Multicapillary Flow Reactor: Synthesis of 1,2,5-Thiadiazepane 1,1-Dioxide Library Utilizing One-Pot Elimination and Inter-/Intramolecular Double aza-Michael Addition Via Microwave-Assisted, Continuous-Flow Organic Synthesis (MACOS).
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.
Department of Chemistry, York University, 4700 Keele Street, Toronto ON, M3J 1P3, Canada ; Center for Chemical Methodologies and Library Development at the University of Kansas (KU-CMLD), 2034 Becker Drive, Delbert M. Shankel Structural Biology Center, Lawrence, KS 66047-3761, USA.
Farman
F
Ullah
Qin
Q
Zang
Salim
S
Javed
Aihua
A
Zhou
Christopher A
CA
Knudtson
Danse
D
Bi
Paul R
PR
Hanson
Michael G
MG
Organ
1,2,5-thiadiazepane 1,1-dioxide library; MACOS; double aza-Michael; sultams