488148-10-3

Usage

Uses

1. Used in Pharmaceutical Industry:
1-(4-Bromo-2-(hydroxymethyl)phenyl)-4-(dimethylamino)-1-(4-fluorophenyl)butan-1-olhydrochloride is used as a chemical intermediate for the synthesis of various pharmaceutical compounds. Its unique molecular structure, with multiple functional groups, makes it a versatile building block for the development of new drugs with potential applications in treating various medical conditions.
2. Used in Antidepressant Development:
As an analog of Citadiol, which is a precursor of Citalopram, an antidepressant medication, 1-(4-Bromo-2-(hydroxymethyl)phenyl)-4-(dimethylamino)-1-(4-fluorophenyl)butan-1-olhydrochloride may be used in the development of new antidepressant drugs. Its structural modifications could potentially lead to the discovery of more effective and safer treatments for depression and related mood disorders.
3. Used in Drug Delivery Systems:
Similar to Gallotannin, 1-(4-Bromo-2-(hydroxymethyl)phenyl)-4-(dimethylamino)-1-(4-fluorophenyl)butan-1-olhydrochloride could be explored for its potential in drug delivery systems. Its unique functional groups may allow for the development of novel drug carriers or enhancers that could improve the bioavailability and therapeutic outcomes of various medications.
4. Used in Chemical Research:
Due to its complex structure and functional groups, 1-(4-Bromo-2-(hydroxymethyl)phenyl)-4-(dimethylamino)-1-(4-fluorophenyl)butan-1-olhydrochloride may also be used in chemical research to study various reaction mechanisms, synthetic pathways, and the effects of structural modifications on the properties and reactivity of organic compounds.

Upstream product

• 64169-34-2 5-bromophthalide 
• 64169-64-8 4-bromo-4'-fluoro-2-(hydroxymethyl)benzophenone 
• 19070-16-7 3-(N,N-dimethylamino)propylmagnesium chloride 
• 352-13-6 4-flourophenylmagnesium bromide 

Downstream Products

• 64169-39-7 3-(5-bromo-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine 
• 488148-12-5 (S)-(-)-4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzobromide 
• 616217-14-2 C₂₁H₂₅BrFNO₃ 

Relevant academic research and scientific papers

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.

IMPROVED PROCESS FOR THE MANUFACTURE OF CITALOPRAM HYDROBROMIDE

The present invention describes an improved process for the preparation of extremely pure 1-(4'-Fluorophenyl)-1-(3-dimethylaminopropyl)-5-phthalanecarbonitrile and its bromide salt (citalopram hydrobromide), which is a well known antidepressant. Other aspect of the invention are isolation of crystalline (4-Bromo-2-hydroxymethyl)phenyl-(4-fluorophenyl)-3-(dimethylaminopropyl)methanol (Bromodiol) and conversion of desmethylcitalopram which is formed during the cyanide exchange reaction, to Citalopram by heating with a mixture of formaldhyde and formic acid in chloroform. The resulting citalopram is conventionally purified using extraction methodology.

PROCESSES FOR THE PREPARATION OF ESCITALOPRAM AND ITS PRECURSOR

The present invention relates to an improved process for the preparation of escitalopram of the formula-I which consists of a sequential double Grignard reaction on 5-bromophthalide, isolation of di-magnesium salt, neutralization of di-magnesium salt, resolution of dihydroxy compound of the formula-IV and cyclization of resolved compound of the formula-IV, cyanation of compound of the formula-IV using DMF and copper(I)cyanide. The present process utilizes the insoluble property of di-magnesium salt of formula-XII in a mixture of THF and a non-polar organic solvent and separates it from impurities by simple filtration thereby making the isolation and purification process simple.

PROCESS FOR THE MANUFACTURE OF CITALOPRAM HYDROBROMIDE FROM 5-BROMOPHTHALIDE

A process for the preparation of 1-(4′-fluorophenyl)-1-(3-dimethylamino-propyl)-5-phthalanecarbonitrile of formula (I), or a pharmaceutically acceptable salt thereof, comprising performing two successive Grignard reactions on 5-bromophthalide, wherein the 5-bromophthalide is reacted with the first Grignard reagent in the presence of a Lewis acid, so reducing by-product formation and improving yields.

PROCESS AND INTERMEDIATES FOR PREPARING ESCITALOPRAM

The antidepressant drug Escitalopram is prepared from 5-bromophthalide via the diol intermediate (4-bromo-2-(hydroxymethyl)phenyl)-(4-fluorophenyl)methanol. The racemic diol intermediate is converted to an enantiomerically enriched form by first converting the diol to a monoester intermediate and then reacting the monoester intermediate with an optically active acid, most preferably (+)-di-p-toluoyl tartaric acid, to form a salt. The salt is then crystallized to recover an enantiomerically enriched, crystalline form thereof. The monoester intermediate is preferably formed by reacting the racemic diol intermediate with an acid or a reactive acid derivative which, in a particularly preferred embodiment, is acetic anhydride.