(2-氯-4-吡啶基)-1-甲基吲哚为起始原料,经过亲核取代、还原、酰胺化和质子化成盐等反应,成功合成出Osimertinib及其甲磺酸盐。在不同光照条件下(黑暗、日光、荧光灯、254nm紫外灯和410nm紫外灯),采用高效液相色谱法对Osimertinib及其甲磺酸盐的甲醇溶液进行监测,研究Osimertinib及其甲磺酸盐的光稳定性。结果表明,Osimertinib原料药具有一定的光稳定性,Osimertinib甲磺酸盐的光稳定性较差,易发生分解反应。因此,Osimertinib甲磺酸盐应当避光保存,以延长其稳定性。通过对奥希替尼(Osimertinib)及其甲磺酸盐的合成和光稳定性的研究工作,为Osimertinib药物研发和生产过程中的质量控制提供实验基础。

Synthesis and photostability of Osimertinib and its mesylate

Based on the literature review, Osimertinib and its mesylate were successfully synthesized through nucleophilic substitution, reduction, acylation, and protonation reactions with the 3-(2-chloro-4-pyridinyl)-1-methylindole as raw material. The photostability of Osimertinib and its mesylate in the methanol solution was studied in by high-performance liquid chromatography under different light conditions (darkness, sunlight, fluorescent lamp, 254 nm UV lamp, and 410 nm UV lamp). The results showed that Osimertinib had a certain photostability, while the Osimertinib mesylate was poor photostability and prone to decomposition. Therefore, Osimertinib mesylate should be stored away from light to prolong its stability. All the results on the synthesis and photostability of Osimertinib and its mesylate, providing experimental basis for the quality control in the development and production process of Osimertinib.