1169801-28-8

Basic information

• Product Name: (S)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-1,2,3,4-tetrahydroisoquinoline acetate
• Synonyms: (S)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-1,2,3,4-tetrahydroisoquinoline acetate
• CAS NO: 1169801-28-8
• Molecular Weight: 425.448
• Mol File: 1169801-28-8.mol
• Article Data: 6

Chemical Properties

• CAS DataBase Reference: (S)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-1,2,3,4-tetrahydroisoquinoline acetate(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-1,2,3,4-tetrahydroisoquinoline acetate(1169801-28-8)
• EPA Substance Registry System: (S)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-1,2,3,4-tetrahydroisoquinoline acetate(1169801-28-8)

Safety Data

• Hazardous Substances Data: 1169801-28-8(Hazardous Substances Data)

Upstream product

• 769172-81-8 (S)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-1,2,3,4-tetrahydroisoquinoline 
• 64-19-7 acetic acid 
• 64-18-6 formic acid 
• 1169801-32-4 6,7-dimethoxy-1-[2-(4-trifluoromethyl-phenyl)-ethyl]-3,4-dihydro-isoquinoline methanesulfonic acid salt 
• 769172-66-9 N-[2-(3,4-dimethoxy-phenyl)-ethyl]-3-(4-trifluoromethyl-phenyl)-propionamide 

Downstream Products

• 769172-81-8 (S)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-1,2,3,4-tetrahydroisoquinoline 
• 913358-93-7 almorexant hydrochloride 

Relevant articles and documents

Catalytic Asymmetric Reduction of a 3,4-Dihydroisoquinoline for the Large-Scale Production of Almorexant: Hydrogenation or Transfer Hydrogenation?

Several methods are presented for the enantioselective synthesis of the tetrahydroisoquinoline core of almorexant (ACT-078573A), a dual orexin receptor antagonist. Initial clinical supplies were secured by the Noyori Ru-catalyzed asymmetric transfer hydrogenation (Ru-Noyori ATH) of the dihydroisoquinoline precursor. Both the yield and enantioselectivity eroded upon scale-up. A broad screening exercise identified TaniaPhos as ligand for the iridium-catalyzed asymmetric hydrogenation with a dedicated catalyst pretreatment protocol, culminating in the manufacture of more than 6 t of the acetate salt of the tetrahydroisoquinoline. The major cost contributor was TaniaPhos. By switching the dihydroisoquinoline substrate of the Ru-Noyori ATH to its methanesulfonate salt, the ATH was later successfully reduced to practice, delivering several hundreds of kilograms of the tetrahydroisoquinoline, thereby reducing the catalyst cost contribution significantly. The two methods are compared with regard to green and efficiency metrics.

TRISUBSTITUTED 3,4-DIHYDRO-1H-ISOQUINOLIN COMPOUND, PROCESS FOR ITS PREPARATION, AND ITS USE

The present invention relates to the compound of formula 7*acetate (see below), a process for its preparation, and its use

PROCESS FOR THE PREPARATION OF AN ENANTIOMERIC TRISUBSTITUTED 3,4-DIHYDRO-ISOQUINOLINE DERIVATIVE

The present invention relates to a process for the preparation of the compound of formula (7) which process comprises the hydrogenation of the compound of formula (4) using bis[chloro-1,5-cyclooctadiene-iridium], (S)-i -dicyclohexylphosphino- 2-[(S)-α-(di