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Use of a “Catalytic” Cosolvent, N,N-Dimethyl Octanamide, Allows the Flow Synthesis of Imatinib with no Solvent Switch
Contributor(s):: Yang, Jeffrey C., Niu, Dawen, Karsten, Bram P., Lima, Fabio, Buchwald, Stephen L.
A general, efficient method for C−N cross-coupling has been developed using N,N-dimethyloctanamide as a catalytic cosolvent for biphasic continuous-flow applications. The described method was used to generate a variety of biarylamines and was integrated into a two-step sequence which converted...
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Integrated multi-step continuous flow synthesis of daclatasvir without intermediate purification and solvent exchange
Contributor(s):: Rana, Abhilash, Mahajan, Bhushan, Ghosh, Subhash, Srihari, Pabbaraja, Singh, Ajay K.
The rapid transmission of viral diseases can cause massive economic damage and loss of life. The manufacture of most anti-viral drugs is normally carried out using batch synthesis which typically requires long production times (3–15 days) and significant manpower and infrastructure. The...
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Preparation of fluoxetine by multiple flow processing steps
Contributor(s):: Ahmed-Omer, Batoul, Sanderson, Adam J.
Microflow technology is established as a modern and fashionable tool in synthetic organic chemistry, bringing great improvement and potential, on account of a series of advantages over flask methods. The study presented here focuses on the application of flow chemistry process in performing an...
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Process Intensification and Integration Studies for the Generation of a Key Aminoimidazole Intermediate in the Synthesis of Lanabecestat
Contributor(s):: Znidar, D, Cantillo, DInglesby, P, Boyd, A, Kappe, CO
An improved synthetic procedure for the multistep synthesis of aminoimidazole 6, a key intermediate in the preparation of lanabecestat (AZD3293/LY3314814), is described. Under intensified conditions (high temperature and elevated pressure), the overall processing time and required amounts of...
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Advanced Real-Time Process Analytics for Multistep Synthesis in Continuous Flow
Contributor(s):: Sagmeister, Peter, Lebl, René, Castillo, Ismael, Rehrl, Jakob, Kruisz, Julia, Sipek, Martin, Horn, Martin, Sacher, Stephan, Cantillo, David, Williams, Jason D, Kappe, Oliver
In multistep continuous flow chemistry, studying complex reaction mixtures in real time is a significant challenge, but provides an opportunity to enhance reaction understanding and control. We report the integration of four complementary process analytical technology tools (NMR, UV/Vis, IR and...
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7-Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir
| Contributor(s):: Ziegler, RE, Desai, BKJee, JA, Gupton, BF, Roper, TD, Jamison, TF
Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5h in sequential...