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Development of a concise, scalable synthesis of a CCR1 antagonist utilizing a continuous flow Curtius rearrangement
24 Apr 2024 | Contributor(s):: Marsini, Maurice A., Buono, Frederic G., Lorenz, Jon C., Yang, Bing-Shiou, Reeves, Jonathan T., Sidhu, Kanwar, Sarvestani, Max, Tan, Zhulin, Zhang, Yongda, Li, Ning, Lee, Heewon, Brazzillo, Jason, Nummy, Laurence J., Chung, J. C., Luvaga, Irungu K., Narayanan, Bikshandarkoil A., Wei, Xudong, Song, Jinhua J., Roschangar, Frank, Yee, Nathan K., Senanayake, Chris H.
A convergent, robust, and concise synthesis of a developmental CCR1 antagonist is described using continuous flow technology. In the first approach, following an expeditious SNAr sequence for cyclopropane introduction, a safe, continuous flow Curtius rearrangement was developed for the synthesis...
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Development of Continuous Filtration in a Novel Continuous Filtration Carousel Integrated with Continuous Crystallization
09 Jun 2023 | Contributor(s):: Liu, Yiqing C., Domokos, András, Coleman, Simon, Firth, Paul, Nagy, Zoltan K.
Pharmaceutical manufacturing has been largely carried out in batch mode, which has disadvantages such as batch-to-batch variations and difficult scale-up. As a result, the pharmaceutical industry is going through the paradigm shift to continuous manufacturing. Many unit operations have been...
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Continuous, one-step synthesis of pharmaceutical cocrystals via hot melt extrusion from neat to matrix-assisted processing - State of the art
09 Jun 2023 | Contributor(s):: Gajda, Maciej, Nartowski, Karol P., Pluta, Janusz, Karolewicz, Bożena
Use of hot melt extrusion (HME) as continuous manufacturing process in the cocrystal synthesis is of increasing interest from both industrial and academic perspective and it is seen as a newly developing branch of mechanochemistry with possible broad application in single step synthesis and...
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Continuous manufacturing – the Green Chemistry promise?
09 Jun 2023 | Contributor(s):: Klavs F. Jensen
Continuous manufacturing and Green Chemistry, are two promising approaches to synthesis with underutilized potential that are gaining traction by the wider pharmaceutical community. We review Green Chemistry advances resulting when transitioning to continuous manufacturing with focus on Green...
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Automated and continuous synthesis of drug substances
09 Jun 2023 | Contributor(s):: Sacher, Stephan, Castillo, Ismael, Rehrla, Jakob, Sagmeistera, Peter, Lebl, René, Kruisza, Julia, Celikovic, Selma, Sipek, Martin, Williams, Jason D, Kirschneck, Dirk, Kappea, C. Oliver, Horn, Martin
A continuous synthesis line was developed integrating different common reaction stepsnamely nitration, substitution and hydrogenation. Mesalazine as model drug substancewas produced from 2-chlorobenzoic acid in continuous flow mode. A multi-instrument PATstrategy was implemented to equip the full...
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Breaking Through Barriers to Continuous Manufacturing
09 Jun 2023 | Contributor(s):: Markarian, Jennifer
Pharmaceutical manufacturing is inching towards implementing more efficient and sustainable processes, including continuous manufacturing (CM) of solid-dosage drugs. Advantages of CM include the potential for faster development, easier technical transfer, and more efficient and flexible...