Siegfried Aktiengesellschaft

Acadia Pharmaceuticals Inc.

Wyeth

Galderma S.a.

Other

Contraf-nicotex-tobacco Gmbh

Siegfried (nantong) Pharmaceuticals Co. Ltd.

H. Lundbeck A/s

Indena S.p.a.

Bial-portela Ca & S.a.

Siegried Ag

Beat Theodor Weber

Marlon Carlos

Roger Olsson

Mikael Hillgren

Sagun Tandel

Andreas Philipp Boudier

Stefan Sahli

Matthew J Fleming

Stefan Rosenberger

Ben Pan

Frank Himmelsbach

Matthias Eckhardt

Xiao-Jun Wang

Bing-Shiou Yang

Chutian Shu

Jiang Chen

Monika Brink

Syed Muzafar Shah

Bruno Gabetta

Anthony Francis Hadfield

Daniele Ciceri

Michael William Winkley

Aeri Park

William Maton

Domenico Russo

Karen Sutherland

Brenton William Russell

Rex Alwyn Shipplett

James Andrew Provost

Teofilo Vasconcelos

Lisa Hochstrasser

Ernesto Santandrea

Andreas Boudier

Oliver Geiseler

Nicola Vignola

Patrick Jeger

Frieder Mitzel

Christian Lothschuetz

Bernhard Berger

Rex A Shipplett

Lionel Roux

Jorge Wahnon

Paula Jeronimo

Luisa Sousa

Pedro Barrocas

Christian Lothschütz

Rita Pires

Ricardo Lima

Karen Wiggins Sutherland

Christian LOTHSCHÜTZ

Olma Jacek

Ewa Lukaszewicz

Michal Brysz

Michael SPÄLTI

Paula JERÓNIMO

Teófilo Vasconcelos

Luísa Sousa

Disclosed herein are methods for obtaining N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N-(4-(2-methylpropyloxy)phenylmethyl) carbamide (pimavanserin) comprising the step of contacting an intermediate according to Formula (A) or a salt thereof, with an intermediate Formula B, or a salt thereof, to produce pimavanserin or a salt thereof wherein Y is &#x2014;ORor &#x2014;NRR; Ris hydrogen or substituted or unsubstituted heteroalicyclyl, Ris substituted or unsubstituted aralkyl; X is &#x2014;ORor &#x2014;NRR; (wherein Ris hydrogen or substituted or unsubstituted Calkyl and one of Rand Ris hydrogen and the other is hydrogen or N-methylpiperidin-4-yl); and Ris &#x2014;OCHCH(CH)or F; Also disclosed herein is the tartrate salt of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide and methods for obtaining the salt.

Methods for preparing N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl)carbamide and its tartrate salt and polymorphic form c

Intermediate compounds are described herein and which are used to manufacture a crystalline compound 1-cyano-2-(4-cyclopropyl-benzyl)-4-(&#x3b2;-D-glucopyranos-1-yl)-benzene L-proline monohydrate.

Synthesis of 1:1:1 co-crystal of 1-cyano-2-(4-cyclopropyl-benzyl)-4-(&#xdf;-d-glucopyranos-1-yl)-benzene, L-proline and water

The present invention relates to a method of preparing racemic nicotine comprising: (i) reacting ethyl nicotinate and N-vinylpyrrolidone in the presence of an alcoholate base to 3-nicotinoyl-1-vinylpyrrolidin-2-one; (ii) reacting the 3-nicotinoyl-1-vinylpyrrolidin-2-one with an acid to myosmine; (iii) reducing the myosmine to nornicotine using a reducing agent; and (iv) methylating the nornicotine to obtain the racemic nicotine.

Preparation of racemic nicotine by reaction of ethyl nicotinate with N-vinylpyrrolidone in the presence of an alcoholate base and subsequent process steps

The present invention relates to a method of separating racemic nicotine of Formula (1-a) as a mixture of the (R)- and (S)-enantiomers into the enantiomerically pure (S)- and (R)-nicotine represented by Formula (1-b) and (1-c), by adding a mixture of the L- and the D-enantiomer of a O,O'-disubstituted tartaric acid, wherein the molar ratio of the L- to the D-enantiomer is from 80:20 to 95:5, and obtaining the (S)-nicotine of formula (1-b), or by adding O,O&#x2032;-dibenzoyl-D-tartaric acid and obtaining the (R)-nicotine of formula (1-c). 

Enantiomeric separation of racemic nicotine by addition of an O,O&#x2033;-disubstituted tartaric acid enantiomer

The invention relates to a process for the manufacture of the crystalline compound according to formula (I) comprising the steps (a) deacetylating the final intermediate (FI), (b) forming the crystalline compound according to formula (I) by reacting the deacetylated final intermediate of step (a) with L-proline and water and isolating the final reaction product; processes of manufacturing intermediates thereof; process intermediates and their uses in the processes according to the present invention.

Synthesis of 1:1:1 co-crystal of 1-cyano-2-(4-cyclopropyl-benzyl)-4-(&#x3b2;-D-glucopyranos-1-yl)-benzene, L-proline and water

Disclosed herein are methods for obtaining N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (pimavanserin) comprising the step of contacting an intermediate according to Formula (A) or a salt thereof, with an intermediate Formula B, or a salt thereof, to produce pimavanserin or a salt thereof wherein Y is &#x2014;ORor &#x2014;NRR; Ris hydrogen or substituted or unsubstituted heteroalicyclyl, Ris substituted or unsubstituted aralkyl; X is &#x2014;ORor &#x2014;NRR; (wherein Ris hydrogen or substituted or unsubstituted Calkyl and one of Rand Ris hydrogen and the other is hydrogen or N-methylpiperidin-4-yl); and Ris &#x2014;OCHCH(CH)or F; Also disclosed herein is the tartrate salt of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N&#x2032;-(4-(2-methylpropyloxy)phenylmethyl) carbamide and methods for obtaining the salt. 

Methods for preparing N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl)carbamide and its tartrate salt and polymorphic form

Methods for preparing N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl)carbamide and its tartrate salt and polymorphic form C

The present invention relates to the improved synthesis of noroxymorphone of formula (III). Particularly, the invention shows a way how to reduce the impurity level in the product avoiding lengthy purification steps.

Synthesis of noroxymorphone

The current invention offers a process for the production of N-Boc-2-amino-3,3-dimethylbutyric acid by a reaction of tert-Leucine with di-tert-butyl-dicarbonate, the process comprising (i) contacting the tert-Leucine with di-tert-butyl-dicarbonate in an aqueous medium, optionally comprising a first organic solvent, in the presence of an inorganic base, (ii) optionally removing the first organic solvent, (iii) optionally extracting the resulting N-Boc-2-amino-3,3-dimethylbutyric acid into a second organic solvent, (iv) isolating the product by precipitation from the reaction mixture at acidic pH, and (v) optionally reuse the first and/or second organic solvents recovered from step (ii) and/or step (iv) for the next production cycle. The process is sufficiently short, uses preferably environmental friendly solvents, avoids waste and leads to good yields.

Process for the production of N-Boc-2-amino-3,3-dimethylbutyric acid

The present invention discloses a method of manufacturing 4-chloro-7H-pyrrolo[2,3-d]pyrimidine comprising the steps: a) Preparing ethyl 2-cyano-4,4-dimethoxybutanoate by coupling ethyl 2-cyanoacetate and 2-bromo-1,1-dimethoxyethane; b) Preparing 6-amino-5-(2,2-dimethoxyethyl)pyrimidin-4-ol by adding formamidine to ethyl 2-cyano-4,4-dimethoxybutanoate; c) Converting 6-amino-5-(2,2-dimethoxyethyl)pyrimidin-4-ol to 7H-pyrrolo[2,3-d]pyrimidin-4-ol; and d) Converting the 7H-pyrrolo[2,3-d]pyrimidin-4-ol to 4-chloro-7H-pyrrolo[2,3-d]pyrimidine. The method offers increased yield, less by-products and a decrease in waste compared to methods known as being state of the art.

Method of manufacturing 4-chloro-7H-pyrrolo[2,3-D]pyrimidine

The invention relates to an improved method of preparing buprenorphine, a salt thereof, analogs of buprenorphine and their salts. In particular, the invention relates to a method of preparing buprenorphine and related products and salts in economic and ecologic ways having increased yields.

Method of manufacturing buprenorphine and analogues thereof from oripavine

The present invention provides a compound of formula N wherein: X is CH, oxygen or sulphur; R, Rand Rare the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, alkylcarbonylamino, alkylamino or dialkylamino group, wherein N is in the form of the individual R- and S-enantiomer or a mixture of the (R)- and (S)-enantiomer. The present invention also provides a compound of formula MA. The present invention also provides processes for preparing the above compounds, and processes involving their use. The compounds are particularly useful as intermediates in the synthesis of peripherally-selective inhibitors of dopamine-&#x3b2;-hydroxylase. 

Processes for preparing medicaments for the treatment of cardiovascular diseases and intermediates for use therein

The present invention relates to a method of preparing a compound of Formula II-a' or Formula II-b&#x2032;, wherein Rrepresents hydrogen or a linear, branched and/or cyclic alkyl or alkenyl group having 1 to 10 carbon atoms; Rrepresents a linear, branched and/or cyclic alkyl or alkenyl group having 1 to 10 carbon atoms; Rrepresents hydrogen or a linear, branched and/or cyclic alkyl or alkenyl group having 1 to 10 carbon atoms or a linear, branched and/or cyclic alkoxy group having 1 to 10 carbon atoms; Rrepresents hydrogen or a linear, branched and/or cyclic alkyl group having 1 to 10 carbon atoms or an optionally substituted aryl or alkylaryl group having 6 to 40 carbon atom or acetyl or silyl or a protective group; and Rrepresents hydrogen or a methyl group; wherein Rand Rare different from each other. 

Method of manufacturing stereoisomers of buprenorphine and analogues thereof

The present invention is directed to an improved process to convert morphine into noroxymorphone having economic and ecological advantages.

Synthesis of noroxymorphone from morphine

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Zofingen, Switzerland

Beat Theodor Weber