The scarcity of complex intermediates inpharmaceutical research motivates the pursuit of reaction optimizationprotocols on submilligram scales. We report here the development of anautomated flow-based synthesis platform, designed from commercially availablecomponents, that integrates both rapid nanomole-scale reaction screening andmicromole-scale synthesis into a single modular unit. This system was validatedby exploring a diverse range of reaction variables in a Suzuki-Miyaura couplingon nanomole scale at elevated temperatures, generating liquidchromatography–mass spectrometry data points for 5760 reactions at a rate of>1500 reactions per 24 hours. Through multiple injections of the samesegment, the system directly produced micromole quantities of desired material.The optimal conditions were also replicated in traditional flow and batch modeat 50- to 200-milligram scale to provide good to excellent yields.

图1. 流动系统设置和段制备。

图2. 模型Suzuki-Miyaura偶联反应。

图3. 完整的热图可视化。

图4. 模型Suzuki-Miyaura偶联反应的数据分析。

图5. Suzuki-Miyaura偶联反应-成功条件。

图6. 放大验证和PMC优化。

A platform for automated nanomole-scale reaction screening and micromole-scale synthesis in flow