N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide

1. A compound selected from the group consisting of:

N-(cyanomethyl)-4-(2-(4-morpholinoohenylamino)pyrimidin-4-yl)benzamide N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II;

N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrirnidin-4-yl)benzarnide 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 compound of claim 1 in a crystalline form.

3. The crystalline form of claim 2 , wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylarnino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II.

4. The crystalline form of claim 3 2, wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II and 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 β=87.649(2)°, y=67.445(2)°, and a triclinic P-1 space group.

5. The crystalline form of claim 3 2, wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II and is characterized by an x-ray powder diffraction (XRPD) pattern substantially as set forth in FIG. 5 .

6. The crystalline form of claim 3 2, wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II and 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 crystalline form of claim 3 2, wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II and is characterized by differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 8 .

8. The crystalline form of claim 3 2, wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II and is characterized by a dynamic vapor sorption (DVS) pattern substantially as set forth in FIG. 14 .

9. The crystalline form of claim 2 , wherein the crystalline form is Crystalline N-(cyanomethyl)-4-(2-(4-morpholino-phenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form I.

10. The crystalline form of claim 9 . 2, wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form I and is characterized by an x-ray powder diffraction (XRPD) pattern substantially as set forth in FIG. 6 .

11. The crystalline form of claim 9 2, wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form I and 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 crystalline form of claim 9 2, wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form I and is characterized by a differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 9 .

13. The crystalline form of claim 2 , wherein the crystalline form is crystalline N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrirnidin-4-yl)benzamide monohydrochloride anhydrous Form III.

14. The crystalline form of claim 13 2, wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form III and is characterized by an x-ray powder diffraction (XRPD) pattern substantially as set forth in FIG. 7 .

15. The crystalline form of claim 13 2, wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form III and is characterized by an X-ray powder diffraction (XRPD) pattern having peaks at about 12.7°, 14.6°, 17 , 8 °17.8°, 19.7°, and 23.3° 2−θ±0.2° 2−θ.

16. The crystalline form of claim 13 2, wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form III and is characterized by a differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 10 .

17. A pharmaceutical composition comprising a compound of claim 1 , wherein the pharmaceutical composition is in a solid form.

18. The pharmaceutical composition of claim 17 , wherein the compound of claim 1 is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II.

19. The pharmaceutical composition of claim 17 wherein N-(cyanornethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II is present at in an amount equivalent to 50 mg, 100 mg, 150 mg, or 200 mg of free base N-(cyanomethyl)-4-(2-(4-morpholinaphenybmino)pyrimidin-4-yl)benzamide N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide.

20. The pharmaceutical composition of claim 17 in the form of a tablet.

21. The pharmaceutical composition of claim 17 , wherein after a single oral administration said composition provides:

a C max in the range of 260 to 405 ng/mL of N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide,

an AUC inf in the range of 2,057 to 3,214 ng·hr/mL of N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide, or

both a C max in the range of 260 to 405 ng/ml of N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide and an AUC inf in the range of 2,057 to 3,214 ng·hr/mL of N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide.

22. The pharmaceutical composition of claim 21 , wherein after a single oral administration said composition provides a pharmacokinetic profile substantially similar to that of a dosage form comprising N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride anhydrous Form I in an amount equivalent to 300 mg of free base N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide.

23. A method for the treatment of a disease associated with Janus Kinase (JAK) which comprises administering to a subject in need an effective amount of the pharmaceutical composition of claim 18 , wherein the disease is a myeloproliferative disease selected from the group consisting of thrombocythemia, idiopathic myelofibrosis, systemic mastocystosis (SM), myelodispiastic myelodysplastic syndrome (MDS) and systemic mast cell disease (SMCD).

24. A pharmaceutical composition comprising a compound having the formula

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or diluent.

25. A pharmaceutical composition comprising a compound having the formula

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or diluent.

26. A pharmaceutical composition comprising a compound having the formula

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or diluent.