Erregierre S.p.a.

Laboratorio Farmaceutico C.t. S.r.l.

Intercept Pharmaceuticals, Inc.

Stragen Pharma Sa

Massimo Ferrari

Paolo Belotti

Marcello Ghezzi

Daniele De Zani

Matteo Bonaldi

Roberto Cacciaglia

Fabrizio Zinetti

Roberto Pellicciari

Egidio Molinari

Antonio Bonaldi

Stefano Vezzosi

Manuel Alberelli

Alberto Ambrosini

Emanuele Ghezzi

Florindo De Luca

The invention relates to a process for preparation of the compound 3-methyl-5-benzyloxy-2-(4-benzyloxyphenyl)-1H-indole 5, an intermediate for the synthesis of bazedoxifene and bazedoxifene acetate. 

Process for the preparation of bazedoxifene

Crystalline polymorphic forms of a compound of formula N-[4-(trifluoromethyl)benzyl]-4-methoxybutyramide are described. The two polymorphic forms, named polymorphic Form A and polymorphic Form B, can be used in the treatment of drug addiction and alcoholism and have very good stability. Methods for preparing the polymorphic forms are also described.

Polymorphic forms of N-[4-(trifluoromethyl)benzyl]-4-methoxybutyramide

Disclosed is a process for the preparation of toltrazuril of formula (I) via the intermediate N-methyl-N'-[3-methyl-4-[4-[(trifluoromethyl)thio]phenoxy]phenyl] imidodicarbonic diamide of formula (III)  wherein intermediate (III) is obtained via a novel intermediate without the use of potentially hazardous reagents or potentially unstable intermediates.

Process for the preparation of toltrazuril and an intermediate useful for its preparation

The present invention describes a process for the synthesis of ursodeoxycholic acid wherein the purification of the crude ursodeoxycholic acid (containing approximately 13-15% of chenodeoxycholic acid impurity) takes place first passing through a salification with imidazole and a subsequent purification via 'methyl ester', which allows a finished product with an extremely low content of known 'cheno and &#x201c;litho' impurities to be obtained. The present invention also describes the recovery steps of cholic acid and 3&#x3b1;-hydroxy-7-ketocholanic acid from the mother liquors of process intermediates.

Process for preparing high purity ursodeoxycholic acid

The present invention relates, in a first aspect, to a process preparing vilazodone hydrochloride that comprises the reaction of 3-(4-chloro-1-hydroxy-butyl)-1H-indol-5-carbonitrile with 5-piperazin-1-yl-benzofuran-2-carboxylate methyl hydrochloride with the formation of a 1,4-piperazine, with subsequent dehydration, hydrogenation and treatment with ammonia, to obtain vilazodone in free base form that is then converted into the hydrochloride thereof.

Process for preparing vilazodone hydrochloride

There is described a process for the preparation of cinacalcet hydrochloride (I) which includes the steps of: a) reacting (R)-(+)-1-(1-naphthyl)ethylamine (II) with 3-[3-(trifluoromethyl)phenyl]propenaldehyde (III) to afford the non isolated intermediate (R)&#x2014;N-[3-[3-(trifluoromethyl)phenyl]-2-propenylimino-N-[1-(1-naphthyl)ethylamine (IV); b) reducing the non isolated intermediate (R)&#x2014;N-[3-[3-(trifluoromethyl)phenyl]-2-propenylimino-N-[-1-(1-naphthyl)ethylamine (IV) with a sequential addition of:&#x2014;a solution of sodium borohydride, methanol and a base,&#x2014;oxalic acid and&#x2014;a base to obtain (R)&#x2014;N-[3-[3-(tifluoromethyl)phenyl]-2-propenyl]-1-(1-naphthyl)ethylamine (V) by passing through the precipitation of the oxalate salt of compound (V) after the addition of oxalic acid; c) hydrogenating (R)&#x2014;N-[3-[3-(trifluoromethyl)phenyl]-2-propenyl]-1-(1-naphthyl)ethylamine (V) thus obtaining (R)&#x2014;N-(3-(3-(trifluoromethyl)phenyl]propyl]-1-(1-naphthyl)ethylamine cinacalcet base (VI), which is retaken in ethyl acetate; and d) treating the solution of cinacalcet base (VI) in ethyl acetate with hydrochloric acid to afford cinacalcet hydrochloride (I).

Process for the synthesis of cinacalcet hydrochloride

Process for preparing 2-methoxycarbonylmethyl-6,6-dimethyl-2-tetrahydropyran carboxylic acid (I) comprising:

Process for preparing 2-methoxycarbonylmethyl-6,6-dimethyl-2-tetrahydropyran carboxylic acid

Process for preparing 3&#x3b1;-7&#x3b1;(&#x3b2;)-dihydroxy-6&#x3b1;(&#x3b2;)-alkyl-5&#x3b2;-cholanic acid (I) in which R is a linear or branched C-Calkyl and the relative intermediates 3&#x3b1;-hydroxy-6&#x3b2;-alkyl-7-keto-5&#x3b2;-cholanic (VIII) and 3&#x3b1;-hydroxy-6&#x3b1;-alkyl-7-keto-5&#x3b2;-cholanic (IX). 

Process for preparing 3a(&#x3b2;)-7a(&#x3b2;)-dihydroxy-6a(&#x3b2;)-alkyl-5&#x3b2;-cholanic acid

A conversion process of gabapentin hydrochloride into gabapentin comprising: a) dissolution of gabapentin hydrochloride in a solvent in which the gabapentin hydrochloride and the gabapentin are completely soluble; and b) subsequent addition of an amine that allows the removal of the chloride ion from the solution containing gabapentin hydrochloride, by precipitation of the hydrochloride of the same amine, leaving the gabapentin in solution in free amino acid form.

Process for the preparation of 1-(aminomethyl) cyclohexaneacetic acid

Synthetic process of isobutyl methyl 1,4,-dihydro-2,6-dimethyl-4-(2-nitrophenyl)3,5-pyridine dicarboxylate (Nisoldipine) comprising on the reaction of isobutyl 2-(2-nitrobenzylidene)acetoacetate with methyl 3-aminocrotonate in an apolar solvent.

Industrial process for the synthesis of isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylate (nisoldipine)

A process for synthesis of 1-(aminomethyl)cyclohexane acetic acid hydrochloride (Gabapentin hydrochloride) comprising:

Process for synthesis of 1-(aminomethyl)cyclohexane acetic acid hydrochloride

Process for the preparation of ipriflavone consisting in the following steps:

Ipriflavone preparation process

Process for the preparation of derivatives having general formula (I) ##STR1## wherein the meaning of R will be defined in the text, characterized by the reaction between a compound having formula ##STR2## wherein X is an halogen, and an alkaline salt of a methyl dialkylmalonate.

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Massimo Ferrari