RILPIVIRINE HCL Property

storage temp. 

Store at -20°C

solubility 

DMSO:50.0(Max Conc. mg/mL);136.46(Max Conc. mM)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H319Causes serious eye irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P330Rinse mouth.

P501Dispose of contents/container to..…

RILPIVIRINE HCL Chemical Properties,Usage,Production

Uses

Rilpivirine Hydrochloride was shown to be able to treat and or prevent immunodeficiency virus-1. It also has uses for anti-viral therapy

Definition

ChEBI: A hydrochloride obtained by reaction of rilpivirine with one equivalent of hydrochloric acid. Used for treatment of HIV.

Clinical Use

Rilpivirine hydrochloride (Edurant), a non-nucleoside reverse transcriptase inhibitor (NNRTI), received its approval both from the U.S. FDA and E.U. EMA in 2011 for the treatment of HIV-1 infection in treatment-na?ve adult patients. It was discovered and developed by Janssen Pharmaceuticals and its subsidiary Tibotec Pharmaceuticals. As a second generation NNRTI, rilpivirine hydrochloride displayed higher potency and longer half-life with a 25 mg once a day dose, compared to existing NNRTIs, such as the 200 mg BID of efavirenze (Sustiva). In late 2011, the fixed-dose combination products of rilpivirine hydrochloride with two nucleoside reverse transcriptase inhibitor (RTIs) emtricitabine and tenofovir disoproxil fumarate, co-developed by Gilead Science and Tibotec, were also approved both by the FDA and EMA under brand names Complera® and Eviplera®, respectively.

Synthesis

Similar to efavirenze, rilpivirine hydrochloride is a diarylpyrimidine (DAPY) compound, and the large-scale process synthesis begins with commercially available 2-methylthio-4-pyrimidinone (193) shown in the scheme.

Thioether 193 was condensed with neat 4-cyanoaniline (194) at elevated temperature to afford diarylamine 195 in 77% yield. Subsequent treatment of pyrimidone 195 with refluxing POCl3 provided the corresponding chloride 196 in 77% yield.160,161 In the presence of K2CO3, chloride 196 was treated with the (E)-cinnamonitrile aniline 200 to give rilpivirine hydrochloride (XIX) in good yield.158 Aniline 200 was prepared via a Heck reaction of commercially available 4-iodo-2,6-dimethyl-benzeneamine (197) and acrylonitrile (198) affording compound 199 as a 4:1 mixture of E/Z isomers. The distribution of E/Z olefins was increased to 98:2 by salt formation and recrystallization to ultimately provide pure (E)-200 in 64% yield for two steps.