7-step flow synthesis of the HIV integrase inhibitor Dolutegravir
Name
Ziegler_et_al-2018-Angewandte_Chemie_International_Edition.pdf
Description
Published version
Size
692.49 KB
Format
Adobe PDF
Checksum (MD5)
36133c2006b11e261647f7c07d497b3a
Author(s)
Ziegler, Robert E.
Desai, Bimbisar K.
Jee, Jo-Ann
Gupton, B. Frank
Roper, Thomas D.
Jamison, Timothy F
Date Issued
June 2018
Journal
Angewandte Chemie International Edition
Publisher
Wiley
Citation
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)
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/ANIE.201802256
