7-step flow synthesis of the HIV integrase inhibitor Dolutegravir
Author(s)Ziegler, Robert E.; Desai, Bimbisar K.; Jee, Jo-Ann; Gupton, B. Frank; Roper, Thomas D.; Jamison, Timothy F; ... Show more Show less
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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 4.5 h in sequential flow operations from commercially available materials. Key features of the synthesis include rapid manufacturing time for pyridone formation, one-step direct amidation of a functionalized pyridone, and telescoping of multiple steps to avoid isolation of intermediates and enable for greater throughput.
DepartmentMassachusetts Institute of Technology. Department of Chemistry
Angewandte Chemie International Edition
Ziegler, Robert E., et al., "7-step flow synthesis of the HIV integrase inhibitor Dolutegravir." Angewandte Chemie International Edition 57, 24 (June 2018): p. 7181-85 doi 10.1002/ANIE.201802256 ©2018 Author(s)
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