7-Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir
Category
Published on CMKC
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 4.5h 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.
Journal
Angewandte Chemie International Edition. Volume 57, 2018, 7181-7185
DOI
10.1002/anie.201802256, 10.1002/anie.201809594
Type of publication
Peer-reviewed journal
Affiliations
- Massachusetts Institute of Technology (MIT) (MIT)
- Virginia Commonwealth University
Article Classification
Research Article
Classification Areas
- API