244767-67-7

Basic information

• Product Name: DAPIVIRINE,4-[[4-(2,4,6-TRIMETHYLPHENYL)AMINO]PYRIMIDIN-2-YL]AMINO]BENZONITRILE
• Synonyms: DAPIVIRINE,4-[[4-(2,4,6-TRIMETHYLPHENYL)AMINO]PYRIMIDIN-2-YL]AMINO]BENZONITRILE;Dapivirine;4-[[4-[(2,4,6-TriMethylphenyl)aMino]-2-pyriMidinyl]aMino]benzonitrile;R 147681;TMC 120R147681;Benzonitrile, 4-[[4-[(2,4,6-triMethylphenyl)aMino]-2-pyriMidinyl]aMino]-;Dapivirine,TMC-120;Dapivirine TMC120, AIDS-105293
• CAS NO: 244767-67-7
• Molecular Formula: C₂₀H₁₉N₅
• Molecular Weight: 329.405
• Product Categories: pharmacetical;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Non-nucleoside Reverse Transcriptase;Pharmaceuticals;API;Inhibitors
• Mol File: 244767-67-7.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 557.9 °C at 760 mmHg
• Flash Point: 291.2 °C
• Appearance: /
• Density: 1.23 g/cm³
• Vapor Pressure: 1.76E-12mmHg at 25°C
• Refractive Index: 1.648
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 4.74±0.10(Predicted)
• CAS DataBase Reference: DAPIVIRINE,4-[[4-(2,4,6-TRIMETHYLPHENYL)AMINO]PYRIMIDIN-2-YL]AMINO]BENZONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: DAPIVIRINE,4-[[4-(2,4,6-TRIMETHYLPHENYL)AMINO]PYRIMIDIN-2-YL]AMINO]BENZONITRILE(244767-67-7)
• EPA Substance Registry System: DAPIVIRINE,4-[[4-(2,4,6-TRIMETHYLPHENYL)AMINO]PYRIMIDIN-2-YL]AMINO]BENZONITRILE(244767-67-7)

Safety Data

• Hazardous Substances Data: 244767-67-7(Hazardous Substances Data)

Usage

Chemical Properties

Light Beige Solid

Uses

Different sources of media describe the Uses of 244767-67-7 differently. You can refer to the following data:
1. Non-nucleoside Reverse Transcriptase inhibitor. An antiviral agent.
2. Non-nucleoside Reverse Transcriptase inhibitor. An antiviral agent

InChI:InChI=1/C20H19N5/c1-13-10-14(2)19(15(3)11-13)24-18-8-9-22-20(25-18)23-17-6-4-16(12-21)5-7-17/h4-11H,1-3H3,(H2,22,23,24,25)

Synthetic route

potassium cyanide + C19H19BrN4 → dapivirine (244767-67-7)

Conditions	Yield
Stage #1: potassium cyanide With acetic acid In ethylene glycol Sealed tube; Stage #2: C19H19BrN4 With P(t-Bu)3 Palladacycle Gen. 3; potassium acetate In 1,4-dioxane; water at 60℃; for 16h; Sealed tube;	96%

2-chloro-N-mesitylpyrimidin-4-amine + 4-Aminobenzonitrile (873-74-5) → dapivirine (244767-67-7)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; ethanol Reflux;	42%

2,4,6-trimethylaniline (88-05-1) + 4-[(4-chloro-2-pyrimidinyl)amino]benzonitrile hydrochloride → dapivirine (244767-67-7)

Conditions	Yield
In 1,4-dioxane

4-Aminobenzonitrile (873-74-5) → dapivirine (244767-67-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 20 °C 2: N-ethyl-N,N-diisopropylamine / tetrahydrofuran 3: palladium on activated charcoal; hydrogen View Scheme

4-(4-chloro-6-(mesitylamino)pyrimidin-2-ylamino)benzonitrile (1452007-28-1) → dapivirine (244767-67-7)

Conditions	Yield
With palladium on activated charcoal; hydrogen

4-((4,6-dichloropyrimidin-2-yl)amino)benzonitrile (329187-59-9) → dapivirine (244767-67-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran 2: palladium on activated charcoal; hydrogen View Scheme

2,4,6-trimethylaniline (88-05-1) → dapivirine (244767-67-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: isopropyl alcohol / Reflux 2: hydrogenchloride / tetrahydrofuran; ethanol / Reflux View Scheme

NaBO3.4H2O + dapivirine (244767-67-7) → 4-[[4-[(2,4,6-trimethylphenyl)amino]-2-pyrimidinyl]amino]benzamide

Conditions	Yield
In methanol; water	0.586 g (56%)

Upstream product

• 244768-44-3 2-chloro-N-mesitylpyrimidin-4-amine 
• 873-74-5 4-Aminobenzonitrile 
• 88-05-1 2,4,6-trimethylaniline 
• 329187-59-9 4-(4,6-dichloropyrimidine-2-yl-amino)benzonitrile 
• 1452007-28-1 4-(4-chloro-6-(mesitylamino)pyrimidin-2-ylamino)benzonitrile 

Relevant articles and documents

Ex situ generation of stoichiometric HCN and its application in the Pd-catalysed cyanation of aryl bromides: Evidence for a transmetallation step between two oxidative addition Pd-complexes

A protocol for the Pd-catalysed cyanation of aryl bromides using near stoichiometric and gaseous hydrogen cyanide is reported for the first time. A two-chamber reactor was adopted for the safe liberation of ex situ generated HCN in a closed environment, which proved highly efficient in the Ni-catalysed hydrocyanation as the test reaction. Subsequently, this setup was exploited for converting a range of aryl and heteroaryl bromides (28 examples) directly into the corresponding benzonitriles in high yields, without the need for cyanide salts. Cyanation was achieved employing the Pd(0) precatalyst, P(tBu)3-Pd-G3 and a weak base, potassium acetate, in a dioxane-water solvent mixture. The methodology was also suitable for the synthesis of 13C-labelled benzonitriles with ex situ generated 13C-hydrogen cyanide. Stoichiometric studies with the metal complexes were undertaken to delineate the mechanism for this catalytic transformation. Treatment of Pd(P(tBu)3)2 with H13CN in THF provided two Pd-hydride complexes, (P(tBu)3)2Pd(H)(13CN), and [(P(tBu)3)Pd(H)]2Pd(13CN)4, both of which were isolated and characterised by NMR spectroscopy and X-ray crystal structure analysis. When the same reaction was performed in a THF : water mixture in the presence of KOAc, only (P(tBu)3)2Pd(H)(13CN) was formed. Subjection of this cyano hydride metal complex with the oxidative addition complex (P(tBu)3)Pd(Ph)(Br) in a 1 : 1 ratio in THF led to a transmetallation step with the formation of (P(tBu)3)2Pd(H)(Br) and 13C-benzonitrile from a reductive elimination step. These experiments suggest the possibility of a catalytic cycle involving initially the formation of two Pd(ii)-species from the oxidative addition of LnPd(0) into HCN and an aryl bromide followed by a transmetallation step to LnPd(Ar)(CN) and LnPd(H)(Br), which both reductively eliminate, the latter in the presence of KOAc, to generate the benzonitrile and LnPd(0).

Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility

Non-nucleoside inhibitors of HIV-1 reverse transcriptase are reported that have ca. 100-fold greater solubility than the structurally related drugs etravirine and rilpivirine, while retaining high anti-viral activity. The solubility enhancements come from strategic placement of a morpholinylalkoxy substituent in the entrance channel of the NNRTI binding site. Compound 4d shows low-nanomolar activity similar to etravirine towards wild-type HIV-1 and key viral variants.

RATE-CONTROLLED PARTICLES

Rate-controlled particles, comprising compounds of the formula as a solid dispersion.