Drug resistance to tuberculosis is still one of the major challenges worldwide. Clofazimine, which belongs to the riminophenazine (antibiotic) class, is still one of the active drugs that are efficient against drug-resistant Mycobacterium tuberculosis. Apart from this, it is also a WHO-approved drug for the treatment of leprosy and, at present, is under phase 2 clinical trial for its activity against the SARS-CoV-2 virus. Owing to its vast importance in clinical research, we have developed a semicontinuous flow-mediated synthesis of Clofazimine using readily available p-chloroaniline and 1-fluoro-2-nitrobenzene. The target drug molecule was obtained from four consecutive chemical transformations with nominal residence time, improved purity, and yields when compared to the batch process. Moreover, the first two steps were also successfully telescoped under the optimized reaction conditions.

中文翻译：

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连续流合成多重耐药药物氯法齐明


结核病耐药性仍然是世界范围内的主要挑战之一。氯法齐明属于 riminophenazine（抗生素）类，仍然是有效对抗耐药结核分枝杆菌的活性药物之一。除此之外，它还是 WHO 批准的用于治疗麻风病的药物，目前正因其对 SARS-CoV-2 病毒的活性而处于 2 期临床试验中。由于其在临床研究中的重要性，我们使用现成的对氯苯胺和 1-氟-2-硝基苯开发了一种半连续流介导的氯法齐明合成方法。目标药物分子是通过 4 次连续的化学转化获得的，与批处理工艺相比，具有标称停留时间、更高的纯度和产率。此外，前两个步骤也在优化的反应条件下成功进行了望远镜。