950596-58-4

Usage

Uses

Used in Pharmaceutical Industry:
2-Amino-4,5-bis(2-methoxyethoxy)benzonitrile is used as an impurity in Erlotinib (E625008), an EGFR-targeted drug for the treatment of non-small cell lung cancer. As an EGFR small tyrosine kinase inhibitor, Erlotinib has a significant effect on tumor growth inhibition and animal survival. The presence of this impurity may affect the drug's efficacy and safety, and therefore, it is important to monitor and control its levels during the manufacturing process.

Upstream product

• 236750-65-5 4,5-bis(2-methoxyethoxy)-2-nitrobenzonitrile 
• 80407-68-7 3,4-bis(2-methoxyethoxy)-benzonitrile 
• 1418289-91-4 3,4-bis(2-methoxyethoxy)-benzamide 
• 819813-71-3 3,4-bis(2-methoxyethoxy)-benzoic acid 
• 99-50-3 3,4-Dihydroxybenzoic acid 

Downstream Products

• 183321-74-6 erlotinib 
• 950596-59-5 N′-[2-cyano-4,5-{bis(2-methoxyethoxy)phenyl}]-N,N-dimethylformamidine 
• 183319-69-9 erlotinib hydrochloride 
• 766497-25-0 N-(3-trimethylsilyl-ethynyl)-6,7-bis(2-methoxyethoxy)-4-quinolyl-amine 
• 899830-10-5 N-(3-ethynyl phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine 
• 1246445-24-8 erlotinib trifluoroacetate 

Relevant academic research and scientific papers

METHOD AND CATALYST FOR PREPARING ANILINE COMPOUNDS AND USE THEREOF

The present invention provides a method for preparing aniline compounds, and also provides a kind of catalyst and use thereof. This method for synthesizing an aniline compound in the invention includes following steps: use molybdenum oxide and activated carbon as catalyst, hydrazine hydrate as reducing agent, then reduce aromatic nitro compounds to aniline compounds. This method is green and high efficiency, and easy to be applied in industry.

Method for synthesizing aniline compound, catalyst and application thereof

The invention provides a method for synthesizing an aniline compound, and further provides a catalyst and an application thereof. The method for synthesizing the aniline compound includes the following steps: taking molybdenum-based oxide and activated carbon as catalysts; taking hydrazine hydrate as a reducing agent; and reducing an aromatic nitro compound to the aniline compound. The method forsynthesizing the aniline compound has the characteristics of green and high efficiency, easy industrial application and the like.

Method for synthesizing erlotinib intermediate with microchannel reactor

The invention discloses a method for synthesizing an erlotinib intermediate with a microchannel reactor, belongs to the field of synthesis of anti-tumor drugs in organic synthesis and solves the problems of low yield, poor purity, high energy consumption,

Novel 4-arylaminoquinazoline derivatives with (E)-propen-1-yl moiety as potent EGFR inhibitors with enhanced antiproliferative activities against tumor cells

A series of novel 4-anilinoquinazoline derivatives with (E)-propen-1-yl moiety were designed, synthesized and evaluated for biological activities in vitro. Most compounds exhibited highly antiproliferative activities against all tested tumor cell lines in

An improved convergent approach for synthesis of erlotinib, a tyrosine kinase inhibitor, via a ring closure reaction of phenyl benzamidine intermediate

An improved convergent and economical method has been developed for the synthesis of erlotinib, a 4-anilinoquinazoline and an EGFR-tyrosine kinase inhibitor for treatment of non-small-cell lung cancer. The final two steps for the formation of this 4-anilinoquinazoline from suitable 2-aminobenzonitrile intermediate and 3-ethynylaniline were modified and were performed in a simple one-pot reaction. The ring-closing mechanism for the formation of erlotinib from the suitable formamidine intermediate and 3-ethynylaniline was investigated and determined to proceed via the formation of phenyl benzamidine intermediate rather than involving Dimroth rearrangement reported earlier. The new benzamidine intermediate was isolated for the first time and characterized. Copyright

Convergent approach for commercial synthesis of gefitinib and erlotinib

An efficient, economical and large-scale convergent synthesis of epidermal growth factor receptor- tyrosine kinase inhibitors gefitinib (1, Iressa) and erlotinib (2, Tarceva) approved by U.S. FDA for the treatment of non-small-cell lung cancer is described. The formation of 4-anilinoquinazolines are achieved in a simple one-pot reaction of suitable forniamidine intermediates and substituted anilines involving Dimroth rearrangement, thereby avoiding the need to make quinazolin-4(3H)-one intermediates, which require a large experimental inputs. Using this process, we have produced drug candidates 1 with overall yield of 66% from 4-methoxy-5-[3-(4-morpholinyl) propoxy]-2-nitrobenzonitrile (3) and 2 with 63% from 4-bis(2-methoxyethoxy)-2-nitrobenzonitrile (6) on a multigram scale.

A PROCESS FOR SYNTHESIS OF [6,7-BIS-(2-METHOXYETHOXY)-QUINAZOLIN-4- YL]-(3-ETHYNYLPHENYL)AMINE HYDROCHLORIDE

A process for synthesizing [6,7-bis(2-methoxyethoxy)quinazolin-4-yl]-(3-ethynylphenyl)amine hydrochloride (Erlitinib Hydrochloride) having the formula (I) comprising reacting 3,4-dihydroxy benzaldehyde with bromo derivative of ethyl methyl ether to obtain 3,4-bis(2-methoxyethoxy)benzaldehyde having formula (III). This is converted to give 3,4- bis (2-methoxyethoxy)-benzonitrile. On further nitration we obtain 4,5- bis (2-methoxyethoxy)-2-nitrobenzonitrile which on nitro reduction we get 2-amino-4,5-bis(2-methoxyethoxy)benzonitrile and reacting this with N'-(3-ethynylphenyl)-N,N-dimethyl formamidine gives erlotinib free base. On further treatment of this free base with methanolic/ethanolic hydrochloric acid gives us erlotinib hydrochloride.

A PROCESS FOR SYNTHESIS OF [6,7-BIS-(2-METHOXYETHOXY)-QUINAZOLIN-4-YL]-(3-ETHYNYLPHENYL)AMINE HYDROCHLORIDE

The present invention provides a process for synthesizing [6,7-bis(2-methoxyethoxy)quinazolin-4-yl]-(3-ethynylphenyl)amine hydrochloride (Erlitinib Hydrochloride) having the formula (I) comprising reacting 3,4-dihydroxy benzaldehyde with bromo derivative of ethyl methyl ether to obtain 3,4-bis(2-methoxyethoxy)benzaldehyde having formula (III). This is converted to give 3,4- bis (2-methoxyethoxy)-benzonitrile which on furthur nitration we obtain 4,5- bis (2-methoxyethoxy)-2-nitrobenzonitrile which on nitro reduction we get 2-amino-4,5-bis(2-methoxyethoxy)benzonitrile. Formylation of this compound yields N'-[2-cyano-4,5-bis(2methoxyethoxy)phenyl]-N,N-dimethylformamidine. Coupling of this formamidine with 3-ethynyl aniline gives erlotinib free base. On furthur treatment of this free base with methanolic/ethanolic hydrochloric acid gives us erlotinib hydrochloride.