Ciba-geigy Corporation

Solvias Ag

Speedel Pharma Ag

Umicore Ag & Co Kg

Gruenenthal Gmbh

Novartis Corporation

Novartis Finance Corporation

Novartis Crop Protection, Inc.

Merck + Co., Inc.

Novartis Ag

Lonza Inc.

Syngenta Crop Protection, Inc.

Bayer Pharma Aktiengesellschaft

Actelion Pharmaceuticals Ltd

Grunenthal Gmbh

Felix Spindler

Benoit Pugin

Manfred Muller

Heidi Landert

Benoît Pugin

Andreas Pfaltz

Matthias Lotz

Antonio Togni

Amina Tijani

Peter Herold

Stefan Stutz

Hans-Ulrich Blaser

Ulrich Pittelkow

Björn Gschwend

Nadia Zanetti

Amina Wirth-Tijani

John Anthony Osborn

Walter Weissensteiner

Thomas Sturm

Hermann Rempfler

Wolfgang Hell

Marc Thommen

Hans-Peter Jalett

Markus Kegel

Detlef Heller

Reinhard Georg Hanreich

Willy Urs Lottenbach

Fredrik Cederbaum

Rafael Sablong

Adrian Wyss

Raphael Aardoom

Peter Fey

Pierre Martin

John McGarrity

Oswald K Zimmer

Helmut Buschmann

Britta Olenik

Rudolf Fuchs

Yi Xiao

Wolfgang Skranc

Andreas Hendrikus Maria De Vries

Gerardus Karel Maria Verzijl

Martin Eyer

Kai Lovis

Gerardo Ramos

Nelo R Rivera

Philipp Rubenbauer

Erhard Bappert

Zarghun Nazir

Michael Stanek

Martin Kesselgruber

Joseph D Armstrong, Iii

Yongkui Sun

Thorsten Rosner

Shane W Krska

Julia Küsel

Wilhelm Tschebull

Christoph Imboden

Hans-Joachim Drexler

Olaf Schaefer

Doris Domin

Matthias Helms

Weiping Chen

Urs Siegrist

Frédéric Maurice Naud

You P Chan

Yann Ribourdouille

Xiangdong Feng

Balamurugan Ramalingam

Anita Schnyder

Hans-Joachin Drexler

Markus Müller

Gianpietro Melone

Andrew M Clausen

Christophe Malan

Andreas Hendrikus De Vries

Gerardus Karel Verzijl

Bjoern Gschwend

Olaf SCHÄFER

The present invention relates to a novel and improved process for preparing (3S)-3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclopropylpropanoic acid of the formula (I), to the compound of the formula (I) in crystalline form and to their use for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular, cardiopulmonary and cardiorenal disorders.

Method for producing (3S)-3-(4-chloro-3-{[(2S,3R)-2-(4- chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclo-propylpropanoic acid and the crystalline form thereof for use as a pharmaceutical  ingredient

Compounds of the formula II can be hydrogenated to the corresponding butane derivatives in the presence of homogeneous cataslysts composed of metal salts or complexes containing metals selected from the group consisting of Rh, Ir, and Ru and preferably containing diphosphine ligands, with, in addition, excellent optical yields being achieved when one of Rand Ris not a hydrogen atom and the diphosphine ligand is chiral.

Process for preparing a substituted dimethyl-(3-arylbutyl)amine compound by homogeneous catalysis

Compounds of the formula (I) in the form of a mixture of predominantly one diastereomer or in the form of pure diastereomers,Z-Q-P*RR&#x2003;&#x2003;(I),wherein:

Bidentate chiral ligands for use in catalytic asymmetric addition reactions

Compounds of the formula (I), in the form of mixtures comprising predominantly one diastereomer or in the form of pure diastereomers, Z-Q-P*RR(I) in which Zis a C-bonded, secondary phosphine group &#x2014;P(R); in which R is in each case independently hydrocarbon radicals or heterohydrocarbon radicals, or Zis the &#x2014;P*RRgroup; Q is a bivalent, achiral, aromatic base skeleton, a bivalent, achiral ferrocene base skeleton, an optionally substituted bivalent cycloalkane or heterocycloalkane skeleton, or a C-C-alkylene skeleton.

Compounds of the formula I, in the form of mixtures comprising predominantly one enantiomer or in the form of pure enantiomers, secondary phosphine-Q-P*(&#x2550;O)HR(I) in which secondary phosphine is a C-bonded, secondary phosphine group &#x2014;P(R); in which R is in each case independently hydrocarbon radicals or heterohydrocarbon radicals; Q is a bivalent, achiral, aromatic base skeleton, a bivalent, achiral ferrocene base skeleton, an optionally substituted bivalent cycloalkane or heterocycloalkane skeleton, or a C1-C4-alkylene skeleton, and in which base skeletons a secondary phosphine group is bonded directly to a carbon atom, or, in the case of cyclic base skeletons, directly to a carbon atom or via a C-C-alkylene group, and in which base skeletons a P-chiral group &#x2014;P*(O)HRis bonded to a carbon atom such that the phosphorus atoms are linked via 1 to 7 atoms of a carbon chain optionally interrupted by heteroatoms from the group of O, S, N, Fe or Si; P* is a chiral phosphorus atom; and Ris a hydrocarbon radical, a C-bonded heterohydrocarbon radical or a ferrocenyl radical, with the proviso that Ris an achiral ferrocenyl radical when Q is an achiral ferrocenyl base skeleton. Metal complexes of these ligands in a molar ratio of ligand to metal of about 1.3:1 to 0.9:1 are homogeneous catalysts for asymmetric addition reactions, particularly hydrogenations.

Bidentate secondary phosphine oxide chiral ligands for use in asymmetric addition reactions

The present invention relates to a process for the preparation of the compound of formula (7) which process comprises the hydrogenation of the compound of formula (4) using bis[chloro-1,5-cyclooctadiene-iridium], (S)-i-dicyclohexylphosphino-2-[(S)-&#x3b1;-(dimethylamino)-2-(dicyclohexylphosphino)benzyl]-ferrocene as a catalyst. 

Process for the preparation of an enantiomeric trisubstituted 3,4-dihydro-isoquinoline derivative

Compounds of the formula I in the form of enantiomerically pure diastereomers or a mixture of diastereomers, (I), where the radicals Rare identical or different and are each C-C-alkyl; m is 0 or an integer from 1 to 3; n is 0 or an integer from 1 to 4; Ris a hydrocarbon radical or a C-bonded heterohydrocarbon radical; Cp is unsubstituted or C-C-alkyl-substituted cyclopentadienyl; Y is a C-bonded chiral group which directs metals of metallation reagents into the ortho position; and Phos is a P-bonded P(III) substituent. The compounds are chiral ligands for complexes of transition metals which are used as homogeneous catalysts in asymmetric syntheses. 

Ferrocenediphosphines

Ligands of the formula (I) secondary phosphine-Q-P(&#x2550;O)HR(I) in the form of mixtures of diastereomers or pure diastereomers, in which secondary phosphine is a secondary phosphine group with hydrocarbon radicals or heterohydrocarbon radicals as substituents; Q is a bivalent bisaryl or bisheteroaryl radical with an axial chiral centre to which the two phosphorus atoms are bonded in the ortho positions to the bisaryl or bisheteroaryl bridge bond, or Q is a bivalent ferrocenyl radical with a planar chiral centre or without a planar chiral centre, to which the phosphorus atom of the secondary phosphine is bonded directly or via a C-C-carbon chain to a cyclopentadienyl ring, the &#x2014;P*(&#x2550;O)HRgroup is bonded either on the same cyclopentadienyl ring in ortho position to the bonded secondary phosphine or on the other cyclopentadienyl ring; P* is a chiral phosphorus atom, and Ris a hydrocarbon radical, a heterohydrocarbon radical or a ferrocenyl radical, where Ris a ferrocenyl radical with a planar chiral centre when Q is a ferrocenyl radical without a planar chiral centre. Metal complexes of these ligands are homogeneous catalysts for asymmetric addition reactions, particularly hydrogenations.

Chiral ligands used in transition metal catalysts for asymmetric addition reactions especially hydrogenation

A process for producing 6-dimethylaminomethyl-1-(3-hydroxy- or 3-C-Calkoxyphenyl)-cyclohexane-1,3-diols from 6-dimethylaminomethyl-1-hydroxy-1-(3-hydroxy- or 3-C-Calkoxyphenyl)-cyclohexane-3-ones by catalytic hydrogenation in the presence of heterogeneous or homogeneous catalysts, or by using metal hydrides.

Process for producing 6-dimethylaminomethyl-phenyl-cyclohexane-1,3-diols

Compounds of the formula (I) or (I'), where Ris a hydrogen atom or C-C-alkyl and R&#x2032;is C-C-alkyl; Xand Xare each, independently of one another, a secondary phosphine group; Ris hydrogen, RRRSi&#x2014;, C-C.acyl substituted by halogen, hydroxy, C-C-alkoxy or RRN&#x2014;, -or R&#x2014;X&#x2014;C(O)&#x2014;; R, Rand Rare each, independently of one another, C-C-alkyl, unsubstituted or C-C-alkyl or C-C-alkoxy-substituted C-C-aryl or C-C-aralkyl; Rand Rare each, independently of one another, hydrogen, C-C-alkyl, C-C-cycloalkyl, C-C-aryl or C-C-aralkyl, or Rand Rtogether are trimethylene, tetramethylene, pentamethylene or 3-oxapcntylene; Ris C-C-alkyl, unsubstituted or C-C-alkyl- or C-C-alkoxy-substituted C-C-cycloalkyl, C-C-aryl or C-C-aralkyl; Xis &#x2014;O&#x2014; or &#x2014;NH&#x2014;; T is C-C-arylene; v is 0 or an integer from 1 to 4; and * denotes a mixture of racemic or enantiomerically pure diastereomers or pure racemic or enantiomerically diastereomers, are excellent chiral ligands for metal complexes as enantioselective catalysts for the hydrogenation of prochiral organic compounds. 

Ferrocenyl ligands for homogeneous, enantioselective hydrogenation catalysts

1,1'-Biphenyl-2,2&#x2032;-diphosphines having at least one amine substituent in the para position relative to the phosphine group and having the formulae are ligands for metal complexes which serve as catalysts for asymmetric addition reactions of prochiral organic compounds and whose catalytic properties can be tailored specifically to particular substrates by substitution of the amine group.

Amine-substituted biphenyldiphosphines

The present invention relates to a process for the efficient preparation of enantiomerically enriched beta amino acid derivatives wherein the amino group is unprotected. The product chiral beta amino acid derivatives are useful in the asymmetric synthesis of biologically active molecules. The process comprises an enantioselective hydrogenation of an amine-unprotected prochiral beta-amino acrylic acid or derivative thereof in the presence of a rhodium metal precursor complexed with a chiral mono- or bisphosphine ligand.

Process for the preparation of enantiomerically enriched beta amino acid derivatives

Compounds of the formula (I), in which Ris C-Calkyl, C-Caryi or C-C, aralkyl, Ris an open-chain or cyclic secondary amino group, and R is a radical of the formula in whichis C-Calkyl or C-Calkoxy, and Ris H, C-Calkyl or C-Calkoxy, are ligands for metal complexes as homogeneous hydrogenation catalysts for prochiral organic compounds containing double bonds, by means of which a very high activity and productivity and also enantioselectivity can be achieved 

Substituted ferrocenyldiphosphines as ligands for homogeneous hyrogeneration catalysts

Compounds of formula (I), wherein Rand Rare, independently of one another, H,C-Calkyl, C-Chalogenalkyl, C-Calkoxyl, C-Calkoxy-C-Calkyl, or C-Calkoxy-C-Calkyloxy, and Ris C-Calkyl, are obtainable in high yiedls by stereoselective addition of R-substituted propionic acid esters to R- and R-substituted benzaldehydes of formula R&#x2014;CHO to form corresponding 3-R-3-hydroxy-2-R-propionic acid esters, conversion of the OH group to a leaving group, subsequent regioselective elimination to form 3-R-2-R-propenic acid esters, and reduction to corresponding 3-R-2-R-allyl alcohols and their enantioselective hydrogenation, wherein R is (a).

Process for the preparation of (R)-2-alkyl-3-phenyl-1-propanols

A process for the hydrogenation of imines with hydrogen under elevated pressure in the presence of iridium catalysts and with or without an inert solvent, wherein the reaction mixture contains an ammonium or metal chloride, bromide or iodide and additionally an acid.

Process for the hydrogenation of imines

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Starrkirch-Wil, Switzerland

Felix Spindler