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7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir
Author(s) -
Ziegler Robert E.,
Desai Bimbisar K.,
Jee JoAnn,
Gupton B. Frank,
Roper Thomas D.,
Jamison Timothy F.
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201802256
Subject(s) - dolutegravir , integrase , flow chemistry , human immunodeficiency virus (hiv) , active ingredient , combinatorial chemistry , chemistry , virology , organic chemistry , pharmacology , medicine , antiretroviral therapy , catalysis , viral load
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.
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