Rilpivirine

Base Information

• Chemical Name: Rilpivirine
• CAS No.: 500287-72-9
• Molecular Formula: C22H18N6
• Molecular Weight: 366.425
• Hs Code.: 2933599090
• European Community (EC) Number: 695-719-5
• UNII: FI96A8X663
• DSSTox Substance ID: DTXSID10198189
• Nikkaji Number: J2.576.528A,J2.980.206H
• Wikipedia: Rilpivirine
• Wikidata: Q421547
• NCI Thesaurus Code: C76929
• RXCUI: 1102270
• Pharos Ligand ID: 3ZHBK2D9PUKP
• Metabolomics Workbench ID: 65119
• ChEMBL ID: CHEMBL175691
• Mol file: 500287-72-9.mol

Synonyms:278, TMC;HCl, Rilpivirine;Hydrochloride, Rilpivirine;R278474;Rilpivirine;Rilpivirine HCl;Rilpivirine Hydrochloride;TMC 278;TMC-278;TMC278

Chemical Property of Rilpivirine

Chemical Property:

• Vapor Pressure: 5.56E-16mmHg at 25°C
• Melting Point: 245 °C
• Refractive Index: 1.665
• Boiling Point: 634.1 °C at 760 mmHg
• PKA: 4.56±0.10(Predicted)
• Flash Point: 337.3 °C
• PSA: 97.42000
• Density: 1.27 g/cm³
• LogP: 5.13506
• Storage Temp.: Refrigerator
• Solubility.: Acetone (Slightly), Chloroform (Slightly), DMSO (Slightly), Water (Very Slightly
• XLogP3: 4.5
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 366.15929460
• Heavy Atom Count: 28
• Complexity: 607

Purity/Quality:

≥95% ^*data from raw suppliers

Rilpivirine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiviral Agents
• Canonical SMILES: CC1=CC(=CC(=C1NC2=NC(=NC=C2)NC3=CC=C(C=C3)C#N)C)C=CC#N
• Isomeric SMILES: CC1=CC(=CC(=C1NC2=NC(=NC=C2)NC3=CC=C(C=C3)C#N)C)/C=C/C#N
• Recent ClinicalTrials: A Study to Evaluate Efficacy and Safety of Cabotegravir (CAB) Long Acting (LA) Plus (+) Rilpivirine (RPV) LA Versus BIKTARVY? (BIK) in Participants With Human Immunodeficiency Virus (HIV)-1 Who Are Virologically Suppressed
• Recent EU Clinical Trials: HIV-1 RNA suppression and drug concentrations in semen, cervicovaginal fluid and rectum in HIV-1 infected individuals receiving intramuscular long-acting cabotegravir plus rilpivirine (“CAR-GR Study)
• Description: In May 2011, the U.S. FDA approved rilpivirine in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV) 1 infection in treatment-naive adult patients. Rilpivirine is a member of the nonnucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV agents. It is highly potent against a range of wild-type HIV strains (EC50=0.07–1.0 nM),～10–20 timesmore potent than the NNRTI efavirenz (Sustiva), and active against HIV strains resistant to other NNRTIs. The discovery of rilpivirine was guided by molecular modeling and X-ray crystallography of HIV-1 RT complexed with inhibitors. The synthesis of rilpivirine is accomplished by an efficient 6-step route in which the key step is coupling of 4-((4-chloropyrimidin-2-yl)amino)benzonitrile with (E)-3-(4-amino-3,5-dimethylphenyl)acrylonitrile.
• Uses: A novel non-nucleoside reverse transcriptase inhibitor. Rilpivirine seems to be well tolerated with less CNS disturbance than Efavirenz, and has non-teratogenic potential. An anti-HIV agent. A novel non-nucleoside reverse transcriptase inhibitor. Rilpivirine seems to be well tolerated with less CNS disturbance than Efavirenz, and has non-teratogenic potential.
• Clinical Use: Non-nucleoside reverse transcriptase inhibitor: Treatment of progressive or advanced HIV infection in combination with at least two other antivirals
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: avoid with clarithromycin and erythromycin - concentration possibly increased; concentration decreased by rifampicin and rifabutin - avoid with rifampicin, increase dose of rilpivirine to 50 mg daily. Antidepressants: concentration possibly reduced by St John’s wort - avoid. Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin, oxcarbazepine, phenobarbital, primidone and phenytoin - avoid. Corticosteroids: avoid with dexamethasone (except as a single dose). Orlistat: absorption possibly reduced by orlistat. Ulcer-healing drugs: concentration possibly reduced by esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole - avoid; avoid histamine H2 -antagonists for 12 hours before and 4 hours after rilpiverine.

Technology Process of Rilpivirine

There total 36 articles about Rilpivirine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 97.8%

4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile → rilpivirine (500287-72-9)

Guidance literature:

With succinic acid; In acetonitrile; at 60 ℃; Reagent/catalyst; Solvent; Temperature; Large scale; Industrial scale;

Reference yield: 93.9%

(E)- 3-{4-[2-(4-(cyanophenylamino)-1-oxo-pyrimidin-4-yl)amino]-3,5-dimethylphenyl}acrylamide (500288-66-4) → rilpivirine (500287-72-9)

Guidance literature:

With trichlorophosphate; at 20 ℃; Reflux;

Reference yield: 89.6%

(2E)-3-(4-amino-3,5-dimethylphenyl)prop-2-enenitrile hydrochloride (661489-23-2) + 4-[(4-chloro-2-pyrimidinyl)amino]benzonitrile (244768-32-9) → rilpivirine (500287-72-9)

Guidance literature:

(2E)-3-(4-amino-3,5-dimethylphenyl)prop-2-enenitrile hydrochloride; 4-[(4-chloro-2-pyrimidinyl)amino]benzonitrile; In acetonitrile; at 50 ℃; for 24h; Heating / reflux;

With potassium carbonate; In water; acetonitrile; at 40 - 50 ℃; for 1.25 - 1.33h;

In ethanol; for 2h; Heating / reflux;

upstream raw materials:

(cyanomethyl)triphenylphosphonium chloride

4-[4-(4-formyl-2,6-dimethylphenylamino)pyrimidin-2-ylamino]benzonitrile

acrylonitrile

4-((4-((4-bromo-2,6-dimethylphenyl)amino)pyrimidin-2-yl)amino)benzonitrile

Downstream raw materials:

C₂₂H₁₇BrN₆

Refernces

• 1、 -. "A METHOD OF PRODUCING HIGHLY PURE RILPIVIRINE AND ITS SALTS". Page/Page column 4; 5. . Retrieved 2016/08/17.
• 2、 -. "Pharmaceutical compositions comprising a basic drug compound, a surfactant, and a physiologically tolerable water soluble acid". Page/Page column 73-74. . Retrieved 2015/12/04.