Crystalline forms of 3-substituted 1,2,4-oxadiazole
The invention relates to crystalline forms of a 3-substituted 1,2,4-oxadiazole compound, methods of their preparation, and related pharmaceutical preparations thereof. The invention also relates to preparations suitable for pharmaceutical, veterinary, and agriculturally-relevant uses.
1. A method for preparing a crystalline compound having the structure of formula
comprising:
a) providing a mixture comprising a compound of formula (I) and a solvent;
b) crystallizing the compound of formula (I) from the mixture comprising the compound of formula (I); and
wherein, prior to step a), the compound of formula (I) is in a solution and step a) comprises contacting the solution with vapor of the solvent, thereby forming the mixture of step a).
2. The method of claim 1 , wherein the solution is prepared by filtering a suspension comprising compound of formula (I), thereby forming the solution.
3. The method of claim 1 , wherein the solvent is selected from acetonitrile, anisole, dichloromethane, ethanol, isopropyl acetate, methyl tert-butyl ether (MTBE), n-heptane, tetrahydrofuran, water, and mixtures thereof.
4. The method of claim 1 , wherein the purity of the crystalline compound is selected from about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, and about 99%.
5. The crystalline compound of claim 1 , wherein the crystalline compound is a solvate.
6. The method of claim 1 , wherein the crystalline compound is a hydrate.
7. The method of claim 1 , wherein the crystalline compound is a monohydrate.
8. The method of claim 1 , wherein the crystalline compound has 2θ values 8.4±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 21.4±0.2, and 28.4±0.2.
9. The method of claim 1 , wherein the crystalline compound has 2θ values 8.4±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 19.3±0.2, 20.4±0.2, 21.4±0.2, and 28.4±0.2.
10. The method of claim 1 , wherein the crystalline compound has 2θ values 8.4±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 19.3±0.2, 19.9±0.2, 20.4±0.2, 21.4±0.2, 24.5±0.2, 26.5±0.2, and 28.4±0.2.
11. The method of claim 1 , wherein the crystalline compound has 2θ values 8.4±0.2, 11.5±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 19.3±0.2, 19.9±0.2, 20.4±0.2, 21.4±0.2, 21.8±0.2, 24.5±0.2, 26.5±0.2, 27.5±0.2, 28.0±0.2, 28.4±0.2, 30.0±0.2, and 32.4±0.2.
12. The method of claim 1 , wherein the crystalline compound has an XRD pattern substantially as shown in FIG. 1 .
13. The method of claim 1 , wherein the crystalline compound has 2θ values of 6.8±0.2, 8.4±0.2, 10.0±0.2, 10.6±0.2, 11.5±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 17.6±0.2, 18.8±0.2, 19.3±0.2, 19.9±0.2, 20.4±0.2, 20.6±0.2, 21.00±0.2, 21.4±0.2, 21.8±0.2, 22.6±0.2, 23.6±0.2, 24.5±0.2, 24.8±0.2, 25.3±0.2, 26.5±0.2, 27.1±0.2, 27.5±0.2, 28.0±0.2, 28.4±0.2, 29.3±0.2, 30.1±0.2, 30.8±0.2, 31.5±0.2, 32.4±0.2, 33.0±0.2, 33.5±0.2, 34.3±0.2, 35.3±0.2, 36.5±0.2, 37.6±0.2, 38.1±0.2, and 38.7±0.2.
14. The method of claim 1 , wherein the crystalline compound has 2θ values of 10.9±0.2, 11.6±0.2, 12.9±0.2, 13.5±0.2, 15.7±0.2, 16.1±0.2, 17.0±0.2, 19.6±0.2, 19.6±0.2, 20.3±0.2, 21.1±0.2, 21.4±0.2, 22.2±0.2, 22.9±0.2, 24.2±0.2, 24.5±0.2, 24.8±0.2, 25.1±0.2, 25.8±0.2, 26.2±0.2, 26.4±0.2, 27.2±0.2, 28.2±0.2, 28.9±0.2, 29.7±0.2, 30.2±0.2, 31.0±0.2, 32.2±0.2, 33.7±0.2, 34.2±0.2, 36.0±0.2, 37.0±0.2, 38.4±0.2, and 39.0±0.2.
15. A method for preparing a crystalline compound having the structure of formula (I):
comprising exposing a solid form of the compound of formula (I) to vapor of a solvent, thereby obtaining the crystalline compound.
16. The method of claim 15 , wherein the solvent is selected from acetonitrile, anisole, dichloromethane, ethanol, isopropyl acetate, methyl tert-butyl ether (MTBE), n-heptane, tetrahydrofuran, water, and mixtures thereof.
17. The method of claim 15 , wherein the purity of the crystalline compound is selected from about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, and about 99%.
18. The method of claim 15 , wherein the compound is solvated.
19. The method of claim 15 , wherein the crystalline compound is a hydrate.
20. The method of claim 15 , wherein the crystalline compound is a monohydrate.
21. The method of claim 15 , wherein the crystalline compound has 2θ values 8.4±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 21.4±0.2, and 28.4±0.2.
22. The method of claim 15 , wherein the crystalline compound has 2θ values 8.4±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 19.3±0.2, 20.4±0.2, 21.4±0.2, and 28.4±0.2.
23. The method of claim 15 , wherein the crystalline compound has 2θ values 8.4±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 19.3±0.2, 19.9±0.2, 20.4±0.2, 21.4±0.2, 24.5±0.2, 26.5±0.2, and 28.4±0.2.
24. The method of claim 15 , wherein the crystalline compound has 2θ values of 8.4±0.2, 11.5±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 19.3±0.2, 19.9±0.2, 20.4±0.2, 21.4±0.2, 21.8±0.2, 24.5±0.2, 26.5±0.2, 27.5±0.2, 28.0±0.2, 28.4±0.2, 30.0±0.2, and 32.4±0.2.
25. The method of claim 15 , wherein the crystalline compound has an XRD pattern substantially as shown in FIG. 1 .
26. The method of claim 15 , wherein the crystalline compound has 2θ values of 6.8±0.2, 8.4±0.2, 10.0±0.2, 10.6±0.2, 11.5±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 17.6±0.2, 18.8±0.2, 19.3±0.2, 19.9±0.2, 20.4±0.2, 20.6±0.2, 21.00±0.2, 21.4±0.2, 21.8±0.2, 22.6±0.2, 23.6±0.2, 24.5±0.2, 24.8±0.2, 25.3±0.2, 26.5±0.2, 27.1±0.2, 27.5±0.2, 28.0±0.2, 28.4±0.2, 29.3±0.2, 30.1±0.2, 30.8±0.2, 31.5±0.2, 32.4±0.2, 33.0±0.2, 33.5±0.2, 34.3±0.2, 35.3±0.2, 36.5±0.2, 37.6±0.2, 38.1±0.2, and 38.7±0.2.
27. The method of claim 15 , wherein the crystalline compound has 2θ values of 10.9±0.2, 11.6±0.2, 12.9±0.2, 13.5±0.2, 15.7±0.2, 16.1±0.2, 17.0±0.2, 19.1±0.2, 19.6±0.2, 20.3±0.2, 21.1±0.2, 21.4±0.2, 22.2±0.2, 22.9±0.2, 24.2±0.2, 24.5±0.2, 24.8±0.2, 25.1±0.2, 25.8±0.2, 26.2±0.2, 26.4±0.2, 27.2±0.2, 28.2±0.2, 28.9±0.2, 29.7±0.2, 30.2±0.2, 31.0±0.2, 32.2±0.2, 33.7±0.2, 34.2±0.2, 36.0±0.2, 37.0±0.2, 38.4±0.2, and 39.0±0.2.
28. A crystalline compound having the structure of formula (I):
and 2θ values of 6.8±0.2, 8.4±0.2, 10.0±0.2, 10.6±0.2, 11.5±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 17.6±0.2, 18.8±0.2, 19.3±0.2, 19.9±0.2, 20.4±0.2, 20.6±0.2, 21.00±0.2, 21.4±0.2, 21.8±0.2, 22.6±0.2, 23.6±0.2, 24.5±0.2, 24.8±0.2, 25.3±0.2, 26.5±0.2, 27.1±0.2, 27.5±0.2, 28.0±0.2, 28.4±0.2, 29.3±0.2, 30.1±0.2, 30.8±0.2, 31.5±0.2, 32.4±0.2, 33.0±0.2, 33.5±0.2, 34.3±0.2, 35.3±0.2, 36.5±0.2, 37.6±0.2, 38.1±0.2, and 38.7±0.2.
29. The crystalline compound of claim 28 , wherein the purity of the crystalline compound is selected from about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, and about 99%.
30. A crystalline compound having the structure of formula (I):
and 2θ values of 10.9±0.2, 11.6±0.2, 12.9±0.2, 13.5±0.2, 15.7±0.2, 16.1±0.2, 17.0±0.2, 19.1±0.2, 19.6±0.2, 20.3±0.2, 21.1±0.2, 21.4±0.2, 22.2±0.2, 22.9±0.2, 24.2±0.2, 24.5±0.2, 24.8±0.2, 25.1±0.2, 25.8±0.2, 26.2±0.2, 26.4±0.2, 27.2±0.2, 28.2±0.2, 28.9±0.2, 29.7±0.2, 30.2±0.2, 31.0±0.2, 32.2±0.2, 33.7±0.2, 34.2±0.2, 36.0±0.2, 37.0±0.2, 38.4±0.2, and 39.0±0.2.
31. The crystalline compound of claim 30 , wherein the purity of the crystalline compound is selected from about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, and about 99%.