Multicapillary Flow Reactor: Synthesis of 125-Thiadiazepane 11-Dioxide Library Utilizing One-Pot Elimination and Inter-/Intramolecular Double aza-Michael Addition Via Microwave-Assisted Continuous-Flow Organic Synthesis (MACOS)

摘要

A microwave-assisted, continuous-flow organic synthesis (MACOS) protocol for the synthesis of functionalized 1,2,5-thiadiazepane 1,1-dioxide library, utilizing a one-pot elimination and inter-/intramolecular double aza-Michael addition strategy is reported. The optimized protocol in MACOS was utilized for scale-out and further extended for library production using a multicapillary flow reactor. A 50-member library of 1,2,5-thiadiazepane 1,1-dioxides was prepared on a 100- to 300-mg scale with overall yields between 50 and 80% and over 90 % purity determined by proton nuclear magnetic resonance (¹H-NMR) spectroscopy.