1026016-83-0

Basic information

• Product Name: 2H-Benzo[a]quinolizin-2-one, 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-, (3R,11bR)-
• Synonyms: 2H-Benzo[a]quinolizin-2-one, 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-, (3R,11bR)-;(3R,11bR)-1,3,4,6,7,11b-Hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-one;(+)-Tetrabenazine;(3R,11bR)-3-Isobutyl-9,10-dimethoxy-3,4,6,7-tetrahydro-1H-pyrido[2,1-a]isoquinolin-2(11bH)-one;(3R,11bR)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one;(+)-Tetrabenazine (TBZ)
• CAS NO: 1026016-83-0
• Molecular Formula: C19H27NO3
• Molecular Weight: 317.42258
• Product Categories: APIs
• Mol File: 1026016-83-0.mol
• Article Data: 16

Chemical Properties

• Melting Point: 108-110 °C
• Boiling Point: 448.9 °C at 760 mmHg
• Flash Point: 225.3 °C
• Appearance: /
• Density: 1.12
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Chloroform (Slightly), Dichloromethane (Slightly), Ethyl Acetate (Slightly)
• PKA: 6.46±0.40(Predicted)
• CAS DataBase Reference: 2H-Benzo[a]quinolizin-2-one, 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-, (3R,11bR)-(CAS DataBase Reference)
• NIST Chemistry Reference: 2H-Benzo[a]quinolizin-2-one, 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-, (3R,11bR)-(1026016-83-0)
• EPA Substance Registry System: 2H-Benzo[a]quinolizin-2-one, 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-, (3R,11bR)-(1026016-83-0)

Safety Data

• Hazardous Substances Data: 1026016-83-0(Hazardous Substances Data)

Usage

Uses

(3R,11bR)-Tetrabenazine is an isomer of Tetrabenazine (T284000), a dopamine depleting agent, an antidyskinetic and antipsychotic.

Definition

ChEBI: A 9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one in which both stereocentres have R configuration.

Upstream product

• 58-46-8 (3R^*,11bR^*)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzoquinolizin-2-one 
• 1091627-89-2 (R)-tert-butyl 6,7-dimethoxy-1-(5-methyl-3-methylene-2-oxohexyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1223399-57-2 (3R,11bR)-tetrabenazine D-camphorsulfonate 
• 35963-20-3 (R)-10-camphorsulfonic acid 
• 718635-93-9 tetrabenazine 
• 718635-93-9 (3RS,11bRS)-tetrabenazine 
• 1228458-10-3 (2R,3S,11bR)-2-hydroxy-3-isobutyl-9,10-dimethoxy-2,3,6,7-tetrahydro-1H-pyrido[2,1-α]isoquinolin-4(11bH)-one 
• 1314098-76-4 N-(tert-butoxycarbonyl)-2-(2-iodo-4,5-dimethoxyphenyl)ethylamine 
• 1384186-28-0 N-2-(2-iodo-4,5-dimethoxyphenyl)ethyl-tert-butoxycarbonylacetamide 
• 1384186-18-8 2-(4,5-dimethoxy-2-vinylphenyl)ethanamine 
• 1384186-22-4 (2S,3R)-3-((tert-butyldimethylsilyl)oxy)-N-(2-iodo-4,5-dimethoxyphenethyl)-2-isobutylpent-4-enamide 
• 1384186-21-3 (2S,3R)-3-((tert-butyldimethylsilyl)oxy)-N-(4,5-dimethoxy-2-vinylphenethyl)-2-isobutylpent-4-enamide 
• 646-07-1 4-Methylpentanoic acid 
• 93-17-4 3,4-dimethoxyphenylacetonitrile 

Downstream Products

• 924854-60-4 (+)-β-DHTBZ 
• 862377-27-3 (2S,3S,11bR)-1,3,4,6,7,11b-hexahydro-9,10-methoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-ol 
• 862377-31-9 (2R,3S,11bR)-1,3,4,6,7,11b-hexahydro-9,10-methoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-ol 
• 1639208-54-0 (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-yl (S)-2-amino-3-methylbutanoate di(4-methylbenzenesulfonate) 
• 1025504-45-3 (S)-2-amino-3-methylbutyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolizin-2-yl ester 
• 1025504-76-0 (S)-2-benzyloxycarbonyl-amino-3-methylbutyric acid-(2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester 
• 1147130-19-5 C₂₉H₄₁NO₄ 
• 1147130-24-2 C₂₈H₃₉NO₆S 
• 1147130-21-9 C₂₉H₄₁NO₆S 

Relevant articles and documents

A concise total synthesis of (+)-tetrabenazine and (+)-α- dihydrotetrabenazine

Highly concise asymmetric total syntheses of (+)-tetrabenazine (1), a drug for the treatment of chorea associated with Huntington's disease, and of (+)α-dihydrotetrabenazine (2), an active metabolite of 1, have been accomplished. Our synthetic route features a trans-selective enol etherification, followed by an unprecedented cation-dependent aza-Claisen rearrangement to establish the carbon framework and two stereogenic centers of tetrabenazine. The syntheses consist of seven steps (34% overall yield) for (+)-2 and eight steps (22% overall yield) for (+)-l.

Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors

Tetrabenazine (TBZ) ((±)-1) and dihydrotetrabenazines (DHTBZ) are potent inhibitors of VMAT2. Herein, a practical chemical resolution of (±)-1 and stereoselective synthesis of all eight DHTBZ stereoisomers are described. The result of VMAT2 binding assay revealed that (+)-1 (Ki = 4.47 nM) was 8000-fold more potent than (-)-1 (Ki = 36,400 nM). Among all eight DHTBZ stereoisomers, (2R,3R,11bR)-DHTBZ ((+)-2: Ki = 3.96 nM) showed the greatest affinity for VMAT2. The (3R,11bR)-configuration appeared to play a key role for VMAT2 binding. In summary, (+)-1, (+)-2, and their derivatives warrant further studies in order to develop more potent and safer drugs for the treatment of chorea associated with Huntington's disease and other hyperkinetic disorders.

Dynamic resolution method of tetrabenazine

The invention provides a dynamic resolution method of tetrabenazine, and belongs to the field of medicinal chemical industry. The method can be used for resolving tetrabenazine to obtain (3R,11bR)-tetrabenazine. The method comprises the following steps: mixing and reacting a resolving reagent is with tetrabenazine to obtain a desired configuration, performing separation, and then carrying out alkali dissociation to obtain the (3R,11bR)-tetrabenazine. The analytical method can effectively separate tetrabenazine, and has the advantages of high product purity, high yield, simplicity in operationand solvent recoverability.

CRYSTALLINE VALBENAZINE FREE BASE

The present disclosure generally relates to crystalline valbenazine. The present disclosure also generally relates to a pharmaceutical composition comprising crystalline valbenazine, as well of methods of using crystalline valbenazine in the treatment of