Continuous Flow Conditions for High Temperature Formation of a Benzodioxan Pharmaceutical Intermediate: Rapid Scaleup for Early Phase Material Delivery
Contributor(s):: Li, Pengbin, Yang, Shaohui, Zhu, Ruiheng, Sun, Baoquan, Li, Zhongbo, Huang, Ping, Buser, Jonas Y., Minguez, Jose Miguel, Ryan, Sarah J.
We have developed a continuous flow method to enable rapid scaleup of an enantioenriched benzodioxan intermediate. We propose that the reaction proceeds through an intramolecular SNAr cyclization. Interestingly, traditional SNAr conditions resulted in impurity formation. When the starting...
Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions
Contributor(s):: Cole, Kevin, Groh, Jennifer McClary, Johnson, Martin D., Burcham, Christopher L., Campbell, Bradley M., Diseroad, William D., Heller, Michael R., Howell, John R., Kallman, Neil J., Koenig, Thomas M., May, Scott A., Miller, Richard D., Mitchell, David, Myers, David P., Myers, Steven S., Phillips, Joseph L., Polster, Christopher S., White, Timothy D., Cashman, Jim, Hurley, Declan, Moylan, Robert, Sheehan, Paul, Spencer, Richard D., Desmond, Kenneth, Desmond, Paul., Gowran, Olivia
Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process...