Crystalline form of a β-lactamase inhibitor

1. Hydrate 1 of sodium (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate, wherein Hydrate 1 is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees-2-theta at angles 13.1±0.2°, 14.3±0.2°, 20.5±0.2°, and 21.5±0.2°.

2. The hydrate 1 of claim 1 , wherein the X-ray powder diffraction pattern further comprises a peak expressed in degrees-2-theta at angles 22.2±0.2°.

3. The hydrate 1 of claim 2 , wherein the X-ray powder diffraction pattern further comprises peaks expressed in degrees-2-theta at angles 13.8±0.2°, 26.1±0.2°, 26.9±0.2°, 28.7±0.2°, and 33.5±0.2°.

4. The hydrate 1 of claim 3 , wherein the X-ray powder diffraction pattern comprises peaks expressed in degrees-2-theta at angles 13.1±0.2°, 13.8±0.2°, 20.5±0.2°, 14.3±0.2°, 21.5±0.2°, 22.2±0.2°, 26.1±0.2°, 26.9±0.2°, 33.5±0.2°, and 28.7±0.2°.

5. A pharmaceutical composition comprising the Hydrate 1 of sodium (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate, and a pharmaceutically acceptable carrier, wherein Hydrate 1 is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees-2-theta at angles 13.1±0.2°, 14.3±0.2°, 20.5±0.2°, and 21.5±0.2°.

6. The pharmaceutical composition of claim 5 , wherein the X-ray powder diffraction pattern further comprises a peak expressed in degrees-2-theta at angle 22.2±0.2°.

7. The pharmaceutical composition of claim 6 , wherein the X-ray powder diffraction pattern further comprises peaks expressed in degrees-2-theta at angles 13.8±0.2°, 26.1±0.2°, 26.9±0.2°, 28.7±0.2°, and 33.5±0.2°.

8. A pharmaceutical composition comprising the Hydrate 1 of claim 1 and at least one β-lactam antibiotic, wherein Hydrate 1 is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees-2-theta at angles 13.1±0.2°, 14.3±0.2°, 20.5±0.2°, and 21.5±0.2°.

9. The pharmaceutical composition of claim 8 , wherein the X-ray powder diffraction pattern further comprises a peak expressed in degrees-2-theta at angle 22.2±0.2°.

10. The pharmaceutical composition of claim 9 , wherein the X-ray powder diffraction pattern further comprises peaks expressed in degrees-2-theta at angles 13.8±0.2°, 26.1±0.2°, 26.9±0.2°, 28.7±0.2°, and 33.5±0.2°.

11. A method of treating a bacterial infection comprising administering to a subject in need thereof a therapeutically-effective amount of the compound of claim 1 .

12. The method of claim 11 , wherein the X-ray powder diffraction pattern further comprises a peak expressed in degrees-2-theta at angle 22.2±0.2°.

13. The method of claim 12 , wherein the X-ray powder diffraction pattern further comprises peaks expressed in degrees-2-theta at angles 13.8±0.2°, 26.1±0.2°, 26.9±0.2°, 28.7±0.2°, and 33.5±0.2°.

14. A method of treating a bacterial infection comprising administering to a subject in need thereof a therapeutically-effective amount of the pharmaceutical composition of claim 5 .

15. A method of treating a bacterial infection comprising administering to a subject in need thereof a therapeutically-effective amount of the pharmaceutical composition of claim 8 .

16. A method of making the compound of claim 1 comprising:

(a) combining sodium (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate and a solvent, such that a solution of sodium (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate is formed; and

(b) combining an antisolvent with the solution, wherein the antisolvent is miscible with the solvent and wherein sodium (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate is partially or completely insoluble in the antisolvent, such that crystalline Hydrate 1 precipitates from the solution.

17. The method of claim 16 , wherein the antisolvent in step (b) of the method is THF or acetonitrile.

18. A pharmaceutical composition comprising (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate obtained from a solution formed by dissolving a solid form of (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate characterized by an X-ray powder diffraction pattern having peaks expressed in degrees-2-theta at angles 13.1±0.2°, 14.3±0.2°, 20.5±0.2°, and 21.5±0.2°.

19. The pharmaceutical composition of claim 18 , obtained by a process comprising the steps of:

(a) forming a solution of a solid form of (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate characterized by an X-ray powder diffraction pattern having peaks expressed in degrees-2-theta at angles 13.1±0.2°, 14.3±0.2°, 20.5±0.2°, and 21.5±0.2°; and

(b) obtaining the (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate in the pharmaceutical composition from the solution in step (a).

20. The pharmaceutical composition of claim 18 , obtained by a process comprising the steps of:

(a) dissolving a solid form of (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate characterized by an X-ray powder diffraction pattern having peaks expressed in degrees-2-theta at angles 13.1±0.2°, 14.3±0.2°, 20.5±0.2°, and 21.5±0.2° in an aqueous solution; and

(b) lyophilizing the aqueous solution of step (a) to obtain the (2S,5R)-2-(1,3,4-oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate in the pharmaceutical composition.