57849-23-7

Usage

Uses

Used in Medicinal Chemistry and Pharmaceutical Research:
()-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline is used as a building block for the synthesis of various bioactive molecules. Its unique structure and functional groups enable the development of compounds with potential therapeutic applications.
Used in the Development of New Drugs for Pain Treatment:
()-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline has potential applications in the development of new drugs for the treatment of pain. Its pharmacological and neurological activity make it a promising candidate for the design of pain-relieving medications.
Used in the Development of New Drugs for Addiction Treatment:
()-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline can be utilized in the development of new drugs for addiction treatment. Its interaction with neurotransmitter receptors and biological targets may contribute to the creation of effective treatments for various forms of addiction.
Used in the Development of New Drugs for Psychiatric Disorders:
()-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline also has potential applications in the development of new drugs for the treatment of psychiatric disorders. Its ability to target specific biological pathways and receptors may lead to the discovery of novel therapeutic agents for mental health conditions.

Upstream product

• 74570-02-8 4-((R)-1,2,3,4,5,6,7,8-octahydro-[1]isoquinolylmethyl)-phenol 
• 104-01-8 4-Methoxyphenylacetic acid 
• 3399-73-3 2-(1-cyclohexenyl)ethylamine 
• 51072-34-5 N-(2-cyclohex-1-enylethyl)-2-(4-methoxyphenyl)-acetamide 
• 51072-35-6 1-(4-methoxybenzyl)-3,4,5,6,7,8-hexahydro-isoquinoline 
• 100466-49-7 ((S)-1-tert-Butoxymethyl-2-methyl-propyl)-[1-[(S)-1-(4-methoxy-benzyl)-3,4,5,6,7,8-hexahydro-1H-isoquinolin-2-yl]-meth-(E)-ylidene]-amine 
• 74570-02-8 4-((S)-1,2,3,4,5,6,7,8-octahydro-[1]isoquinolylmethyl)-phenol 
• 2721-62-2 1,2,3,4,5,6,7,8-octahydroisoquinoline 
• 51072-36-7 (+)-1-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline 
• 94992-57-1 (R)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline L-mandelate 
• 30356-08-2 (S)-1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxyphenyl)methyl]isoquinoline 
• 38969-65-2 1-(p-methoxybenzyl)-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline 
• 93477-35-1 (+/-)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline hydrobromide 
• 221191-51-1 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline formate 

Downstream Products

• 806596-93-0 4-(5,6,7,8-tetrahydro-[1]isoquinolylmethyl)-phenol 
• 101877-59-2 (4-methoxy-phenyl)-(5,6,7,8-tetrahydro-[1]isoquinolyl)-ketone 
• 109601-25-4 (4-methoxy-phenyl)-(5,6,7,8-tetrahydro-[1]isoquinolyl)-methanol 
• 102890-44-8 1-(4-methoxy-benzyl)-5,6,7,8-tetrahydro-isoquinoline-2-oxide 
• 101729-49-1 1-(4-acetoxy-benzyl)-5,6,7,8-tetrahydro-isoquinoline 
• 102178-07-4 1-(α-acetoxy-4-methoxy-benzyl)-5,6,7,8-tetrahydro-isoquinoline 
• 98237-33-3 1-(4-Methoxybenzyl)-2-methyl-5,6,7,8-tetrahydroisochinoliniumiodide 
• 124106-42-9 2-benzyl-1-(4-methoxy-benzyl)-5,6,7,8-tetrahydro-isoquinolinium; bromide 
• 124140-86-9 1-(4-acetoxy-benzyl)-2-benzyl-5,6,7,8-tetrahydro-isoquinolinium; bromide 
• 118647-01-1 (+/-)-2-benzyl-1-(4-methoxy-benzyl)-1,2,3,4,5,6,7,8-octahydro-isoquinoline 
• 98985-27-4 rac-3-benzyloxy-17-methyl-morphinane 
• 102558-09-8 (+/-)-4-(2-benzyl-1,2,3,4,5,6,7,8-octahydro-[1]isoquinolylmethyl)-phenol 

Relevant academic research and scientific papers

Racemization recovery method of dextromethorphan hydrobromide intermediate byproducts

A racemization recovery method of dextromethorphan hydrobromide intermediate byproducts comprises the following steps: 1) performing mother liquor treatment: under a stirring condition, carrying out reduced pressure distillation until methanol is basically evaporated completely, when the temperature of the concentrated mother liquor is lower than 40 DEG C, adding a sodium hydroxide solution, stirring, standing, detecting that the pH value is greater than 12, layering, recovering mandelic acid by using the obtained water phase, concentrating the obtained oil phase under reduced pressure until toluene is completely evaporated, and cooling to 65-80 DEG C; 2) performing N-chlorination: adding isopropanol, and dropwise adding a sodium hypochlorite solution; 3) performing racemization: adding liquid caustic soda into the reaction system, and stirring for reaction; 4) reducing: dropwise adding a sodium borohydride solution, and reacting completely; 5) performing chiral resolution: adding methanol and D-mandelic acid into the toluene solution of a compound (I), and carrying out chiral resolution; and (6) refining the mother liquor: treating the mother liquor obtained in step (5) as a raw material according to the treatment methods in steps (1)-(4) to obtain a mother liquor prepared compound (I) methylbenzene solution, and adding oxalic acid for refining.

Asymmetric Synthesis of a Key Dextromethorphan Intermediate and Its Analogues Enabled by a New Cyclohexylamine Oxidase: Enzyme Discovery, Reaction Development, and Mechanistic Insight

(S)-1-(4-Methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline [(S)-1-(4-methoxybenzyl)-OHIQ, (S)-1a] is a key synthetic intermediate in the industrial production of dextromethorphan, one of the most widely used over-the-counter antitussives. We report here that a new cyclohexylamine oxidase discovered by genome mining, named CHAOCCH12-C2, was able to completely deracemize 100 mM 1a under Turner's deracemization conditions to afford (S)-1a in 80% isolated yield and 99% ee at a semipreparative scale (0.4 mmol). When this biocatalytic reaction was scaled up to a gram scale (5.8 mmol), without reaction optimization (S)-1a was still isolated in 67% yield and 96% ee. The relatively higher kcat determined for CHAOCCH12-C2 was rationalized as one major factor rendering this enzyme capable of oxidizing 1a effectively at elevated substrate concentrations. Protein sequence alignment, analysis of our co-crystal structure of CHAOCCH12-C2 complexed with the product 1-(4-methoxybenzyl)-3,4,5,6,7,8-hexahydroisoquinoline [1-(4-methoxybenzyl)-HHIQ, 2a], and the structure-guided mutagenesis study together indicated L295 is one of the critical residues for this efficient enzymatic oxidation process and supported the presence of two cavities as well as a catalytically important "aromatic cage" formed by F342, Y433, and FAD. The synthetic applicability of CHAOCCH12-C2 was further underscored by the stereoselective synthesis of various enantioenriched 1-benzyl-OHIQ derivatives of potential pharmaceutical importance at a semipreparative scale.

Imine Reductase-Catalyzed Enantioselective Reduction of Bulky α,β-Unsaturated Imines en Route to a Pharmaceutically Important Morphinan Skeleton

The morphinan skeleton is an important sub-structure in many medicines such as dextromethorphan, and can be constructed from 1-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline (1-benzyl-OHIQ) derivatives. 1-Benzyl-3,4,5,6,7,8-hexahydroisoquinolines (1-benzyl-HHIQs), the precursors of 1-benzyl-OHIQs, constitute a type of bulky α, β-unsaturated imines. Until now, the application of imine reductases (IREDs) to α, β-unsaturated imines has only rarely been reported. In this study, through evaluation of 48 IREDs, both enantiomers of 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (1-(4-methoxybenzyl)-OHIQ) were obtained in high yield and excellent optical purity. Among the enzymes, the most steric hindrance-tolerant IRED from Sandarearacinus amylolyticus (IR40) was able to convert various phenyl substituted 1-benzyl-HHIQ to the corresponding 1-benzyl-OHIQ derivatives with excellent enantiometric excess. These results provide an effective route to synthesize these important compounds via enantioselective reduction of bulky α, β-unsaturated imine precursors, which can be readily prepared from 2-(1-cyclohexenyl)ethylamine and corresponding aryl acetic acids. (Figure presented.).

A (S) or (R)- 1 - (4 - methoxybenzyl) - 1, 2, 3, 4, 5, 6, 7, 8 - quinoline of eight hydrogens different preparation method

The invention discloses a preparation method of (S) or (R)-1-(4-methoxy benzyl)-1,2,3,4,5,6,7,8-octahydro isoquinoline acetate, wherein the method includes the steps: (1) mixing an aromatic solution of a compound having a structure represented by the formula III with acetic acid, to obtain a solution 1; (2) adding a (S)-1-(4-methoxy benzyl)-1,2,3,4,5,6,7,8-octahydro isoquinoline acetate seed crystal or a (R)-1-(4-methoxy benzyl)-1,2,3,4,5,6,7,8-octahydro isoquinoline acetate seed crystal into the solution 1, to obtain a solution 2; and (3) cooling the solution 2 to 0-5 DEG C, crystallizing to obtain (S)-1-(4-methoxy benzyl)-1,2,3,4,5,6,7,8-octahydro isoquinoline acetate or (R)-1-(4-methoxy benzyl)-1,2,3,4,5,6,7,8-octahydro isoquinoline acetate.

Method for preparing (S)-1-(4-methoxy benzyl)-1, 2, 3, 4, 5, 6, 7, 8-octahydro isoquinoline

The invention discloses a method for preparing (S)-1-(4-methoxy benzyl)-1, 2, 3, 4, 5, 6, 7, 8-octahydro isoquinoline which is a dextromethorphan intermediate. The method includes selectively hydrogenating 1-(4-methoxy benzyl)-3, 4, 5, 6, 7, 8-octahydro isoquinoline (II) under the condition of (R)-N-(5-fluorine-2-hydroxyl benzyl)-2-methylpropane-2-sulfinamide and trichlorosilane to obtain the (S)-1-(4-methoxy benzyl)-1, 2, 3, 4, 5, 6, 7, 8-octahydro isoquinoline (I). The 1-(4-methoxy benzyl)-3, 4, 5, 6, 7, 8-octahydro isoquinoline (II) is used as a raw material, and the (R)-N-(5-fluorine-2-hydroxyl benzyl)-2-methylpropane-2-sulfinamide is used as an organic chiral ligand. The method has the advantages that the organic chiral ligand is used, and the raw material is inexpensive, safe, simpleand easily available; the reaction temperatures range from -20 DEG C to -15 DEG C, and accordingly the method can be implemented in industrial production; an ee (enantiomeric excess) value of the (S)-1-(4-methoxy benzyl)-1, 2, 3, 4, 5, 6, 7, 8-octahydro isoquinoline which is a product can reach 63%.

Method for preparing levallorphan tartrate

The invention provides a method for preparing levallorphan tartrate and belongs to the technical field of drug and chemical synthesis. The method takes methoxyphenylacetic acid and 2-(cyclohexenyl)ethylamine as initial raw materials, and comprises nine reaction steps such as acylation condensation, Bischler-Napieralski ring formation reaction, imine reduction, ether bond hydrolysis, resolution, N-alkylation, Grewe cyclization reaction, and salifying. According to the method, the levallorphan tartrate and each intermediate can be obtained at high yield and high purity, and the method can serve as an industrial method for performing large-scale production.

AN IMPROVED PROCESS FOR THE PREPARATION OF BUTORPHANOL TARTRATE

The present invention relates to an improved process for the preparation of Butorphanol tartrate of formula (I),

A process for preparing dextromethorphan method

The invention relates to a novel method for preparing dextromethorphan. When the method is used for preparing an intermediate (+)-1-(4-methoxy) benzyl-1,2,3,4,5,6,7,8-hexahydroisoquinoline (VI), a catalytic reducing method is adopted to carry out chiral reduction on 1-(4-methoxy) benzyl-3,4,5,6,7,8-hexahydroisoquinoline (VI), so that the intermediate is prepared with high selectivity. The novel method disclosed by the invention can cancel complex operations such as chiral resolution, is simple to operate, gentle in reaction condition, short in total time, wide in material source, and very suitable for industrially producing dextromethorphan.

Racemization recycling method for byproduct in resolution mother liquor of dextromethorphan hydrobromide midbody

The invention relates to a racemization recycling method for a resolution byproduct in a dextromethorphan hydrobromide midbody 1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxy phenyl) methyl] isoquinoline. The racemization recycling method is characterized by comprising the following steps: (1) resolving racemic 1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxy phenyl) methyl] isoquinoline by using D-mandelic acid or D-tartaric acid so as to obtain D-mandelic acid or D-tartrate and 1,2,3,4,5,6,7,8-octahydro-R-1-[(4-methoxy phenyl) methyl] isoquinoline of a 1,2,3,4,5,6,7,8-octahydro-S-1-[(4-methoxy phenyl) methyl] isoquinoline compound; (2) oxidizing the 1,2,3,4,5,6,7,8-octahydro-R-1-[(4-methoxy phenyl) methyl] isoquinoline so as to obtain 1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxy phenyl) methyl] isoquinoline; (3) reducing the 1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxy phenyl) methyl] isoquinoline, thereby obtaining the dextromethorphan midbody 1,2,3,4,5,6,7,8-octahydro-1-[(4-methoxy phenyl) methyl] isoquinoline. The racemization recycling method for the byproduct, namely, a levogyration midbody of dextromethorphan, is gentle in condition, simple and convenient to operate and small in material consumption.

COMPOSITIONS AND METHODS FOR THE TREATMENT OF RESPIRATORY DISORDERS

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of respiratory disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of cough caused by minor throat and bronchial irritation (such as commonly accompanies the flu and common cold), as well as those resulting from inhaled particle irritants, upper respiratory infections, (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis, neuropathic pain and pain associated with fibromyalgia.