Crystal forms of immunomodulators

Patent metadata

Field	Value
Publication number	US-11040948-B2
Application number	US-201816651830-A
Country	US
Kind code	B2
Filing date	Sep 27, 2018
Priority date	Sep 29, 2017
Publication date	Jun 22, 2021
Grant date	Jun 22, 2021

Abstract

The invention relates to crystalline forms of a 3-substituted 1,2,4-oxadiazole compound, including an anhydrous crystalline form, methods of their preparation, and related pharmaceutical preparations thereof. The invention also relates to preparations suitable for pharmaceutical, veterinary, and agriculturally-relevant uses.

First claim

The invention claimed is:

1. An anhydrous crystalline compound having the structure of formula (I),

2. The anhydrous crystalline compound of claim 1 , having 2θ values 18.8±0.2, 20.5±0.2, 26.4±0.2, 27.5±0.2, and 32.0±0.2.

3. The anhydrous crystalline compound of claim 2 , having 2θ values 18.8±0.2, 20.5±0.2, 26.1±0.2, 26.4±0.2, 27.5±0.2, 30.6±0.2, and 32.0±0.2.

4. The anhydrous crystalline compound of claim 3 , having 2θ values 15.8±0.2, 16.5±0.2, 18.8±0.2, 20.5±0.2, 25.5±0.2, 26.1±0.2, 26.4±0.2, 27.5±0.2, 30.6±0.2, and 32.0±0.2.

5. The anhydrous crystalline compound of claim 4 , having 2θ values 15.8±0.2, 16.5±0.2, 18.8±0.2, 20.5±0.2, 21.8±0.2, 22.3±0.2, 24.2±0.2, 25.5±0.2, 26.1±0.2, 26.4±0.2, 27.5±0.2, 30.4±0.2, 30.6±0.2, and 32.0±0.2.

6. The anhydrous crystalline compound of claim 5 , having an XRD pattern substantially as shown in FIG. 3 .

7. A pharmaceutical composition comprising the anhydrous crystalline compound of claim 1 and one or more pharmaceutically acceptable excipients.

8. A method for preparing an anhydrous crystalline compound having the structure of formula (I):

comprising the steps of:
a) providing a mixture comprising a compound of formula (I) and a solvent; and
b) crystallizing the compound of formula (I) from the mixture comprising the compound of formula (I).

9. The method of claim 8 , wherein the method comprises the steps of:
a) providing a mixture comprising a compound of formula (I) and a solvent;
b) adding an anti-solvent to the mixture; and
c) crystallizing the compound of formula (I) from the mixture comprising the compound of formula (I).

10. The method of claim 9 , wherein the method comprises the steps of:
a) providing a mixture comprising a compound of formula (I) and a solvent;
b) adding an anti-solvent to the mixture;
c) adding seed crystals to the mixture;
d) adding additional anti-solvent to the mixture; and
e) crystallizing the compound of formula (I) from the mixture comprising the compound of formula (I).

11. The method of claim 8 , wherein the solvent is selected from acetonitrile, anisole, dichloromethane, ethanol, isopropyl acetate, methyl tert-butyl ether (MTBE), n-heptane, tetrahydrofuran, water, and mixtures thereof.

12. The method of claim 11 , wherein the mixture further comprises a solvent selected from ethanol, isopropanol, methanol, tetrahydrofuran, 1,4-dioxane, acetonitrile, and acetone.

13. The method of claim 8 , wherein the mixture comprising the compound of formula (I) and the solvent is a reaction mixture.

14. The method of claim 10 , wherein, the anti-solvent is selected from tetrahydrofuran, methanol, isopropanol, diethyl ether, ethanol, 1,4-dioxane, acetonitrile, and acetone.

15. The method of claim 8 , wherein the mixture further comprises seed crystals.

16. The method of claim 15 , wherein the seed crystals are added at a weight percentage of the total mixture selected from about 1 wt %, about 2 wt %, about 3 wt %, about 4 wt %, about 5 wt %, about 6 wt %, about 7 wt %, about 8 wt %, about 9 wt %, and about 10 wt %.

17. The method of claim 16 , wherein the seed crystals are formula (I) Form A seed crystals.

18. The method of claim 8 , wherein the mixture comprising the compound of formula (I) is a solution.

19. The method of claim 18 , wherein the solution comprises a crude solid material comprising the compound of formula (I) dissolved in a solvent.

20. The method of claim 8 , wherein the mixture comprising the compound of formula (I) is a solution, and the step of crystallizing the compound of formula (I) from the mixture comprises bringing the solution to supersaturation to cause the compound of formula (I) to precipitate out of solution.

21. The method of claim 20 , wherein the step of bringing the solution to supersaturation comprises slowly adding an anti-solvent, allowing the solution to cool, reducing the volume of the solution, or any combination thereof.

22. The method of claim 8 , wherein the mixture comprising the compound of formula (I) is a slurry.

23. The method of claim 22 , wherein the slurry comprises crude solid material comprising the compound of formula (I).

24. The method of claim 19 , wherein the crude solid material comprises about 70% to about 90% compound of formula (I).

25. The method of claim 8 , wherein the purity of the crystalline form of the compound of formula (I) is selected from about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, and about 99%.

Assignees

• Curis Inc

Inventors

• Yu Shu

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D271/06 Primary

  1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles · CPC title

• A61K31/4245

  Oxadiazoles · CPC title