Infosint Sa

Adorkem Technology Spa

Adorken Technology Spa

Clariant Finance (Bvi) Limited

Norpharma S.p.a.

Giovanni Cotticelli

Leone Dall'Asta

Raul Salvetti

Umberto Casazza

Simone Monciardini

Gianluca Di Lernia

Marco Zappa

Silvia Rocchietti

Marco Terreni

Massimo Pregnolato

Giancarlo Ordanini

Giuseppe De Meglio

A new process is described for obtaining 5-cyanophthalide, which is an intermediate used for the synthesis of citalopram and its active enantiomer S(+) citalopram, both of which are known active ingredients commonly used for treating depression. The process involves starting from 5-carboxyphthalide which is converted into the corresponding acylochloride. The latter is reacted with hydroxylamine to produce the corresponding hydroxamyl phthalide, which is subsequently subjected to a dehydration reaction to produce 5-cyanophthalide.

Process for the preparation of 5-cyanophthalide starting from 5-carboxyphthalide

A process is described for the preparation of citalopram (I) and of the active enantiomer thereof, escitalopram (II), which process comprises the cyclisation reaction of the corresponding precursor diol of the formula III or, respectively, IV in the presence of an azodicarboxylate, a phosphine and a strong base.

Process for the preparation of citalopram and escitalopram

A process for preparing an intermediate for synthesizing escitalopram and the pharmaceutically acceptable salts thereof from 4-(4-dimethylamino)-1-(4'-fluorophenyl)-1-(hydroxybutyl)-3-(acyloxymethyl)benzonitrile is described. The process involves converting said intermediate into the (S+) enantiomer of citalopram by means of enzymatic enantiomeric resolution.

Chemo-enzymatic process for the preparation of escitalopram

A process for the preparation of citalopram and the pharmaceutically acceptable salts therof is disclosed by reacting 5-cyanophthalide with a 4-fluorophenyl magnesium halide, reducing the 3-hydroxymethyl-4-(4-fluorobenzoyl)benzonitrile with an agent reducing ketones to alcohols, submitting the thus-obtained 3-hydroxymethyl-4-[(4-fluorophenyl)hydroxymethyl)benzonitrile to a cyclization reaction to give 1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile without 1,1-bis(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile and treating 1,1-bis(4 fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile with a 3-(dimetylamino)propyl halide in the presence of a base.

Process for the preparation of a cyano-isobenzofuran

There is described a process for the preparation of citalopram and of its pharmaceutically acceptable salts, which comprises treating a 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5 isobenzofurancarbaldoxime, O-substituted preferably with a diphenylmethyl or triphenylmethyl group, with formic-acetic anhydride. Furthermore, the total synthesis of citalopram, as free base or in form of its pharmaceutically acceptable salt, starting from 5-formylphthalide is described.

Process for the preparation of 5-substituted isobenzofurans

There is described a process for the preparation of 5-formylphthalide by hydrogenation of a halide of 5-carboxyphthalide, dissolved in a dipolar aprotic solvent, in the presence of a catalyst. Furthermore, the use of 5-formylphthalide in the preparation of citalopram is described.

Process for the preparation of 5-formylphthalide

There is described a process for the preparation of 5-carboxy phthalide, which comprises adding terephthalic acid to fuming sulfuric acid containing at least 20% of SO , then adding formaldehyde to the mixture, heating the mixture at a temperature of 120-145&deg; C. and isolating 5-carboxyphthalide from the reaction mixture.

Process for the preparation of 5-carboxyphthalide

A process for the preparation of 5&prime;-deoxy-5-fluorouridine, which comprises the transformation of 2&prime;,3&prime;-O-isopropylidene-5-fluorouridine in the corresponding 5&prime;-O-sulfonyl derivative, subsequent reaction with alkaline or earth-alkaline iodides and, after hydrolysis of the isopropylidene group, reduction of the 5&prime;-deoxy-5&prime;-iodo-5-fluorouridine thus obtained, is described.

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Cernusco sul Naviglio, Italy

Giovanni Cotticelli