Authors
- Brenden Derstine ,
- John W. Tomlin ,
- Cheryl Peck ,
- Jule-Phillip Dietz ,
- Brenden Herrera ,
- Flavio S. P. Cardoso ,
- Dinesh J. Paymode ,
- Andrew C. Yue ,
- Anthony J. Arduengo III ,
- Till Opatz ,
- David R. Snead ,
- Rodger W. Stringham ,
- D. Tyler McQuade
Virginia Commonwealth University ,
- B. Frank Gupton
Abstract
Abstract: Herein, we report further improvements to the synthesis of tenofovir 1, the precursor to tenofovir disoproxil fumarate and tenofovir alafenamide fumarate. 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 more 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 eliminating the need for 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.
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