Process for making crystalline 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile
The present disclosure provides crystalline forms of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile, pharmaceutical compositions comprising the crystalline forms, methods of using the crystalline forms, and processes for making the crystalline forms.
1. A process for making a crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile of the formula (I):
wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile is characterized by a X-ray powder diffraction pattern comprising at least one characteristic peak (° 2θ) at 5.34°±0.2° 2θ, 10.68°±0.2° 2θ, 14.26°±0.2° 2θ, 16.06°±0.2° 2θ, 16.39°±0.2° 2θ, 16.48°±0.2° 2θ, 18.26°±0.2° 2θ, 18.65°±0.2° 2θ, 21.05°±0.2° 2θ, 21.76°±0.2° 2θ, 22.68°±0.2° 2θ, or 26.75°±0.2° 2θ;
wherein the X-ray powder diffraction pattern is determined on a diffractometer using CuKα radiation; and
wherein the process comprises the following steps:
(1) adding 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile to a solvent selected from the group consisting of a C 2-5 alkyl nitrile, a C 3-9 alkyl ketone, a C 2-8 alkyl acetate, a C 1-5 alcohol, a C 2-8 alkyl ether, and an aromatic solvent, or a mixture thereof;
wherein the solvent, or mixture thereof, has a water activity of less than 0.7; and
(2) crystallizing a crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile from the solvent above.
2. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile is characterized by a X-ray powder diffraction pattern comprising characteristic peaks (° 2θ) at 10.68°±0.2° 2θ and 18.65°±0.2° 2θ.
3. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile is characterized by a X-ray powder diffraction pattern comprising characteristic peaks (° 2θ) at 18.65°±0.2° 2θ and 21.76°±0.2° 2θ.
4. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile is characterized by a X-ray powder diffraction pattern comprising characteristic peaks (° 2θ) at 18.65°±0.2° 2θ and 22.68°±0.2° 2θ.
5. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile is characterized by a X-ray powder diffraction pattern comprising characteristic peaks (° 2θ) at 21.76°±0.2° 2θ and 26.75°±0.2° 2θ.
6. The process of claim 1 , wherein the solvent, or mixture thereof, is a mixture of acetone and heptane having a water activity of less than 0.7.
7. The process of claim 1 , wherein the solvent, or mixture thereof, has a water activity of less than about 0.5.
8. The process of claim 1 , wherein the crystallization of the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile is from acetonitrile having a water activity of less than 0.7.
9. The process of claim 1 , wherein the crystallization of the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile is from acetonitrile having a water activity of less than 0.5.
10. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-ye-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile resulting from the crystallization has a polymorphic purity of greater than 90%.
11. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-ye-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile resulting from the crystallization has a polymorphic purity of greater than 97%.
12. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-ye-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile resulting from the crystallization has a polymorphic purity of greater than 99%.
13. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-ye-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile resulting from the crystallization has a polymorphic purity of greater than 99.5%.
14. The process of claim 13 , wherein the acetonitrile:water ratio (v/v) is in the range of 92:8 to 97:3.
15. The process of claim 13 , wherein the acetonitrile:water ratio (v/v) is in the range of 95:5 to 97:3.
16. The process of claim 13 , wherein the acetonitrile:water ratio (v/v) is 96:4.
17. The process of claim 1 , wherein the solvent, or mixture thereof, has a water activity of less than 0.5.
18. The process of claim 1 , wherein the solvent, or mixture thereof, is a mixture of acetone and heptane having a water activity of less than 0.7.
19. The process of claim 1 , wherein the crystallization of the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile is from acetonitrile having a water activity of less than 0.7.
20. The process of claim 1 , wherein the crystallization of the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile is from acetonitrile having a water activity of less than 0.5.
21. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile resulting from the crystallization has a polymorphic purity of greater than 90%.
22. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile resulting from the crystallization has a polymorphic purity of greater than 97%.
23. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile resulting from the crystallization has a polymorphic purity of greater than 99%.
24. The process of claim 1 , wherein the crystalline form of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidin-3-yl)acetonitrile resulting from the crystallization has a polymorphic purity of greater than 99.5%.