Claims for Patent: 9,447,071

Summary for Patent: 9,447,071

Title:	Crystalline polymorphs of the free base of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzald- ehyde
Abstract:	Disclosed are crystalline free base ansolvate forms of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzald- ehyde (or Compound 1), such as the free base Form I, Form II and Material N. Also disclosed are crystalline free base solvates of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzald- ehyde (or Compound 1).
Inventor(s):	Li; Zhe (South San Francisco, CA), Parent; Stephan D. (South San Francisco, CA), Houston; Travis (South San Francisco, CA)
Assignee:	Global Blood Therapeutics, Inc. (South San Francisco, CA)
Application Number:	14/616,548
Patent Claims:	1. A crystalline ansolvate of Compound 1: ##STR00011## wherein the crystalline ansolvate is characterized by at least one X-ray powder diffraction peak (Cu K.alpha. radiation) selected from 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 2. The crystalline ansolvate of claim 1, characterized by at least two X-ray powder diffraction peaks (Cu K.alpha. radiation) selected from 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 3. The crystalline ansolvate of claim 1, characterized by at least three X-ray powder diffraction peaks (Cu K.alpha. radiation) selected from 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 4. The crystalline ansolvate of claim 1, characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 5. The crystalline ansolvate of Compound 1 of claim 1, wherein the crystalline ansolvate is characterized by an X-ray powder diffraction pattern (Cu K.alpha. radiation) substantially similar to that of FIG. 5. 6. A composition comprising a crystalline ansolvate of Compound 1: ##STR00012## wherein the crystalline ansolvate of Compound 1 is characterized by at least one X-ray powder diffraction peak (Cu K.alpha. radiation) selected from 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 7. The composition of claim 6, wherein the crystalline ansolvate of Compound 1 is characterized by at least two X-ray powder diffraction peaks (Cu K.alpha. radiation) selected from 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 8. The composition of claim 6, wherein the crystalline ansolvate of Compound 1 is characterized by at least three X-ray powder diffraction peaks (Cu K.alpha. radiation) selected from 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 9. The composition of claim 6, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 10. The composition of claim 6, wherein the crystalline ansolvate is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 25 mole % of crystalline Form I. 11. The composition of claim 10, wherein the crystalline ansolvate of Compound 1 is substantially free of a solvated polymorph of Compound 1. 12. A pharmaceutical composition comprising a crystalline ansolvate of Compound 1: ##STR00013## and at least one pharmaceutically acceptable excipient wherein the crystalline ansolvate of Compound 1 is characterized by at least one X-ray powder diffraction peak (Cu K.alpha. radiation) selected from 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 13. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by at least two X-ray powder diffraction peaks (Cu K.alpha. radiation) selected from 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 14. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by at least three X-ray powder diffraction peaks (Cu K.alpha. radiation) selected from 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 15. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.). 16. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 25 mole % of crystalline Form I. 17. The pharmaceutical composition of claim 16, wherein the crystalline ansolvate of Compound 1 is substantially free of a solvated polymorph of Compound 1. 18. The composition of claim 6, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 25 mole % of crystalline Material N. 19. The composition of claim 6, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 25 mole % of amorphous forms of Compound 1. 20. The composition of claim 6, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 10 mole % of crystalline Form I. 21. The composition of claim 6, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 10 mole % of crystalline Material N. 22. The composition of claim 6, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 10 mole % of amorphous forms of Compound 1. 23. The composition of claim 6, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 5 mole % of crystalline Form I. 24. The composition of claim 6, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 5 mole % of crystalline Material N. 25. The composition of claim 6, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 5 mole % of amorphous forms of Compound 1. 26. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 25 mole % of crystalline Material N. 27. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 25 mole % of amorphous forms of Compound 1. 28. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 10 mole % of crystalline Form I. 29. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 10 mole % of crystalline Material N. 30. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 10 mole % of amorphous forms of Compound 1. 31. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 5 mole % of crystalline Form I. 32. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 5 mole % of crystalline Material N. 33. The pharmaceutical composition of claim 12, wherein the crystalline ansolvate of Compound 1 is characterized by X-ray powder diffraction peaks (Cu K.alpha. radiation) of 13.37.degree., 14.37.degree., 19.95.degree. and 23.92.degree. 2.theta. (each .+-.0.2.degree. 2.theta.), and less than 5 mole % of amorphous forms of Compound 1.