Actelion Pharmaceuticals Ltd

Idorsia Pharmaceuticals Ltd

Stefan Abele

Jacques-Alexis Funel

Gunther Schmidt

Ivan Schindelholz

Martin Bolli

Kurt Hilpert

Francis Hubler

Dorte Renneberg

Markus Von Raumer

David Tovell

Daniel To

Lee McLaren

Hans Meier

Heinz Steiner

Stéphanie Combes

Katharina Reichenbaecher

Jean-Philippe Surivet

Stephanie Combes

The present invention relates to a process for the manufacturing of 1-aryl-1-trifluoromethylcyclopropanes, which serve as intermediates for the manufacturing of calcium T channel blockers of the general formula (A) which are described in WO 2015/186056.

Process for the synthesis of 1-aryl-1-trifluoromethylcyclopropanes

The invention relates to a process for manufacturing the compound of formula I wherein R is H, (C-C)alkyl or benzyl, or a salt thereof, said process comprising the reaction of the compound of formula I-1 wherein X is Br, Cl or F, or a salt thereof, with the compound of formula I-2 wherein R is H, (C-C)alkyl or benzyl, or a salt thereof, in the presence of a base, and, when X is Br or Cl, in the presence of tetra-n-butyl ammonium fluoride hydrate or cesium fluoride. The invention further relates to the compound of formula I-1 and uses thereof.

Process for manufacturing pyrimidine sulfamide derivatives

The present invention relates to a new synthetic intermediate, namely the compound of formula I-2 or a salt thereof. Said compound of formula I-2 or its salt can be used to prepare the compound of formula I-3 which is an important synthetic intermediate used in the preparation of macitentan.

Preparation of pyrimidine intermediates useful for the manufacture of macitentan

The invention relates to a process for preparing a pyrimidine intermediate, namely the compound of formula I-2  or a salt thereof, which involves the use of a liquid-liquid extraction using methyl iso-butyl ketone. Said compound of formula I-2 or its salt can be used to prepare macitentan.

Process for preparing a pyrimidine intermediate

The present invention relates to a new process for the preparation of 6-hydroxy-5-arylbicyclo[2.2.2]octan-2-one compounds of the formula (II); which may subsequently be further transformed to compounds of the formula (I):  The present invention further relates to novel compounds as such, which compounds are useful intermediates in the above process.

Preparation of bicyclo[2.2.2]octan-2-one compounds

The invention relates to a new process suitable for manufacturing the compounds of formula I (I) wherein W is H, Br, Cl or methyl, which are synthetic intermediates useful in the preparation of antibiotic compounds.

Process for manufacturing naphthyridine derivatives

The invention relates to a process and synthetic intermediates that can be used for manufacturing the compound of formula (1-6) which is a synthetic intermediate useful in the preparation of antibiotic compounds. 

Process for manufacturing a naphthyridine derivative

The present invention relates to a new process for the preparation of 2-imino-thiazolidin-4-one compounds of the Formula (I) and (II) and to compounds of Formula (II) as such. The present compounds of Formula (II) can be used as intermediates in the preparation of thiazolidin-4-one derivatives of the General Formula (II), said derivatives being described in WO 2005/054215. These compounds of General Formula (II) are described in WO 2005/054215 to act as immunosuppressive agents.

Process for the preparation of 2-imino-thiazolidin-4-one derivatives

The present invention relates to a new process for the diastereoselective preparation of (1R*,4R*,5S*,6S*)-6-hydroxy-5-arylbicyclo[2.2.2]octan-2-one compounds, the compounds of the formula (II), which may subsequently be further transformed to 5-aryl-bicyclo[2.2.2]oct-5-en-2-one compounds of the formula (I):  The present invention further relates to novel (1R*,2S*,3S*,4R*)-6-oxo-3-arylbicyclo[2.2.2]octan-2-yl methanesulfonate compounds as such, which compounds are useful intermediates in the preparation of 5-aryl-bicyclo[2.2.2]oct-5-en-2-one compounds of the formula (I).

Diastereoselective preparation of bicyclo[2.2.2]octan-2-one compounds

The invention relates to crystalline salts of isobutyric acid (1R*,2R*,4R*)-2-(2-{[3-(4,7 -dimethoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl ester, processes for the preparation thereof, pharmaceutical compositions containing said crystalline salts, and their use as medicaments, especially as calcium channel blockers.

Salts of isobutyric acid (1 R*, 2R*, 4R*)-2-(2-{[3-(4,7-dimethoxy-1 H-benzoimidazol-2-yl)-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl ester

The present invention relates to a new process for the preparation of 2-imino-thiazolidin-4-one compounds of the Formula (I) and (II) and to compounds of Formula (II) as such. The present compounds of Formula (II) can be used as intermediates in the preparation of thiazolidin-4-one derivatives of the General Formula (II), which thiazolidin-4-one derivatives being described in WO 2005/054215 to act as immunosuppressive agents.

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Allschwil, Switzerland

Stefan Abele