(N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide
The present invention relates to stable novel salt forms of N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide that are suitable for the preparation of pharmaceutical formulations thereof, and their therapeutic use.
1. A method of treating myelofibrosis or polycythemia vera comprising administering to a subject in need thereof a compound selected from the group consisting of:
N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II;
N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form I; and
N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form III.
2. The method of claim 1 , wherein the compound is in a crystalline form.
3. The method of claim 2 , wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II.
4. The method of claim 3 , wherein the crystals have unit cell parameters at T=100° K of: a=10.2837(6) Å, b=10.4981(6) Å, c=11.5143(7) Å, α=83.297(2)°, β=87.649(2)°, γ=67.445(2)°, and a triclinic P-1 space group.
5. The method of claim 3 , wherein the crystalline form is characterized by an x-ray powder diffraction (XRPD) pattern substantially as set forth in FIG. 5 .
6. The method of claim 3 , wherein the crystalline form is characterized by an x-ray powder diffraction (XRPD) pattern having peaks at about 7.7°, 19.3°, 24.0°, 25.7°, and 29.6° 2-θ±0.2° 2-θ.
7. The method of claim 3 , wherein the crystalline form is characterized by differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 8 .
8. The method of claim 3 , wherein the crystalline form is characterized by a dynamic vapor sorption (DVS) pattern substantially as set forth in FIG. 14 .
9. The method of claim 2 , wherein the crystalline form is crystalline N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form I.
10. The method of claim 9 , wherein the crystalline form is characterized by an x-ray powder diffraction (XRPD) pattern substantially as set forth in FIG. 6 .
11. The method of claim 9 , wherein the crystalline form is characterized by an X-ray powder diffraction (XRPD) pattern having peaks at about 13.5°, 20.9°, 26.1°, 26.6°, and 28.3° 2-θ±0.2° 2-θ.
12. The method of claim 9 , wherein the crystalline form is characterized by a differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 9 .
13. The method of claim 2 , wherein the crystalline form is crystalline N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form III.
14. The method of claim 13 , wherein the crystalline form is characterized by an x-ray powder diffraction (XRPD) pattern substantially as set forth in FIG. 7 .
15. The method of claim 13 , wherein the crystalline form is characterized by an X-ray powder diffraction (XRPD) pattern having peaks at about 12.7°, 14.6°, 17.8°, 19.7°, and 23.3° 2-θ±0.2° 2-θ.
16. The method of claim 13 , wherein the crystalline form is characterized by a differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 10 .