35202-54-1

Basic information

• Product Name: 4,5-Dimethoxy-1-cyanobenzocyclobutane
• Synonyms: 3,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile;4,5-Dimethoxy-1-benzocyclobutenecarbonitrile;4,5-Dimethoxy-1-cyanobenzocyclobutane;3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-8-carbonitrile;Bicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile,3,4-diMethoxy-;4,5-DiMethxoy-1,2-dihydrocyclobutabenzene-1-carbonitrile;2-cyclobutyl-2-(3,4-diMethoxyphenyl)acetonitrile;1,2-Dihydro-4,5-diMethoxybenzocyclobutene-1-carbonitrile
• CAS NO: 35202-54-1
• Molecular Formula: C₁₁H₁₁NO₂
• Molecular Weight: 189.21
• EINECS: 1592732-453-0
• Mol File: 35202-54-1.mol

Chemical Properties

• Melting Point: 83-84 °C
• Boiling Point: 345.9 °C at 760 mmHg
• Flash Point: 140.5 °C
• Appearance: /
• Density: 1.18
• Vapor Pressure: 5.98E-05mmHg at 25°C
• Refractive Index: 1.557
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO, Methanol
• CAS DataBase Reference: 4,5-Dimethoxy-1-cyanobenzocyclobutane(CAS DataBase Reference)
• NIST Chemistry Reference: 4,5-Dimethoxy-1-cyanobenzocyclobutane(35202-54-1)
• EPA Substance Registry System: 4,5-Dimethoxy-1-cyanobenzocyclobutane(35202-54-1)

Safety Data

• Hazardous Substances Data: 35202-54-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4,5-Dimethoxy-1-cyanobenzocyclobutane is used as a key intermediate in the synthesis of selective bradycardic agents. These agents are designed to slow down the heart rate, which can be beneficial in treating conditions like tachycardia and certain arrhythmias. 4,5-Dimethoxy-1-cyanobenzocyclobutane's structural features allow for the development of targeted therapies with minimal side effects.
Additionally, 4,5-Dimethoxy-1-benzocyclobutenecarbonitrile, a related compound, is also used in the preparation of selective bradycardic agents. This highlights the versatility and importance of the benzocyclobutane framework in the development of cardiovascular medications.

InChI:InChI=1/C11H11NO2/c1-13-10-4-7-3-8(6-12)9(7)5-11(10)14-2/h4-5,8H,3H2,1-2H3

Upstream product

• 84452-13-1 7-Chloro-3,4-dimethoxy-bicyclo[4.2.0]octa-1⁽⁶⁾,2,4-triene 
• 7721-62-2 4,5-dimethoxy-2-methylbenzaldehyde 
• 84452-08-4 1-Dichloromethyl-4,5-dimethoxy-2-methyl-benzene 
• 35249-62-8 3-(2-bromo-4,5-dimethoxyphenyl)propanenitrile 
• 1214788-46-1 (R)-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)nitrile 
• 1232191-48-8 2-(2-cyanoethyl)-4,5-dimethoxyphenyl dimethylsulphamate 
• 49621-56-9 3-(3,4-dimethoxyphenyl)propanenitrile 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 37629-85-9 (2E)-3-(3,4-dimethoxyphenyl)prop-2-enenitrile 
• 2859-78-1 4-Bromoveratrole 
• 53207-00-4 1-bromo-2-(bromomethyl)-4,5-dimethoxybenzene 
• 93-03-8 (3,4-dimethoxyphenyl)methanol 
• 55171-76-1 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-one 
• 38622-91-2 [(p-methylphenyl)sulfonylmethyl]isonitrile 

Downstream Products

• 54089-46-2 3-benzo[1,3]dioxol-5-yl-2-benzyl-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-4-carbonitrile 
• 96917-56-5 3,4-dimethoxy-7-(2-oxo-6-phenylsulfonyl-5E-hexenyl)bicyclo<4.2.0>octa-1(6),2,4-triene-7-carbonitrile 
• 96917-54-3 3,4-dimethoxy-7-<2-oxo-6,6-bis(phenylthio)hexyl>bicyclo<4.2.0>octa-1(6),2,4-triene-7-carbonitrile 
• 96917-57-6 (4aR,10S,10aS)-10-Benzenesulfonyl-6,7-dimethoxy-3-oxo-1,3,4,9,10,10a-hexahydro-2H-phenanthrene-4a-carbonitrile 
• 96917-57-6 (4aR,10R,10aR)-10-Benzenesulfonyl-6,7-dimethoxy-3-oxo-1,3,4,9,10,10a-hexahydro-2H-phenanthrene-4a-carbonitrile 
• 96917-59-8 C₂₅H₂₇NO₆S 
• 111674-94-3 3,4-dimethoxy-7-(2-oxo-6-phenylthio-5-hexenyl)bicyclo<4.2.0>octa-1(6),2,4-triene-7-carbonitrile 
• 111674-93-2 3,4-dimethoxy-7-<(2-oxo-6-phenylsulfinyl-6-phenylthio)hexyl>bicyclo<4.2.0>octa-1(6),2,4-triene-7-carbonitrile 
• 96917-55-4 3,4-dimethoxy-7-(2-oxo-6-phenylsulfinyl-6-phenylsulfonylhexyl)bicyclo<4.2.0>octa-1(6),2,4-triene-7-carbonitrile 
• 111674-95-4 (4aS,10aR)-6,7-Dimethoxy-3-oxo-10-phenylsulfanyl-1,3,4,9,10,10a-hexahydro-2H-phenanthrene-4a-carbonitrile 
• 111674-95-4 (4aS,10R,10aS)-6,7-Dimethoxy-3-oxo-10-phenylsulfanyl-1,3,4,9,10,10a-hexahydro-2H-phenanthrene-4a-carbonitrile 
• 111674-95-4 (4aS,10S,10aS)-6,7-Dimethoxy-3-oxo-10-phenylsulfanyl-1,3,4,9,10,10a-hexahydro-2H-phenanthrene-4a-carbonitrile 
• 111674-96-5 3,3-ethylenedioxy-1,2,3,4,4a,9,10,10aβ-octahydro-6,7-dimethoxy-10α-phenylthiophenanthrene-4aβ-carbonitrile 
• 111674-96-5 3,3-ethylenedioxy-1,2,3,4,4a,9,10,10aβ-octahydro-6,7-dimethoxy-10β-phenylthiophenanthrene-4aβ-carbonitrile 

Relevant articles and documents

Process for the enzymatic synthesis of (7S)-3,4-dimethoxybicyclo[4.2.0]OCTA-1,3,5-triene-7-carboxylic acid and application in the synthesis of ivabradine and salts thereof

Process for the enzymatic synthesis of the compound of formula (I): comprising enantioselective enzymatic hydrolysis of the nitrile of formula (IV): using the nitrilase of Rhodococcus rhodochrous of EMBL accession number EF467367.1, and the application of such a process in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid.

PROCESS FOR THE SYNTHESIS OF 3-(2-BROMO-4,5-DIMETHOXYPHENYL)PROPANENITRILE, AND APPLICATION IN THE SYNTHESIS OF IVABRADINE AND ADDITION SALTS THEREOF WITH A PHARMACEUTICALLY ACCEPTABLE ACID

Process for the synthesis of the compound of formula (I): Application in the synthesis of ivabradine, addition salts thereof with a pharmaceutically acceptable acid and hydrates thereof.

PROCESS FOR THE SYNTHESIS OF (2E)-3-(3,4-DIMETHOXYPHENYL)PROP-2-ENENITRILE, AND APPLICATION IN THE SYNTHESIS OF IVABRADINE AND ADDITION SALTS THEREOF WITH A PHARMACEUTICALLY ACCEPTABLE ACID

Process for the synthesis of the compound of formula (I): Application in the synthesis of ivabradine, addition salts thereof with a pharmaceutically acceptable acid and hydrates thereof.

PROCESS FOR THE SYNTHESIS OF 3-(2-BROMO-4,5-DIMETHOXYPHENYL)PROPANENITRILE, AND APPLICATION IN THE SYNTHESIS OF IVABRADINE AND ADDITION SALTS THEREOF WITH A PHARMACEUTICALLY ACCEPTABLE ACID

Process for the synthesis of the compound of formula (I): Application in the synthesis of ivabradine, addition salts thereof with a pharmaceutically acceptable acid and hydrates thereof.

Process for the synthesis of 3,4-dimethoxybicyclo[4.2.0]OCTA-1,3,5-triene-7-carbonitrile, and application in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid

Process for the synthesis of the compound of formula (I): Application in the synthesis of ivabradine, addition salts thereof with a pharmaceutically acceptable acid and hydrates thereof.

INDUSTRIAL PROCESS FOR THE SYNTHESIS OF IVABRADINE SALTS

Process for the synthesis of Ivabradine salts of formula (I) the chemical name of which is: 3-{3-[((S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene- 7-ylmethyl)-methyl-amino]-propyl}-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2-one salts (HQ=HCl, HBr, HI, HNO3, HClO4, (COOH)2), and new intermediates thereof. Certain crystalline forms of the acid addition salts of Ivabradine (I) with nitric acid (I, HQ=HNO3), hydrobromic acid (I, HQ=HBr), hydroiodic acid (I, HQ=HI), oxalic acid (I, HQ= (COOH)2) and perchloric acid (I, HQ=HClO4)).

Process for the resolution of enantiomers of (3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl) nitrile and application in the synthesis of ivabradine

Process for the optical resolution of the compound of formula (I): by chiral chromatography. Application in the synthesis of ivabradine, of its addition salts with a pharmaceutically acceptable acid and of their hydrates.

Process for the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid

Process for the synthesis of ivabradine of formula (I): and addition salts thereof with a pharmaceutically acceptable acid.

A practical synthesis of 1-cyano-4,5-dimethoxybenzocyclobutene

A practical synthesis of 1-cyano-4,5-dimethoxybenzocyclobutene, the key intermediate of Ivabradine, was developed in four or five steps using two different routes. 2-Bromo-4,5-dimethoxyhydrocinnamonitrile was produced via the condensation of 2-bromo-4,5-dimethoxybenzaldehyde with acetonitrile or cyanoacetic acid and reduction by NaBH4. Cyclisation gave 1-cyano-4,5-dimethoxybenzocyclobutene. Overall yields of the routes A and B were 30% and 37% respectively. Route B is a short and simple route, permitting the synthesis of 1-cyano-4,5-dimethoxybenzocyclobutene on a large scale.

FORMATION OF SUBSTITUTED BENZOCYCLOBUTENES THROUGH FLASH VACUUM PYROLYSIS

Benzocyclobutenes carrying a substituent in the four membered ring are obtained in high yield from 2-methyl benzaldehydes through a reaction sequence involving a pyrolitic 1,4-elimination of HCl in the crucial step.