488787-59-3

Usage

Uses

Used in Cardiovascular Medicine:
(-)-4-[4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile is used as a beta blocker for the treatment of high blood pressure, angina pectoris, and certain types of irregular heart rhythms. It functions by inhibiting the effects of adrenaline on the heart and blood vessels, leading to a decrease in heart rate and blood pressure, which is beneficial for patients with these conditions.
Used in Post-Heart Attack Care:
(-)-4-[4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile is also used as a preventive measure to reduce the risk of recurrent heart attacks. It has been shown to improve survival rates in patients with heart failure, making it an essential component in the post-heart attack care regimen.
Used in Pharmaceutical Formulations:
(-)-4-[4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile is typically administered orally in the form of tablets or capsules, making it a convenient and accessible treatment option for patients requiring beta blocker therapy.

Upstream product

• 108-05-4 vinyl acetate 
• 103146-25-4 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile 
• 123-20-6 vinyl n-butyrate 
• 19070-16-7 3-(N,N-dimethylamino)propylmagnesium chloride 
• 75-98-9 Trimethylacetic acid 
• 260371-16-2 4-(4-fluorobenzoyl)-3-(hydroxymethyl)benzonitrile 
• 352-13-6 4-flourophenylmagnesium bromide 
• 128173-53-5 (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile hemi-(+)-di-(p-toluoyl) tartaric acid salt 
• 128173-53-5 4-(4-dimethylamino-1-(4'-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)-benzonitrile (+)-di-p-toluoyl-D-tartaric acid salt 
• 1370643-24-5 4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(tert-butyldimethylsiloxymethyl)benzonitrile 
• 411221-53-9 C₂₀H₂₁FN₂O₂ 
• 448-59-9 tris(4-fluorophenyl)boroxine 
• 190956-77-5 4-chloro-1-(2,4-dichlorophenyl)butan-1-one 
• 128173-53-5 (S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile (+)-di-p-toluoyltartaric acid salt 

Downstream Products

• 59729-33-8 1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran-5-carbonitrile 
• 219861-08-2 escitalopram oxalate 
• 878007-22-8 (S)-(-)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(2-nitro-4-chlorophenoxymethyl)benzonitrile hydrochloride 
• 863116-45-4 succinic acid mono-{5-cyano-2-[(S)-4-dimethylamino-1-(4-fluorophenyl)-1-hydroxybutyl]-benzyl} ester 
• 128196-01-0 escitalopram 

Relevant academic research and scientific papers

PRODUCTION METHOD OF (1S)-1-[3-(DIMETHYLAMINO)PROPYL]-1-(4-FLUOROPHENYL)-1,3-DIHYDROISOBENZOFURAN-5-CARBONITRILE OXALATE

PROBLEM TO BE SOLVED: To provide a (1S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (escitalopram) oxalate having extremely high optical purity and extremely little residual solvent. SOLUTION: The following production method is used: (1S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile oxalate, by 1 part by mass, is dissolved and heated in an organic solvent containing 8-15 parts by volume of ethanol, then the solution is cooled at a rate of at least 25°C/h or more to crystallize so as to obtain the oxalate as a crystallized product. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

PRODUCTION METHOD OF (1S)-4-[4-(DIMETHYLAMINO)-1-(4'-FLUOROPHENYL)-1-HYDROXYBUTYL]-3-(HYDROXYMETHYL)-BENZONITRILE HEMI(+)-DI-(p-TOLUOYL) TARTRATE, AND PRODUCTION METHOD OF (1S)-1-[3-(DIMETHYLAMINO)PROPYL]-1-(4-FLUOROPHENYL)-1,3-DIHYDROISOBENZOFURAN-5-CARBONITRILE AND SALT THEREOF USING THE TARTRATE

PROBLEM TO BE SOLVED: To provide a (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartrate having extremely high optical purity, and escitalopram having extremely high optical purity and its salt obtained from the above tartrate. SOLUTION: A production method is used, in which a crude (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartrate is recrystallized in a mixture solvent of alcohol and water, with the content of the water being 3.0 to 15.0 mass% in the mixture solvent of the alcohol and water, so as to obtain a recrystallized material of the above tartrate having extremely high optical purity. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

PRODUCTION METHOD OF S-4-[4-(DIMETHYLAMINO)-1-(4'-FLUOROPHENYL)-1-HYDROXYBUTYL]-3-(HYDROXYMETHYL)-BENZONITRILE, AND PRODUCTION METHOD OF (1S)-1-[3-(DIMETHYLAMINO)PROPYL]-1-(4-FLUOROPHENYL)-1,3-DIHYDROISOBENZOFURAN-5-CARBONITRILE AND SALT THEREOF USING THE COMPOUND

PROBLEM TO BE SOLVED: To provide a (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile having extremely high chemical purity and optical purity, and escitalopram having extremely high optical purity and its salt obtained from the above compound. SOLUTION: The following production method is used: (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartrate is made to react in a solvent comprising at least one sparingly water-soluble organic solvent selected from the group consisting of aromatic hydrocarbons and halogenated hydrocarbons, and water so as to obtain an educt of the tartrate. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

PROCESS FOR PRODUCING (1S)-4-[4-(DIMETHYLAMINO)-1-(4'-FLUOROPHENYL)-1-HYDROXYBUTYL]-3-(HYDROXYMETHYL)-BENZONITRILE HEMI(+)-DI-(p-TOLUOYL) TARTARIC ACID SALT, AND PROCESS FOR PRODUCING (1S)-1-[3-(DIMETHYLAMINO)PROPYL]-1-(4-FLUOROPHENYL)-1,3-DIHYDRO-ISOBENZOFURAN-5-CARBO-NITRILE AND SALT THEREOF USING SAID TARTARIC ACID SALT

PROBLEM TO BE SOLVED: To provide a production process in which (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartaric acid salt that has extremely high chemical purity and optical purity is obtained in high yield. SOLUTION: Provided is a production process characterized in producing a tartaric acid salt as a crystallized product by reacting racemate 4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile with (+)-di-(p-toluoyl) tartaric acid to yield (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartaric acid salt and followed by carrying out crystallization of the tartaric acid salt with a solvent containing 1-butanol. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPO&INPIT

Synthesizing method of escitalopram intermediate and escitalopram intermediate thereof

The invention discloses a synthesizing method of an escitalopram intermediate and escitalopram intermediate thereof. The synthesizing method comprises the following steps of using a compound (2) and acompound (3) as starting raw materials, and performing asymmetric 1,2-addition reaction, so as to obtain an escitalopram intermediate compound (1), wherein a reaction formula is shown in the description. The synthesizing method has the characteristics that the route is novel, the operation is simple and convenient, the synthesizing yield rate is high, the product purity is good, the raw materialsare easy to obtain, the price is low, the synthesizing method is suitable for industrialized production, and the like; the synthesized escitalopram intermediate can provide an intermediate raw material for the preparation of escitalopram.

Asymmetric synthesizing method of escitalopram intermediate and escitalopram intermediate thereof

The invention discloses an asymmetric synthesizing method of an escitalopram intermediate. The asymmetric synthesizing method comprises the following steps of using a compound (2) and a compound (3) as initial raw materials, and performing asymmetric 1,2-addition reaction, so as to obtain an escitalopram intermediate compound (1), wherein a reaction formula is shown in the description. The asymmetric synthesizing method has the characteristics that the route is novel, the operation is simple and convenient, the synthesizing yield rate is high, the product purity is good, the raw materials areeasy to obtain, the price is low, the asymmetric synthesizing method is suitable for industrialized production, and the like; the synthesized escitalopram intermediate can provide an intermediate rawmaterial for the preparation of escitalopram.

NOVEL RECOVERY AND RECYCLING PROCESS OF RACEMIC 4-(4-DIMETHYLAMINO)-1-(4'-FLUOROPHENYL)-1-(HYDROXYBUTYL)-3-(HYDROXYMETHYL)-BENZONITRILE

Disclosed herein is a novel recovery and recycling process of racemic 4-(4- dimethylamino)-1-(4'-fluorophenyl)-1-(hydroxybutyl)-3-(hydroxymethyl)- benzonitrile (hereinafter referred as cyanodiol). The racemic cyanodiol is an intermediate useful for preparation of Citalopram, Escitalopram or pharmaceutically acceptable salts thereof.

Synthesis method of aryl alcohol compound and Escitalopram

The invention discloses a synthesis method of an aryl alcohol compound and Escitalopram. The synthesis method of the aryl alcohol compound comprises the following steps: under gas protection and in an organic solvent and in the presence of transition metal, diphosphine ligand and alkali, the compound of formula 1 reacts with an aryl boron reagent 2. The synthesis method of Escitalopram comprises the following steps: (1) under gas protection and in an organic solvent and in the presence of transition metal, diphosphine ligand and alkali, the compound of formula 4 reacts with the aryl boron reagent 2; (2) under gas protection and in an organic solvent and in the presence of alkali, the compound of formula 5 reacts with dimethylamine or hydrochloride thereof; (3) under gas protection and in an organic solvent and in the presence of organic phosphine ligand and a palladium catalyst, the compound of formula 7 reacts with metal cyanide; and (4) under gas protection and in an organic solvent and in the presence of a reducing agent, the compound of formula 6 reacts. The synthesis method disclosed by the invention has high yield and enantioselectivity.

Structure-activity relationships for a novel series of citalopram (1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5- carbonitrile) analogues at monoamine transporters

(±)-Citalopram (1, 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1, 3-dihydroisobenzofuran-5-carbonitrile), and its eutomer, escitalopram (S-(+)-1) are selective serotonin reuptake inhibitors (SSRIs) that are used clinically to treat anxiety and depression. To further explore structure-activity relationships at the serotonin transporter (SERT), a series of (±)-4- and 5-substituted citalopram analogues were designed, synthesized, and evaluated for binding at the SERT, dopamine transporter (DAT) and norepinephrine transporter (NET) in native rodent tissue. Many of these analogues showed high SERT binding affinities (Ki = 1-40 nM) and selectivities over both NET and DAT. Selected enantiomeric pairs of analogues were synthesized and both retained enantioselectivity as with S- and R-1, wherein S > R at the SERT. In addition, the enantiomeric pairs of 1 and 5 were tested for binding at the homologous bacterial leucine transporter (LeuT), wherein low affinities and the absence of enantioselectivity suggested distinctive binding sites for these compounds at SERT as compared to LeuT. These novel ligands will provide molecular tools to elucidate drug-protein interactions at the SERT and to relate those to behavioral actions in vivo.

PREPARATION OF ESCITALOPRAM, ITS SALTS AND INTERMEDIATES

The present patent application relates to an improved process for the preparation of escitalopram, its salts and intermediates. It also relates to a novel crystalline form S of citalopram diol intermediate, process for preparation and its use in the preparation of citalopram, escitalopram and their salts.