91797-57-8

Usage

Uses

Used in Pharmaceutical Industry:
rac-cis-N-Desmethyl Sertraline Hydrochloride is used as a research compound for studying the properties and effects of Sertraline and its metabolites. This helps in understanding the differences in activity and potential applications in the development of new antidepressant medications.

InChI:InChI=1/C16H15Cl2N.ClH/c17-14-7-5-10(9-15(14)18)11-6-8-16(19)13-4-2-1-3-12(11)13;/h1-5,7,9,11,16H,6,8,19H2;1H/t11-,16-;/m0./s1

Upstream product

• 79560-19-3 4-(3,4-dichlorophenyl)-3,4-dihydro-2H-naphthalen-1-one 
• 124379-29-9 (4S)-4-(3,4-dichlorophenyl)-1-tetralone 
• 674767-90-9 C₂₀H₂₁Cl₂NOS 
• 1097616-52-8 N-((1S,4R)-1-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-4-yl)acetamide 
• 675126-11-1 (1R,4S)-N-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-formamide 
• 674768-15-1 (1S,4R)-N-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-formamide 

Downstream Products

• 1097616-52-8 N-((1S,4R)-1-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-4-yl)acetamide 

Relevant academic research and scientific papers

Processes for the Preparation of Dasotraline and Intermediates Thereof

The present invention provides processes for the preparation of Dasotraline (1), as well as intermediates useful in the preparation thereof. In particular, processes are provided for the production of the compound of Formula (2), or a salt thereof, and it

ENAMIDE PROCESS

A convenient method for converting oximes into enamides is disclosed. The process produces enamides without the concomitant production of a large volume of metallic waste. The enamides are useful precursors to amides and amines.

A chemoenzymatic approach to enantiomerically pure amines using dynamic kinetic resolution: application to the synthesis of norsertraline

Racemization catalyst 5c and the enzyme Candida antarctica lipase B were combined in a one-pot dynamic kinetic resolution (DKR) of primary amines in which a wide range of amines were transformed to their corresponding amides in up to 95% isolated yield and > 99% ee. The DKR protocol was applicable with either isopropyl acetate or dibenzyl carbonate as the acyl donor. In the latter case, release of the free amine from the carbamate products was carried out under very mild conditions. The racemization of (S)-1-phenylethylamine with several different Ru catalysts was also evaluated. Catalyst 5c, of the Shvo type, was able to selectively racemize amines and was also compatible with the reaction conditions used for DKR. A racemization study of three different amines with varying electronic properties was also performed. Competitive racemization of a 1:1 mixture of the deuterated and non-deuterated amine was carried out with 5c and a primary kinetic isotope effect was observed for all three amines, providing support that the rate-determining step is β-hydride elimination. The chemoenzymatic DKR protocol was applied to the synthesis of norsertraline (16) by using a novel route starting from readily available 1,2,3,4-tetrahydro- 1-naphthy lamine (1o).

A facile deprotection of secondary acetamides

(Chemical Equation Presented) Imidoyl chlorides, generated from secondary acetamides and oxalyl chloride, can be harnessed for a selective and practical deprotection sequence. Treatment of these intermediates with 2 equiv of propylene glycol and warming enables the rapid release of amine hydrochloride salts in good yields. Notably, the reaction conditions are mild enough to allow for a swift deprotection with no observed epimerization of the amino center.

PREPARATION OF CHIRAL AMIDES AND AMINES

This invention provides a convenient method for converting oximes into enamides. The process does not require the use of metallic reagents. Accordingly, it produces the desired compounds without the concomitant production of a large volume of metallic waste. The enamides are useful precursors to amides and amines. The invention provides a process to convert a prochiral enamide into the corresponding chiral amide. In an exemplary process, a chiral amino center is introduced during hydrogenation through the use of a chiral hydrogenation catalyst. In selected embodiments, the invention provides methods of preparing amides and amines that include the 1,2,3,4-tetrahydro-N-alkyl-1-naphthalenamine or 1,2,3,4-tetrahydro-1-naphthalenamine substructure.

COMBINATIONS OF ESZOPICLONE AND TRANS 4-(3,4-DICHLOROPHENYL)-1,2,3,4-TETRAHYDRO-N-METHYL-1-NAPTHALENAMINE OR TRANS 4-(3,4-DICHLOROPHENYL)-1,2,3,4-TETRAHYDRO-1-NAPTHALENAMINE, AND METHODS OF TREATMENT OF MENOPAUSE AND MOOD, ANXIETY, AND COGNITIVE DISORDERS

One aspect of the present invention relates to pharmaceutical compositions containing two or more active agents that when taken together can be used to treat, e.g., menopause, mood disorders, anxiety disorders, or cognitive disorders. The first component of the pharmaceutical composition is a sedative eszopiclone. The second component of the pharmaceutical composition is trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine. The present invention also relates to a method of treating menopause, perimenopause, mood disorders, anxiety disorders, and cognitive disorders.

TREATMENT OF PAIN DISORDERS WITH trans 4-(3,4-DICHLOROPHENYL)-1,2,3,4-TETRAHYDRO-1-NAPHTHALENAMINE AND ITS FORMAMIDE

Treatment of pain disorders with (1R,4S)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine; and (1S,4R)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine is disclosed. A process for preparing 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine is also disclosed. The process includes the preparation of all four isomers of N-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl]formamide, which are also useful in treatment of pain disorders.

Development of a large-scale stereoselective process for (1 R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride

A convenient, multikilogram-scale, stereoselective process for the synthesis of (1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride 1 is described. The key steps involve synthesis of sulflnyl imine (Rs,4S)-5 from (S)-tetralone (4S)-3 and (R)-tert-butylsulfinamide (Rs)-4, and its stereoselective reduction with 9-BBN to produce the (1R)-amine center of 1. The process has been scaled up to multikilogram scale and gives 1 in an overall yield of >50% with a chemical purity of 99.7 A% by HPLC and stereochemical purity of >99.9% by chiral HPLC.

TREATMENT OF CNS DISORDERS WITH TRANS 4-(3,4-DICHLOROPHENYL)-1,2,3,4-TETRAHYDRO-1-NAPTHALENAMINE AND ITS FORMAMIDE

Treatment of CNS disorders with (1R,4S)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine; and (1S,4R)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine is disclosed. A process for preparing 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine is also disclosed. The process includes the preparation of all four isomers of N-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl]formamide, which are also useful.