School of Pharmaceutical Science, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, China.
Shanxi Key laboratory of Chronic Inflammatory Targeted Drugs, School of Chinese Materia Medica, Shanxi University of Traditional Chinese Medicine, 121 University Street, Jinzhong 030602, China.
Molecules. 2020 Jan 22;25(3):468. doi: 10.3390/molecules25030468.
Based on a foregoing gram-scale laboratory process, an efficient scale-up preparation process of 5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanone (), a new acute pyelonephritis candidate drug, was developed and validated aiming to reduce by-products and achieve better impurity profiles. Meanwhile, the polymorph of and process-related impurities were also investigated. Ultimately, the optimal reaction conditions were verified by evaluating the impurity profiles and their formation during the synthesis. Six process-related impurities were synthesized and identified, being useful for the quality control of . Its finalized preparation process was further validated at 329-410 g scale-up production in 53.4-57.1% overall yield with 99.95-99.98% high-performance liquid chromatography (HPLC) purity, and it is currently viable for commercial production. and were identified as the main single impurities in , with the content controlled to be less than 0.03%.
基于前文的克级实验室工艺，开发并验证了一种 5,2'-二溴-2,4',5'-三羟基二苯甲酮（）的有效放大制备工艺，旨在减少副产物并改善杂质概况。同时，还研究了和工艺相关杂质的多晶型。最终，通过评估合成过程中的杂质概况和它们的形成，验证了最佳反应条件。合成并鉴定了 6 种工艺相关杂质，可用于的质量控制。其最终的制备工艺在 329-410 克放大生产中进一步得到验证，总收率为 53.4-57.1%，高效液相色谱（HPLC）纯度为 99.95-99.98%，目前可用于商业生产。和 被鉴定为 中的主要单一杂质，其含量控制在 0.03%以下。
