The development of an effective synthetic route of rilpivirine

Abstract

Background Rilpivirine (RPV) was approved by the U.S. FDA (Food and Drug Administration) in 2011 to treat individuals infected with human immunodeficiency virus 1 (HIV-1). Significantly, rilpivirine is three fold more potent than etravirine. Once-daily, it is used with a low oral dose (25 mg/tablet), decreasing the drug administration and bringing a better choice to the patients. However, there are many shortcomings in the existing synthesis route of RPV, such as the high cost, prolonged reaction time and low yield (18.5%). Results This article describes our efforts to develop an efficient and practical microwave-promoted method to synthesize rilpivirine using less toxic organic reagents and low boiling solvents. The last step's reaction time decreased from 69 h to 90 min through this optimized synthetic procedure, and the overall yield improved from 18.5 to 21%. In addition, the yield of intermediate 3 increased from 52 to 62% compared to the original patent. Conclusion Overall, through a series of process optimization, we have developed a practical synthesis method of rilpivirine, which is easy to scale with higher yield and shorter reaction time.

Stereoselective synthesis of vinyl nitriles through a Ramberg–Bäcklund approach

“…33 Both routes require the use of catalysts based on transition metals (e.g., Pd(OAc) 2 , P(oTol) 3 , and Pd/C), which are not ideal for industrial setups. 34 Our approach to access arylacrylonitriles through the RBR seemed ideal for the development of a transition metal-free formal synthesis of rilpivirine through the preparation of 3 (Scheme 2b). Masked benzylmercaptane 6 was obtained from aminoalcohol 5 by a thio-Mitsunobu reaction, followed by tandem acetyl cleavage/S-alkylation using chloroacetonitrile under basic media, and oxidation with Oxone® to deliver sulfone precursor 7.…”

Non-nucleoside structured compounds with antiviral activity—past 10 years (2010–2020)

“…Rilpivirine hydrochloride (component of Complera®) was approved by FDA in 2011. Synthesis has been developed but is constantly being refined [ 109 ].…”