Solid forms of methyl (7aS,2′S)-2-(2-chlorophenyl)-2-(2,4,5,6,7,7a-hexahydrothieno[3,2-c]-5-pyridin-2-one)acetate
New compounds, namely, (7aS,2′S)-2-oxoclopidogrel and its pharmaceutically acceptable salts thereof are disclosed for treatment or prophylaxis of thrombo-embolism and/or cardiovascular diseases.
1. A solid form of substantially pure compound of formula IIA, wherein asterisks denote chiral carbon centers having a (S,S) absolute stereochemical configuration:
and wherein said compound exhibits an X-ray powder diffraction pattern comprising peak reflections in a range starting at 22.22 and ending at 22.8 degrees 2θ; a range starting at 23.0 and ending at 23.6 degrees 2θ; and a range starting at 26.8 and ending at 27.2 degrees 2θ.
2. A solid form of substantially pure compound of formula IIA, wherein the asterisks denote chiral carbon centers having a (S,S) absolute stereochemical configuration,
wherein the compound is isolated substantially free from its other isomers of formulas IIB, VI and VII, wherein the asterisks in Formula IIB denote chiral carbon centers;
and wherein said compound exhibits an X-ray powder diffraction pattern comprising peak reflections in a range starting at 22.22 and ending at 22.8 degrees 2θ; a range starting at 23.0 and ending at 23.6 degrees 2θ; and a range starting at 26.8 and ending at 27.2 degrees 2θ.
3. The compound of claim 2 , wherein the other isomers of Formula IIB, VI or VII are individually or cumulatively less than 10% by weight of the total compound.
4. The compound of claim 2 , wherein the other isomers of Formula IIB, VI and/or VII are less than 3% by weight of the total compound.
5. The compound of claim 2 , wherein the other isomers of Formula IIB, VI and/or VII are less than 1.0% by weight of the total compound.
6. A composition comprising a solid form of substantially pure methyl (7aS,2′S)-2-(2-chlorophenyl)-2-(2,4,5,6,7,7a-hexahydrothieno[3,2-c]-5-pyridin-2-one)acetate that exhibits an X-ray powder diffraction pattern comprising peak reflections in a range starting at 22.22 and ending at 22.8 degrees 2θ; a range starting at 23.0 and ending at 23.6 degrees 2θ; and a range starting at 26.8 and ending at 27.2 degrees 2θ.
7. A solid form of substantially pure bisulfate salt of the compound of formula IIA, wherein the asterisks denote chiral carbon centers having a (S,S) absolute stereochemical configuration:
and wherein said compound exhibits an X-ray powder diffraction pattern comprising peak reflections in a range starting at 7.6 and ending at 8.1 degrees 2θ; a range starting at 21.7 and ending at 22.25 degrees 2θ; and a range starting at 23.75 and ending at 24.2 degrees 2θ.
8. A substantially pure solid bisulfate salt of the compound of formula IIA, wherein the asterisks denote chiral carbon centers having a (S,S) absolute stereochemical configuration,
wherein the compound is isolated substantially free from its other isomers of formulas IIB, VI and VII, wherein the asterisks in Formula IIB denote chiral carbon centers:
and wherein said compound exhibits an X-ray powder diffraction pattern comprising peak reflections in a range starting at 7.6 and ending at 8.1 degrees 2θ; a range starting at 21.7 and ending at 22.25 degrees 2θ; and a range starting at 23.75 and ending at 24.2 degrees 2θ.
9. The compound of claim 8 , wherein the other isomers of Formula IIB, VI or VII are individually or cumulatively less than 10% by weight of the total compound.
10. The compound of claim 8 , wherein the other isomers of Formula IIB, VI and/or VII are less than 3% by weight of the total compound.
11. The compound of claim 8 , wherein the other isomers of Formula IIB, VI and/or VII are less than 1.0% by weight of the total compound.
12. A composition comprising a solid form of substantially pure hydrogen sulfate salt of methyl(7aS,2′S)-2-(2-chlorophenyl)-2-(2,4,5,6,7,7a-hexahydrothieno[3,2-c]-5-pyridin-2-one)acetate that exhibits an X-ray powder diffraction pattern comprising peak reflections in a range starting at 7.6 and ending at 8.1 degrees 2θ; a range starting at 21.7 and ending at 22.25 degrees 2θ; and a range starting at 23.75 and ending at 24.2 degrees 2θ.
13. The solid form of substantially pure methyl (7aS,2′S)-2-(2-chlorophenyl)-2-(2,4,5,6,7,7a-hexahydrothieno[3,2-c]-5-pyridin-2-one)acetate of claim 1 , characterized by having a X-Ray diffraction pattern substantially as shown in FIG. 8 .
14. The solid form of substantially pure hydrogen sulfate salt of methyl (7aS,2′S)-2-(2-chlorophenyl)-2-(2,4,5,6,7,7a-hexahydrothieno[3,2-c]-5-pyridin-2-one)acetate of claim 7 , characterized by having a X-Ray diffraction pattern substantially as shown in FIG. 9 .
15. A pharmaceutical composition comprising a solid compound according to claim 1 , 2 , 7 , or 8 , and pharmaceutically acceptable excipients.
16. A pharmaceutical composition according to claim 15 , wherein the composition further comprises one or more active compounds selected from the group consisting of aspirin, cilostazol, and dipyridamole.