Actelion Pharmaceuticals Ltd

Idorsia Pharmaceuticals Ltd

Ivan Schindelholz

Martin Bolli

Martine Clozel

Stefan Abele

Jacques-Alexis Funel

Markus Von Raumer

Marc Bellet

Marc Iglarz

Philipp Kohler

The present invention concerns novel crystalline forms of {5-(4-bromo-phenyl)-6 [2 (5 bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl}-sulfamide, processes for the preparation thereof, pharmaceutical compositions comprising said crystalline forms, pharmaceutical compositions prepared from such crystalline forms, and their use as endothelin receptor antagonists. It also relates to new uses of {5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl}-sulfamide, either alone or in combination with other active ingredients or therapeutic agents.

Crystalline forms of a 4-pyrimidinesulfamide derivative aprocitentan

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.

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Allschwil, Switzerland

Ivan Schindelholz