Korenev Georgiy, Gutenev Alexey A, Antipin Fyodor V, Chernyshov Vladimir V, Korobkina Maria P, Nawrozkij Maxim B, Ivanov Roman A
Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy Ave. 1, 354340 Sirius, Krasnodar Region, Russia.
Molecules. 2025 Jul 18;30(14):3011. doi: 10.3390/molecules30143011.
In this study, we report for the first time a brand-new protocol for the multigram-scale synthesis of 5-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylic and 2,8-dimethylimidazo[1,2-]pyridazine-6-carboxylic acids, without the utilization of metal-complex catalysts. The developed technology for the production of the aforementioned acids is of great importance for two reasons. Firstly, these acids serve as intermediates in the synthesis of risdiplam, the first small-molecule drug approved for the treatment of spinal muscular atrophy. Secondly, they themselves are valuable building blocks right from a broader medicinal chemistry perspective. The synthesis of risdiplam was carried out using a modified synthetic protocol, utilizing the acids indicated above as the key intermediates. The protocols presented in this study enable the production of target compounds with high purity and an acceptable yield.
在本研究中，我们首次报道了一种全新的方案，用于多克规模合成5-甲基-6-氧代-1,6-二氢哒嗪-3-羧酸和2,8-二甲基咪唑并[1,2 -]哒嗪-6-羧酸，且不使用金属络合物催化剂。开发上述酸的生产技术具有重要意义，原因有二。其一，这些酸是利司扑兰合成中的中间体，利司扑兰是首个获批用于治疗脊髓性肌萎缩的小分子药物。其二，从更广泛的药物化学角度来看，它们本身就是有价值的构建模块。利司扑兰的合成采用了改进的合成方案，以上述酸作为关键中间体。本研究中提出的方案能够以高纯度和可接受的产率生产目标化合物。
