Ciba Specialty Chemicals Corporation

Solvias Ag

Umicore Ag & Co Kg

Polyphor Ag

Marc Thommen

Martin Kesselgruber

Matthias Lotz

Benoît Pugin

Hans-Peter Jalett

Heinz Steiner

Markus Benz

Andreas Hafner

Felix Spindler

Roman Kolly

Hans-J&ouml;rg Kirner

Daniel Obrecht

Pierre Martin

Andreas Pfaltz

Philipp Ermert

Said Oumouch

Frédéric Maurice Naud

Jean-François Gosalbes

Arnaud Piettre

Markus Müller

Gianpietro Melone

Marc Schönleber

Fr&eacute;d&euml;ric Brunner

Fr&eacute;d&eacute;ric Brunner

Jean-Francois Gosalbes

The conformationally restricted, spatially defined macrocyclic ring system of formula (I) is constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. Macrocycles described by this ring system I are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), inhibitory activity on enzymes or antimicrobial activity. In particular, these macrocycles show inhibitory activity on endothelin converting enzyme of subtype 1 (ECE-1) and/or the cysteine protease cathepsin S (CatS), and/or act as antagonists of the oxytocin (OT) receptor, thyrotropin-releasing hormone (TRH) receptor and/or leukotriene B4 (LTB4) receptor, and/or as agonists of the bombesin 3 (BB3) receptor, and/or show antimicrobial activity against at least one bacterial strain. Thus they are showing great potential as medicaments for a variety of diseases. 

Conformationally constrained, fully synthetic macrocyclic compounds

A compound of the formula I or I', where the radicals Rare each, independently of one another, a hydrogen atom or C-C-alkyl and R&#x2032;is C-C-alkyl; Xand Xare each, independently of one another, a sec-phosphino group; Ris (1) hydrogen, (2) RRRSi&#x2014;, (3) C-C-acyl substituted with halogen, hydroxyl, C-C-alkoxy or RRN&#x2014;, or (4) 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-oxapentylene; 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-bonded C-C-heteroarylene; v is 0 or an integer from 1 to 4; Xin the heteroring of the heteroarylene is bound in the ortho position relative to the T&#x2014;C* bond; and * indicates a mixture of racemic or enantiomerically pure diastereomers or pure racemic or enantiomerically pure diastereomers.

Diphosphines and metal complexes

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

Process for preparing a catalyst solution by reacting metal complexes and diphosphines in the presence of an inert organic solvent, which is characterized in that a) an uncharged or cationic metal complex having a TM8 metal as central atom, and b) a salt of a chiral ditertiary diphosphine which has one or two phospholane groups which are bound to a carbon chain having from 2 to 4 carbon atoms and contain anions selected from the group consisting of RCOO, RSO, BF, PF, AsF, SbF, B(CF)and B(3,5-bistrifluoromethylphenyl), are reacted with one another, where the ratio of the components a) and b) is from 1:1 to 1:2 and Ris C-C-haloalkyl, C-C-halocycloalkyl or C-C-haloaryl.

Phospholane salts and their use in enantioselective hydrogenation

The invention relates to compounds having a structural element of formula (I) in an aromatic hydrocarbon ring, wherein: M represents &#x2014;Li, &#x2014;MgX, (C-C-Alkyl)Sn&#x2014;, &#x2014;ZnXor &#x2014;B(O&#x2014;C-C-Alkyl); Xand X, independent of one another, represent O or N, and C-bound hydrocarbon radicals or heterohydrocarbon radicals are bound to the free bonds of the O and N atoms; group &#x2014;C&#x2550;C&#x2014;, together with C atoms, forms a hydrocarbon aromatic compound and represents XCl, Br or I. The inventive compounds are easily obtained by directly substituting the hydrogen in the ortho position to the P atom with metalation reagents. The metal atoms can then be substituted by a reactive electrophilic compound. The group &#x2014;P(X&#x2014;)(X&#x2014;) - - - -(BH)can then be converted into a secondary phosphine group. The inventive method enables the production of monophosphines and diphosphines even on a large scale, which are valuable ligands for metal complexes serving as catalysts for, e.g. enantioselective hydrogenations. 

Method for producing orthometalated and orthosubstituted metallocenes

The invention relates to compounds of formula (I) provided in the form of racemic compounds, mixtures of diastereomers or essentially pure diastereomers, wherein Rrepresents a hydrogen atom or C-C-alkyl, and at least one secondary phosphine depicts an unsubstituted or substituted cyclic phosphine group, or phosphonium salts thereof having one or two monovalent anions or a divalent anion. The compounds of formula (I) can be obtained by means of a novel method and are valuable ligands for catalytically active metal complexes in asymmetrical synthesis 

Ferrocenyl-1,2-diphosphines, the production thereof and their use

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

The invention relates to a process for the cis-selective preparation of cyclic amines of the sertralin type by reductive alkylation of cyclic imines or their precursors and catalytic hydrogenation in the presence of copper-containing catalysts and in the presence of a protic solvent.

Process for the cis-selective catalytic hydrogenation of cyclohexylidenamines

The present invention relates to a process for the preparation of compounds of formula (1), in which R , R and R independently of one another are hydrogen, halogen , trifluoromethyl of or C -C alkoxy, wherein a compound of formula (2), in which R , R and R are as defined in formula (1), is reacted with methlyamine in the presence of a non-alcoholic solvent and, if desired, in the presence of a sulfonic acid catalyst to give the compound of formula (2) and, if desired, is subject to purification by recrystallization.

Process for the preparation of ketimines

Described is a process for the preparation of compounds of formula (1a) which comprises reacting an isomeric mixture consisting of from 75 to 95% of compound of formula (2a) and from 5 to 25% of a compound of formula (2b) with methylamine, in a suitable solvent, to form a sertraline-imine isomeric mixture consisting of from 75 to 95% of formula (1a) and from 5 to 25% of formula (1b)(A ), or reacting an isomeric mixture consisting of from 75 to 95% of a compound of formula (2a) and from 5 to 25% of a compound of formula (2b) with methylamine, in a suitable solvent, using suitable methods of isolation to form an enriched sertraline-imine isomeric mixture, consisting of >99% of a compound of formula (1a) and <1% of a compound of formula (1b)(A ); and then subjecting the sertraline-imine isomeric mixture obtained according to reaction route (A ) or (A ), in a suitable solvent, to recrystallisation (B), in accordance with scheme (I) wherein in formula (1a), R , R and R are each independently of the others hydrogen, halogen, trifluoromethyl or C -C alkoxy and formulae (1b), (2a) and (2b) are as defined in the description.

This invention relates to a process for the cis-selective preparation of cyclic amines of the sertraline type by reductive alkylation of cyclic immines or of their precursors and for the catalytic hydrogenation in the presence of copper-containing catalysts.

Growing community of inventors

Nuglar, Switzerland

Marc Thommen