Boehringer Ingelheim International Gmbh

Boehringer Ingelheim Pharma Gmbh & Co Kg

Boehringer Ingelheim Pharma Kg

Joerg Brandenburg

Jutta Kroeber

Ralf Anderskewitz

Werner Rall

Rainer Soyka

Rolf Schmid

Rainer Hamm

Rolf Bauer

Waldemar F Pfrengle

Jun Chi Yan

Nathan K Yee

Xudong Wei

Nizar Haddad

Rogelio Perez Frutos

Fabrice Gallou

Thomas Nicola

Robert Simpson

Juergen Schnaubelt

Ulrich Scholz

Rolf Dach

Dirk Kemmer

Hanfried Baltes

Rolf Herter

Dieter Gutheil

Yibo Xu

Da Deng

Guanghua Lv

Kai Oliver Donsbach

Juncheng Zheng

Robert Hagenkoetter

Michael Schul

Hans-Dieter Ecker

Eric Winter

Waldemar Franz-Augustin Pfrengle

The present invention is directed to an efficient process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form of formula I wherein Rand Rindependently denote C-alkyl groups and Xdenotes an acid anion, such as the chloride, bromide, tosylate, mesylate or trifluoroacetate anion, with high quality, and a process for synthesis of EGFR tyrosine kinase inhibitors with heterocyclic quinazoline, quinoline or pyrimidopyrimidine core structure, using the acid addition salt I and activated derivatives thereof as intermediates.

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The invention relates to a method for producing 1,3-dioxolane-2-ones of general formula (3) in basic reaction conditions by reesterifying the respective ester of general formula (1) in which R1 to R5 have the meanings indicated in the claims and the description. The invention further relates to a method for producing 2-hydroxy carboxylic acid esters of general formula (5) with or without isolation of the intermediate in the form of a derivative of the 1,3-dioxolane-2-one of general formula (3) in basic reaction conditions by reesterifying the respective ester of general formula (1) in which R1, R2, and R6 have the meanings indicated in the claims and the description. The method according to the invention allows the reaction to take place in very gentle basic conditions, causing fewer secondary reactions and providing a greater yield than reactions in highly polar aprotic solvents. Acid-sensitive and/or temperature-sensitive compounds can be synthesized. 

Method for the production of 1,3-dioxolane-2-ones and carboxylic acid esters by means of transacylation in basic reaction conditions

The invention relates to a novel method for producing scopine esters of the general formula (1), wherein X&#x2014;, R, R1, R2, R3, R4, R3', R4&#x2032;, R6 and R6&#x2032; can have the meanings indicated in the claims and in the description. 

Method for producing scopine esters

Disclosed is a process for preparing a macrocyclic compound of the formula (I): which is carried out using an intermediate of the formula (II): wherein W, Rthrough R, D, A and Rare as defined herein. The compounds of formula (I) are potent active agents for the treatment of hepatitis C virus (HCV) infection.

Process for preparing macrocyclic compounds

The invention relates to a process suitable for large-scale industrial use for preparing compounds of general formula (I)wherein:

Process for preparing aryl-iminomethyl-carbamino acid esters

Process for preparing scopine esters

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Wiesbaden, Germany

Joerg Brandenburg