Zach System

Teva Pharmaceutical Industries Limited

Novacta Biosystem Limited

Novacta Biosystems Limited

Alain Burgos

Yvon Derrien

Sylvie Blanchet

Sonia Roussiasse

Blandine Bertrand

Jean-François Pluvie

Juliette Martin

Florence Perrin

Jean-Claude Caille

Patricia Poirier

Valéry Dambrin

Michelle Lorraine-Gradley

Eric Chenard

Françoise Bourdeau

Stëphane Frein

Jacques Tonnel

Denis Lucet

Stéphane Frein

Bertrand Blandine

Marie-Laure Moreau

The present invention relates to a process for the preparation of nebivolol and, more particularly, to an improved process of synthesizing an alpha-haloketone of formula a key intermediate in the preparation of nebivolol.

Method for preparing nebivolol

This disclosure relates to the synthesis of the compound of formula (I) according to Scheme A below: in which R1, R2 and R3, which may be identical or different, represent, individually and independently, an alkyl group, characterized by an enzymatic hydrolysis reaction that involves placing the compound of formula (II) in contact with an enzyme that performs a chemoselective hydrolysis of only one of the two ester functions of the compound of formula (II) to obtain the compound of formula (I).

Method for the chemo-selective enzymatic hydrolysis if a diester compound for preparing a monoester monoacid compound

A process for the production of ene-amide derivatives represented by the formula (I) wherein R1 and R2 and R3 are independently a hydrogen atom, an alkyl, a cycloalkyl, a cycloalkylalkyl, an alkylaryl, an aryl, a heterocycle, a cyano, an alkoxy, an aryloxy, a carboxyl, a carbamoyl, &#x2014;CONR5R6 (in which R5 and R6 are independently an alkyl, arylalkyl or aryl group said ring being substituted or not with a functional group or with R5) or &#x2014;COOR5 group (in which R5 is an alkyl, alkylaryl or aryl group), said alkyl, cycloalkyl, cycloalkylalkyl, alkylaryl and aryl groups being substituted or not with a functional group or with R5; or R1 and R2 taken together, may form a ring (which terms includes mono-, di- and higher polycyclic ring systems); R4 is a hydrogen atom, an alkyl, an aryl, an alkylaryl, said groups are substituted or not with a halogen atom as Cl, Br, or F; X is an oxygen atom or a leaving group and m is an integer 1 or 2; when m is 1 then X is a leaving group; when m is 2 then X is a oxygen atom, which comprise: a hydrogenation/isomerization reaction in presence of a heterogeneous catalyst, of an oxime derivatives of formula (II) wherein R1, R2 and R3 are as defined above with an acyl derivative of formula (III) (R4CO)X wherein R4, m and X are as defined above.

Process for the synthesis of eneamide derivatives

A process is used for the preparation of 1,3,2-oxazaborolidine compounds. This process prepares compounds of formula (I) or (IA): in which: This process avoids by-products and exhibits a very good stereospecificity.

Process for the preparation of 1,3,2-oxazaborolidine compounds

An in situ or one-pot process for the preparation of the compounds of formula (I) uses a compound of general formula (I):  and includes: a) the hydrogenation of a nitrile group of the compound of general formula (II):  in which Rto R4 are especially H or alkyl and n varies from 0 to 4, in the presence of a hydrogenation catalyst, a methylating agent and an organic acid as solvent, and at a temperature Ta below the initiation temperature of a reductive amination reaction, to give a primary amine from the nitrile group; and b) the reductive amination of the primary amine in the presence of hydrogen, at a temperature Tb above Ta, to give the dimethylated amine of general formula (I) by activation of the methylating age.

In situ or one-pot hydrogenation and reductive amination process

A process for the preparation of optically active substituted alpha-amino-indane derivatives of formula (I), which include: an asymmetric hydrogenation reaction of an en-amide derivative of formula (III) in presence of hydrogen and an optically active catalyst, in order to obtain an amide derivative of formula (II), a hydrolysis reaction of the amide derivative of formula (II) obtained in the previous step, in order to obtain optically active substituted alpha-amino-indane derivatives of formula (I).

Process for the synthesis of substituted alpha-aminoindan derivatives

A process for the in situ preparation of chiral compounds derived from oxazaborolidine-borane complexes, wherein a metal borohydride, a Lewis base and an inorganic acid ester are brought together and an optically active amino alcohol and optionally a halide are then added. The compound obtained is a complex that is useful as a catalyst in asymmetric reduction reactions. The reaction is performed by adding the substance to be reduced, particularly prochiral ketones or ether oximes, in order to synthesize chiral alcohols or chiral amines.

Method for the in situ preparation of chiral compounds derived from oxazaborolidine-borane complexes which are used in asymmetric reduction reactions

A process for preparing indanylamine and aminotetralin derivatives from indanone or tetralone oximes by acylating the oximes with an organic anhydride, followed by catalytic hydrogenation in the presence of an organic anhydride with subsequent hydrolysis is described. The process is commercially feasible providing indanylamine and aminotetralin derivatives in high yield that are useful as intermediates in the production of therapeutically active compounds. Also described are novel intermediates, 1-indanone O-acetyl oximes and 1-tetralone O-acetyl oximes.

Process for the synthesis of indanylamine or aminotetralin derivatives and novel intermediates

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Les Ponts de Ce, France

Alain Burgos