Unversität Zürich

Janssen Pharmaceutica Nv

Siegfried Ltd.

Azad Pharmaceutical Ingredients Ag

Acino Pharma Ag

Azad Pharmaceuticals Ingredients Ag

University Of Zürich

Thomas Bader

Stefan Horns

Hans-Ulrich Bichsel

Frank Ralf Porstmann

Alfred Stutz

Yoshikazu Suzuki

Sirinporn Thamapipol

Hans Ulrich Bichsel

Changchun Fu

Irène Lehmann

Bruno Gilomen

Imelda Meyer-Wilmes

Harald Hofmeier

Stefan Cilag Ag Horns

Frank Ralf Cilag Ag Porstmann

The present invention relates to the preparation of &#x3b2;-substituted &#x3b3;-amino carboxylic acids, preferably in enantiomerically enriched or even enantiomerically pure form, by a one-pot conversion of a &#x3b2;-substituted &#x3b3;-nitro dicarboxylic acid ester or of a &#x3b2;-substituted &#x3b3;-nitro dicarboxylate of general formula to a &#x3b2;-substituted &#x3b3;-nitro carboxylic acid and a subsequent reduction of the &#x3b3;-nitro group to an amine group. In particular, the present invention relates to the preparation of (S)-pregabalin. In addition, the formation of enantiomerically enriched &#x3b2;-substituted &#x3b3;-amino carboxylic acids and &#x3b2;-substituted &#x3b3;-nitronate carboxylic acid salts are also described.

Method for the preparation of beta-substituted gamma-amino carboxylic acids

The present invention is directed to novel processes for the preparation of paricalcitol to novel intermediates used in these processes, and to processes for preparation of the novel intermediates.

Methods for producing paricalcitol

The present invention relates to a process for isolating (&#x3b1;S,&#x3b2;R)-6-bromo-&#x3b1;-[2-(dimethylamino)ethyl]-2-methoxy-&#x3b1;-1-naphthalenyl-&#x3b2;-phenyl-3-quinolineethanol from a mixture of stereoisomeric forms of 6-bromo-&#x3b1;-[2-(dimethylamino)ethyl]-2-methoxy-&#x3b1;-1-naphthalenyl-&#x3b2;-phenyl-3-quinolineethanol by optical resolution with chiral 4-hydroxydinaphtho[2,1-d:1',2&#x2032;-f][1,3,2]dioxaphosphepin 4-oxide or a derivative thereof, in particular (11bR)-4-hydroxydinaphtho[2,1-d:1&#x2032;,2&#x2032;-f][1,3,2]dioxaphosphepin 4-oxide, as resolution agent.

Process for preparing (alpha S, beta R)-6-bromo-alpha-[2-(dimethylamino)ethyl]-2- methoxy-alpha-1-naphthalenyl-beta-phenyl-3-quinolineethanol

The present invention relates to a process for isolating (&#x3b1;S,&#x3b2;R)-6-bromo-&#x3b1;-[2-(dimethylamino)ethyl]-2-methoxy-&#x3b1;--naphthalenyl-&#x3b2;-phenyl-3-quinolineethanol from a mixture of stereoisomeric forms of 6-bromo-&#x3b1;-[2-(dimethylamino)ethyl]-2-methoxy-&#x3b1;-1-naphthalenyl-&#x3b2;-phenyl-3-quinolineethanol by optical resolution with chiral 4-hydroxydinaphtho[2,1-d:1',2&#x2032;-f][1,3,2]dioxaphosphepin 4-oxide or a derivative thereof, in particular (11bR)-4-hydroxydinaphtho[2,1-d:1&#x2032;,2&#x2032;-f][1,3,2]dioxaphosphepin 4-oxide, as resolution agent.

Process for preparing (alpha S, beta R)-6-bromo-alpha-[2-(dimethylamino) ethyl]-2-methoxy-alpha-1-naphthalenyl-beta-phenyl-3-quinolineethanol

The present invention provides novel polymorphic and pseudopolymorphic forms of Trandolaprilat, including crystalline Trandolaprilat Form A, crystalline Trandolaprilat Form B, crystalline Trandolaprilat Form C, crystalline Trandolaprilat Form D, crystalline Trandolaprilat Form E, and mixtures thereof. The invention also provides novel methods for producing Trandolaprilat, pharmaceutically acceptable salts of Trandolaprilat, and polymorphic and pseudopolymorphic forms of Trandolaprilat, pharmaceutical compositions including one or more novel Trandolaprilat compounds and methods for treating high blood pressure and/or cardiac insufficiency using one or more novel Trandolaprilat compounds.

Polymorphic and pseudopolymorphic forms of trandolaprilat, pharmaceutical compositions and methods for production and use

The present invention provides a novel polymorphic form of olopatadine hydrochloride ([(Z)-3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid hydrochloride), a selective histamine H1-receptor antagonist that is used for the treatment of ocular symptoms of seasonal allergic conjunctivitis. The present invention also provides novel methods for producing olopatadine on a large scale, and in a manner that is cost effective, provides a low level of impurities and eliminates the need to use the costly and dangerous base, butyllithium, which is used in prior art reactions for making olopatadine. The present invention further provides novel processes for carrying out a large scale production of 3-dimethylaminopropyltriphenylphosphonium bromide and its corresponding hydrobromide salt, which are employed in the production of olopatadine, and pharmaceutically acceptable salts of olopatadine.

Polymorphic forms of olopatadine hydrochloride and methods for producing olopatadine and salts thereof

A process of making racemic [2S*[R*[R*[R*]]]] and [2R*[S*[S*[S*]]]]-(&#xb1;)&#x3b1;,&#x3b1;'-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] of the compound of the formula (I) and its pure [2S*[R*[R*[R*]]]]- and [2R*[S*[S*[S*]]]]-enantiomer compounds and pharmaceutically acceptable salts thereof.

Process for preparation of racemic Nebivolol

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Zurich, Switzerland

Thomas Bader