Rigel Pharmaceuticals, Incorporated

Dsm Fine Chemicals Austria Nfg Gmbh & Co. Kg

Rempex Pharmaceuticals, Inc.

Ulfried Felfer

Michael Wolberg

Karl-Heinz Giselbrecht

Gerhard Steinbauer

Johannes Gerardus De Vries

Peter Poechlauer

Laurent Lefort

Wolfram Hendel

Stefan Steinhofer

Martina Kotthaus

Thomas Heinrich Pabst

Karl Schwendinger

Andreas Pelz

Andreas H M De Vries

Clemens Stueckler

George Winkler

Jeroen Boogers

Bas Ritzen

Michel Goldbach

Marcus Hanacek

Georg Winkler

A process for a continuous production of a boronic acid derivative based on a Matteson boronic ester homologation and an apparatus of performing the process are disclosed.

Apparatus and continuous flow process for production of boronic acid derivatives

Disclosed herein are methods for synthesizing 2,4-pyrimidinediamines as well as intermediates used therein.

Synthesis of 2,4-pyrimidinediamines

A process for transition metal-catalyzed, asymmetric hydrogenation of acrylic acid derivatives of the formula (I) in which R1 is H or an optionally substituted alkyl, aryl or heteroaryl radical, R2 is an optionally substituted alkyl, aryl or heteroaryl radical, and R3 is H or a C-C-alkyl radical, which comprises hydrogenating compounds of the formula (I), optionally in a solvent, in the presence of one or more hydrogen donors, using a catalyst system which comprises a transition metal from the group of ruthenium, rhodium and iridium and a combination of a chiral phosphorus ligand of the formula (II) in which Cn, together with the two oxygen atoms and the phosphorus atom, forms an optionally substituted ring having from 2 to 6 carbon atoms and R4 is an optionally substituted alkyl, aryl, alkoxy or aryloxy radical or NR5R6 where R5 and R6 may each independently be H or an optionally substituted alkyl, aryl, aralkyl or alkaryl radical, or, together with the nitrogen atom, may form a ring, and an achiral phosphine ligand of the formula (III) in which R is an optionally substituted alkyl or aryl radical, to the corresponding compounds of the formula (IV) in which R1, R2 and R3 are each as defined above, and also a novel catalyst system for asymmetric transition metal catalysis.

Process for transition metal-catalyzed asymmetric hydrogenation of acrylic acid derivatives, and a novel catalyst system for asymmetric transition metal catalysis

The invention relates to a method for producing 2-oxindoles from the corresponding isatines of formula (I), wherein R can be H, CH , phenyl or benzyl and R can be H, C -C -alkyl, C -C -alkoxy, phenyl phenoxy, halogen, amino, nitro or hydroxy. Said isatines are converted by means of hydrazine hydrate in a polar solvent at a temperature of 15 to 185&deg; C. to form a corresponding isatine hydrazone which directly undergoes further reaction to form the corresponding 2-oxindole of formula (II) by adding diazabicyclooctane and/or diazabicycloundecane and/or ethyldiisopropylamine as a catalyst in temperatures of 100 to 185&deg; C., whereby the produced reaction water is distilled off. According to formula (II), R and R have the aforementioned definitions. The 2-oxindole is isolated from the reaction mixture by distilling off the solvent and by means of crystallisation.

Method for producing oxindoles

Growing community of inventors

Linz, Austria

Ulfried Felfer