85175-67-3

Basic information

• Product Name: Zatebradine
• Synonyms: Zatebradine
• CAS NO: 85175-67-3
• Molecular Formula: C₂₆H₃₆N₂O₅
• Molecular Weight: 456.579
• Mol File: 85175-67-3.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 612.5°C at 760 mmHg
• Flash Point: 324.3°C
• Appearance: /
• Density: 1.115g/cm³
• Vapor Pressure: 6.09E-15mmHg at 25°C
• Refractive Index: 1.545
• Storage Temp.: 2-8°C
• PKA: 8.99±0.50(Predicted)
• CAS DataBase Reference: Zatebradine(CAS DataBase Reference)
• NIST Chemistry Reference: Zatebradine(85175-67-3)
• EPA Substance Registry System: Zatebradine(85175-67-3)

Safety Data

• Hazardous Substances Data: 85175-67-3(Hazardous Substances Data)

Usage

Originator

ZATEBRADINE HYDROCHLORIDE,Boenhringer Ingelheim

Manufacturing Process

A suspension of 1-[7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl]-3- (N-benzylmethylamino)propane and 10% palladium-on-charcoal in glacial acetic acid was hydrogenated at 50°C and at a hydrogen pressure of 5 bar. After the catalyst had been filtered off, the solvent was evaporated in vacuum, and the residue was taken up in methylene chloride. After the solution had been extracted with an aqueous sodium bicarbonate solution and washed with water, it was dried over magnesium sulfate, evaporated and purified over silica gel with methylene chloride and then with increasing amounts of methanol (up to 10%). The N-[3-(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3- benzazepin-2-one-3-yl)propyl]methylamine hydrochloride. Yield: 87% of theory. Melting point: 110°C (dec.). 1.26 g (20 mmols) of sodium cyanoborohydride were added to a solution of 3.29 g (10 mmols) of N-[3-(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3- benzazepin-2-one-3-yl)propyl]methylamine hydrochloride and 1.8 g (10 mmol) of 2-(3,4-dimethoxyphenyl)acetaldehyde in 40 ml of ethanol, while maintaining a pH of 6-7 by the addition of 2 N hydrochloric acid, and stirring was continued for 48 h at room temperature. After evaporating the solution in vacuum, the residue was taken up in dilute hydrochloric acid and extracted twice with ether. Subsequently, the aqueous phase was made alkaline and extracted three times with methylene chloride, and the organic phase was evaporated and purified on silica gel. The 1-[7,8-dimethoxy-1,3,4,5- tetrahydro-2H-3-benzazepin-2-on-3-yl]-3-[N-methyl-N-(2-{3,4- dimethoxyphenyl}ethyl)amino]propane was obtained.

Therapeutic Function

Bradycardic

InChI:InChI=1/C26H36N2O5/c1-27(13-9-19-7-8-22(30-2)23(15-19)31-3)11-6-12-28-14-10-20-16-24(32-4)25(33-5)17-21(20)18-26(28)29/h7-8,15-17H,6,9-14,18H2,1-5H3

Upstream product

• 50-00-0 formaldehyd 
• 85175-76-4 1-[7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl]-3-[N-(2-{3,4-dimethoxy-phenyl}-ethyl)-amino]-propane 
• 10313-60-7 3,4-dimethoxyphenylacetyl chloride 
• 73954-34-4 N-(2,2-dimethoxy-ethyl)-3,4-dimethoxyphenylacetamide 
• 85175-59-3 3-(3-chloropropyl)-1,3-dihydro-7,8-dimethoxy-2H-3-benzazepine-2-one 
• 73942-87-7 7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one 
• 93-40-3 (3,4-Dimethoxyphenyl)acetic acid 
• 596093-60-6 2-benzyl-6,7-dimethoxy-1-tribromomethyl-1,2,3,4-tetrahydro-isoquinoline 
• 596093-62-8 3-benzyl-1-hydroxy-7,8-dimethoxy-1,3,4,5-tetrahydro-benzo[d]azepin-2-one 
• 596093-63-9 1-hydroxy-7,8-dimethoxy-1,3,4,5-tetrahydro-benzo[d]azepin-2-one 
• 5096-82-2 benzyl-6,7-dimethoxy-3,4-dihydroisoquinolin-2-ium hydrobromide 
• 3382-18-1 6,7-dimethoxy-3,4-dihydro-isoquinoline 
• 3490-06-0 N-methylhomoveratrylamine 
• 36770-74-8 N-(3-chloropropyl)-3,4-dimethoxy-N-methylphenethylamine 

Relevant articles and documents

Silver nitrate-promoted ring enlargement of 1-tribromomethyl-1,2-dihydro- and 1-tribromomethyl-1,2,3,4-tetrahydro-isoquinoline derivatives: Application to the synthesis of the anti-anginal zatebradine

The one step AgNO3-mediated ring enlargement of 1-tribromomethyl-1,2-dihydro- and 1-tribromomethyl-1,2,3,4-tetrahydro-isoquinoline derivatives into 1,2-dihydro- and 1,2,3,4-tetrahydro-benzo[d]azepin-2-ones, respectively, is reported. This reaction offers a convenient entry to potentially active substances such as the anti-anginal zatebradine.

Benzazepine derivatives, their pharmaceutical compositions and method of use

Compounds of the formula STR1 wherein A is --CH2 --CH2 --, --CH=CH--, --NH--CO--, --CH2 --CO-- or STR2 where R7 is alkyl of 1 to 3 carbon atoms, and B is methylene, carbonyl or thiocarbonyl, or A is --CO--CO--, --N=CH--, STR3 where R8 is hydrogen or alkyl of 1 to 3 carbon atoms substituted by a phenyl, methoxyphenyl or dimethoxyphenyl, and B is methylene; E is n-alkylene of 2 to 4 carbon atoms optionally substituted by an alkyl of 1 to 3 carbon atoms, 2-hydroxy-n-propylene, 2-hydroxy-n-butylene or 3-hydroxy-n-butylene; G is n-alkylene of 1 to 5 carbon atoms optionally substituted by an alkyl of 1 to 3 carbon atoms, wherein one methylene group of an n-alkylene of 2 to 5 carbon atoms can be replaced by a carbonyl group, with the proviso that B represents a methylene or carbonyl group, or methylene-n-hydroxy-alkylene of 1 to 4 carbon atoms, where the methylene group is attached to the nitrogen atom; and R1 to R5 are simple substituents of various types; and non-toxic, pharmacologically acceptable acid addition salts thereof. The compounds as well as their salts are useful as bradycardiacs.