Co-crystal compound of rivaroxaban and malonic acid
View Patent ↗The present invention relates to a novel cocrystal compound of 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide (rivaroxaban) and malonic acid, to processes for its preparation, to medicaments comprising this compound and to their use for controlling diseases.
1. A rivaroxaban/malonic acid cocrystal compound of the formula (II)
2. The compound of claim 1 , characterized in that the X-ray diffractogram of the compound has a reflex at a 2-theta angle of 15.8.
3. The compound of claim 1 , characterized in that the Raman spectrum of the compound has a peak at 1617 cm −1 .
4. A process for preparing the compound of claim 1 , comprising dissolving rivaroxaban of the formula (I)
in modification I and malonic acid of the formula (III)
in an inert solvent at a temperature between 50° C. and 90° C. and evaporating the solvent.
5. The process of claim 4 , characterized in that rivaroxaban of the formula (I) in modification I and malonic acid of the formula (III) are employed in a molar ratio of 1:1.
6. The process of claim 4 , characterized in that, prior to evaporation of the solvent, the solution is seeded with crystals of the compound of the formula (II).
7. A process for preparing the compound of claim 1 , comprising suspending rivaroxaban of the formula (I)
in modification I and malonic acid of the formula (III)
in an inert solvent at a temperature between 20° C. and 25° C. and isolating the precipitate formed.
8. A pharmaceutical formulation comprising the compound of claim 1 and an inert nontoxic pharmaceutically suitable auxiliary.
9. A method for the treatment and/or prophylaxis of thromboembolic disorders in humans and animals comprising administering a therapeutically effective amount of the compound of claim 1 to a human or animal in need thereof.
10. A method for prevention of coagulation of blood in vitro comprising adding an anticoagulant amount of the compound of claim 1 to a biological sample that contains factor Xa.
11. A method for the treatment and/or prophylaxis of thromboembolic disorders in humans and animals comprising administering a therapeutically effective amount of the pharmaceutical formulation of claim 8 to a human or animal in need thereof.