Process for the Preparation of Bosentan
AssigneeDipharma Francis S.R.L.
InventorsMaurizio TADDEI, Diletta Naldini, Pietro Allegrini, Gabriele Razzetti, Simone Mantegazza
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Abstract
A process for the preparation of 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-[2,2′]bipyrimidinyl-4-yl]-benzenesulfonamide, bosentan, comprising the reaction of a compound of formula (II) or a salt thereof, wherein Z is an optionally protected hydroxy group, with a compound of formula (III), in the presence of a base; and, if necessary, the removal of the hydroxy-protecting group, and/or, if desired, the conversion of a compound of formula (I) to a salt thereof, or vice versa; and novel intermediates useful for its synthesis.
Claims15
A process for the preparation of 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-[2,2′]bipyrimidinyl-4-yl]-benzenesulfonamide, of formula (I), or a salt or hydrated form thereof,
- comprising the reaction of a compound of formula (II), or a salt thereof,
- wherein Z is an optionally protected hydroxy group,
- with a compound of formula (III) or a salt thereof,
- in the presence of a base;
- and, if necessary, the removal of the hydroxy-protecting group, and/or, if desired, the conversion of a compound of formula (I) to a salt thereof, or vice versa.
A process according to 1 claim, wherein the base is selected from an alkali metal C1-C6 alkoxide;
- an alkali or alkaline-earth metal hydroxide, carbonate or phosphate.
A process according to 2 claim, wherein the base is an alkali or alkaline-earth metal phosphate.
A compound of formula (II) or a salt thereof,
- wherein Z is an optionally protected hydroxy group.
4-tert-Butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-[2,2′]-bipyrimidinyl-4-yl]-benzenesulfonamide having purity equal to or higher than 99.5%.
4-tert-Butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-[2,2′]-bipyrimidinyl-4-yl]-benzenesulfonamide having mean particle size D50 approximately ranging from 5 to 250 micrometers.
Dependencies are inferred from the claim text.