In this work, the nucleobase unit of the antiviral drug remdesivir, 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine, was synthesized through five-step continuous flow. By adapting batch synthetic chemistry, 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine was successfully produced through sequential flow operations from the widely available and inexpensive starting material pyrrole. Under optimal flow conditions, 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine was obtained in 14.1% isolated yield in a total residence time of 79 min with a throughput of 2.96 g·h⁻¹. The total residence time was significantly shorter than the total time consumed in batch procedures (> 26.5 h). In flow, the highly exothermic Vilsmeier–Haack and N-amination reactions involving hazardous and unstable intermediates, oxidative liquid–liquid biphasic transformation, and a bromination reaction requiring strict cryogenic conditions are favorably facilitated. The salient feature of this synthesis is that the workup procedures are fully integrated into the reaction sequences by deploying dedicated equipment and separation units, thus forming a streamlined continuous-flow system that maximizes the overall process efficiency. This method represents a greener and more sustainable process to prepare this nucleobase unit with high efficiency and safety.

在这项工作中，抗病毒药物瑞德西韦的核碱基单元 7-溴吡咯并[2,1- f ][1,2,4]三嗪-4-胺是通过五步连续流合成的。通过采用间歇合成化学，7-溴吡咯并[2,1- f ][1,2,4]三嗪-4-胺通过广泛可用且廉价的原料吡咯的连续流动操作成功生产。在最佳流动条件下，7-溴吡咯并[2,1- f ][1,2,4]三嗪-4-胺的分离产率为 14.1%，总停留时间为 79 分钟，通量为 2.96 g·h ⁻¹. 总停留时间明显短于批处理过程中消耗的总时间（> 26.5 小时）。在流动中，涉及危险和不稳定中间体的高放热 Vilsmeier-Haack 和 N-胺化反应、氧化液-液双相转化以及需要严格低温条件的溴化反应得到了有利的促进。该合成的显着特点是通过部署专用设备和分离单元将后处理程序完全集成到反应序列中，从而形成流线型的连续流系统，最大限度地提高整体工艺效率。这种方法代表了一种更绿色、更可持续的过程，可以高效、安全地制备这种核碱基单元。