6533b7dbfe1ef96bd1270160

RESEARCH PRODUCT

An Efficient Synthesis of Tenofovir (PMPA): A Key Intermediate Leading to Tenofovir-Based HIV Medicines

Jule-phillip DietzBrenden T. HerreraTill OpatzBrenden P. DerstineAnthony J. ArduengoCheryl L. PeckB. Frank GuptonD. Tyler McquadeJohn W. TomlinFlavio S. P. CardosoAndrew C. YueRodger W. StringhamDavid R. SneadDinesh J. Paymode

subject

Tenofovir010405 organic chemistrybusiness.industryOrganic ChemistryHuman immunodeficiency virus (HIV)Continuous manufacturingPharmacology010402 general chemistrymedicine.disease_causemedicine.disease01 natural sciencesTenofovir alafenamide0104 chemical sciencesAcquired immunodeficiency syndrome (AIDS)DiaminomaleonitrilemedicinePhysical and Theoretical ChemistrySecurity of supplybusinessmedicine.drug

description

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.

yearjournalcountryeditionlanguage
2020-02-26
https://doi.org/10.26434/chemrxiv.11900262