488148-12-5

Upstream product

• 488148-10-3 4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzobromide 
• 123-20-6 vinyl n-butyrate 
• 616217-15-3 C₂₁H₂₅BrFNO₃ 

Downstream Products

• 488148-14-7 (S)-(+)-3-(5-bromo-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine 

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.

METHOD FOR THE SEPARATION OF INTERMEDIATES WHICH MAY BE USED FOR THE PREPARATION OF ESCITALOPRAM

The present invention relates to a novel method for the preparation of diol intermediates having the formula (II) and/or the opposite enantiomer of an acylated diol having the formula (IV) useful for the preparation of escitalopram involving selective enzymatic acylation or deacylation.

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.