1070377-34-2

Usage

Uses

Used in Pharmaceutical Industry:
4-[6-Chloro-2-(4-cyano-phenylamino)-pyrimidin-4-yloxy]-3,5-dimethyl-benzonitrile is used as a by-product in the synthesis of Etravirine-d8, a labeled HIV reverse transcriptase inhibitor, for the treatment of HIV infection. Its presence in the synthesis process may provide insights into the development of new compounds or methods for the production of HIV treatments.

Upstream product

• 1225383-63-0 4-[(2,6-dichloro)-4-pyrimidinyloxy]-3,5-dimethylbenzonitrile 
• 873-74-5 4-Aminobenzonitrile 
• 4198-90-7 3,5-dimethyl-4-hydroxybenzonitrile 
• 623-03-0 4-Cyanochlorobenzene 
• 623-00-7 4-bromobenzenecarbonitrile 
• 374067-80-8 4-((4,6-dihydroxypyrimidine-2-yl)amino)benzonitrile 
• 5637-42-3 1-(4-cyanophenyl)guanidine 
• 329187-59-9 4-(4,6-dichloropyrimidine-2-yl-amino)benzonitrile 
• 3764-01-0 2,4,6-trichloropyrimidine 

Relevant academic research and scientific papers

Design, synthesis and evaluation of novel HIV-1 NNRTIs with dual structural conformations targeting the entrance channel of the NNRTI binding pocket

On the basis of structure-based bioisosteric replacement and molecular hybridization strategy, a series of novel dual structural-conformation inhibitors targeting the "entrance channel" of HIV-1 NNRTIs binding pocket (NNIBP) were designed and synthesized.

In situ click chemistry-based rapid discovery of novel HIV-1 NNRTIs by exploiting the hydrophobic channel and tolerant regions of NNIBP

HIV-1 RT has been considered as one of the most important targets for the development of anti-HIV-1 drugs for their well-solved three-dimensional structure and well-known mechanism of action. In this study, with HIV-1 RT as target, we used miniaturized pa

Substituted pyrimidine derivatives, and preparation method and application thereof

The invention discloses substituted pyrimidine compounds as shown in general formulas I-VI which are described in the specification, preparation methods of the substituted pyrimidine compounds, and application of compositions containing one or more of the

A etravirine preparation method

The invention discloses a preparation method for etravirine. The method comprises the following steps: performing nucleophilic substitution on a pyrimidine ring to generate an intermediate IV under the action of an alkali by taking a compound II and a compound III as initial raw materials; performing the nucleophilic substitution on the intermediate IV and aminobenzonitrile under an alkaline condition to generate a key intermediate V; performing ammoniation on the key intermediate V in a microwave reactor to generate an intermediate VI; performing bromination on the intermediate VI to generate a target product, namely the etravirine I. The preparation method disclosed by the invention is high in reaction selectivity and easy to operate; compared with the original synthetic method, the reaction time is greatly shortened; the energy consumption is reduced; the reaction yield is improved; the overall yield reaches 38.5 percent; the preparation method is suitable for industrial large-scale production.

PROCESS FOR ETRAVIRINE INTERMEDIATE AND POLYMORPHS OF ETRAVIRINE

4-[[6-chloro-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethyl-benzonitrile is a key intermediate for the preparation of etravirine. The present invention provides a process for preparation of 4-[[6-chloro-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethylbenzonitrile. The present invention also provides a novel process for the preparation of etravirine crystalline form I. The present invention further provides novel crystalline forms of etravirine, processes for their preparation and pharmaceutical compositions comprising them.

Novel piperidinylamino-diarylpyrimidine derivatives with dual structural conformations as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

A series of novel piperidinylamino-diarylpyrimidine (pDAPY) derivatives with dual structural conformations was designed through a molecular hybridization strategy and expected to bind into the non-nucleoside inhibitor binding pocket (NNIBP) of HIV-1 RT in

A PROCESS FOR ETRA VIRINE INTERMEDIATE AND POLYMORPHS OF ETRAVIRINE

4-[[6-chloro-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethyl- benzonitrile is a key intermediate for the preparation of etravirine. The present invention provides a process for preparation of 4-[[6-chloro-2-[(4-cyanophenyl)amino]-4- pyrimidinyl]oxy]-3,5-dimethylbenzonitrile. The present invention also provides a novel process for the preparation of etravirine crystalline form I. The present invention further provides novel crystalline forms of etravirine, processes for their preparation and pharmaceutical compositions comprising them.

PROCESS FOR SYNTHESIS OF DIARYLPYRIMIDINE NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR

A method for synthesis of diarylpyrimidine non-nucleoside reverse transcriptase inhibitor such as etravirine is provided Typically, etravirine is synthesized by the steps of a Condensing 2,4,6-trichlorpyrimidine with 3,5-dimethyl-4-hydroxybenzonitrile to obtain compound (V), b Condensing compound (V) with 4-aminobenzonitrile to obtain compound (VI), c Ammonolysis of compound (VI) to get compound (IV), d Halogenation of compound (IV) to get etravirine.

PROCESS FOR THE PREPARATION AND PURIFICATION OF ETRAVIRINE AND INTERMEDIATES THEREOF

In one embodiment the present invention encompasses 4-(2,6-dichloropyrimidin-4-yloxy)-3,5-dimethylbenzonitrile ("ΕTHER"), 4-(4,6-dichloropyrimidm-2-yloxy)-3,5-dimethyl-benzonitrile ("ETHER C-2 isomer"), mixtures and salts thereof of. The present invention encompasses the use of ETHER and salts thereof to prepare Etravirine and Etravirine intermediates, and salts thereof. In another embodiment the present invention encompasses the use of ETHER and salts thereof to prepare debrometravirine ("DEBETV") and salts thereof. In yet another embodiment the present invention encompasses the use of ETHER and salts thereof to prepare 4-(6-chloro-2-(4-cyanophenylamino)pyrimidin-4-yloxy)-3,5-dimethyl-benzonitrile("ARCPBN") and salts thereof. The compound, 4-(2,6-dichloropyrimidin-4-yloxy)-3,5-dimethylbenzonitrile "ETHER" of formula (A) wherein n is either 0 or 1 and HA is an acid.

PROCESS FOR SYNTHESIS OF DIARYLPYRIMIDINE NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR

A method for synthesis of diarylpyrimidine non-nucleoside reverse transcriptase inhibitor such as etravirine is provided. Typically, etravirine is synthesized by the steps of : a. Condensing 2,4,6-trichlorpyrimidine with 3,5-dimethyl-4-hydroxybenzonitrile to obtain compound (V); b. Condensing compound (V) with 4-aminobenzonitrile to obtain compound (VI); c. Ammonolysis of compound (VI) to get compound (IV); d. Halogenation of compound (IV) to get etravirine.