Authors
Brenden P Derstine, John W Tomlin, Cheryl L Peck, Jule-Phillip Dietz, Brenden T Herrera, Flavio SP Cardoso, Dinesh J Paymode, Andrew C Yue, Anthony J Arduengo III, Till Opatz, David R Snead, Rodger W Stringham, D Tyler McQuade, B Frank Gupton
Publication date
2020/5/29
Journal
Organic Process Research & Development
Volume
24
Issue
8
Pages
1420-1427
Publisher
American Chemical Society
Description
Herein, we report further improvements to the synthesis of tenofovir 1, the precursor to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF). Starting from acyclic precursor diaminomalononitrile 12, a four-step protocol to tenofovir 1 will allow for vertical integration for more manufacturers. The key transformation is a convergent one-step procedure from 6 as compared to the current commercial process, with an improved yield from 59% (two steps) to 70%. Further improvements include eliminating the need for problematic magnesium tert-butoxide (MTB) and significant solvent reduction by avoiding an intermediate workup. With the costs of HIV/AIDS treatments remaining a barrier for those most in need, lowering the raw material/processing costs and increasing the security of supply can increase patient access.
Total citations
2020202120222023202444643
Scholar articles
BP Derstine, JW Tomlin, CL Peck, JP Dietz, BT Herrera… - Organic Process Research & Development, 2020