Pyrrolopyrimidine crystal for preparing JAK inhibitor

• US 10,626,118 B2
• Filed: 06/15/2017
• Issued: 04/21/2020
• Est. Priority Date: 06/16/2016
• Status: Active Grant

• Current Assignee: Centaurus Biopharma Co., Ltd., Chia Tai Tianqing Pharmaceutical Group Co. Ltd. (SINO Biopharmaceutical Limited), Lianyungang Runzhong Pharmaceutical Co., Ltd. (SINO Biopharmaceutical Limited)
• Original Assignee: Chia Tai Tianqing Pharmaceutical Group Co. Ltd. (SINO Biopharmaceutical Limited)
• Inventors: Zhou, Zhou, Zhang, Aiming, Zhang, Xiquan, Yao, Huadong
• Primary Examiner(s): Rao, Deepak R
• Application Number:
  US16/310,369
• Publication Number:
  US 20190330215A1
• Time in Patent Office: 1,041 Days
• Field of Search: 544280, 5142651
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B01D 9/005 Selection of auxiliary, e.g. for control of crystallisation nuclei, of crystal growth, of adherence to walls; Arrangements for introduction thereof
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The present application relates to the field of pharmaceutical chemistry. The application specifically relates to a crystal form A and crystal form B of a pyrrolopyrimidine (formula I) for preparing a JAK inhibitor. The application further relates to a method for preparing the crystal form A and crystal form B, a crystalline composition comprising the crystal form A or crystal form B, a pharmaceutical composition comprising the crystal form A, crystal form B, or crystalline composition, and a pharmaceutical application of the pharmaceutical composition, the crystal form A, and the crystal form B. The crystal form A and crystal form B of the application has the advantages of high purity, high crystallinity, and good stability.

Claims

1. A crystal A of a compound represented by formula I:

2. A method for preparing the crystal A of the compound represented by formula I according to claim 1, comprising the following steps:

1) dissolving the compound represented by formula I in a crystallization solvent, wherein the crystallization solvent is selected from methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, ethylene glycol monomethyl ether, diethyl ether, isopropyl ether, methyl t-butyl ether, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, acetone, 1-butanone, 2-butanone, ethyl acetate, ethyl formate, methyl acetate, isopropyl acetate, dichloromethane, chloroform, water, or a mixed solvent of any two or more of the above solvents; and

2) crystallizing the compound represented by formula I.

3. The method according to claim 2, wherein the crystallization solvent is ethanol, isopropyl ether, ethyl acetate, acetone, dichloromethane, water, or a mixed solvent of any two or more of the above solvents.

4. A crystalline composition, wherein the crystal A of the compound represented by formula I according to claim 1 accounts for 50% or more, by weight of the crystalline composition.

5. A pharmaceutical composition, comprising an effective amount of the crystal A of the compound represented by formula I according to claim 1.

6. A method for treating a Janus kinase-mediated disease, comprising administering to a mammal in need thereof a therapeutically effective amount of the crystal A of the compound represented by formula I according to claim 1, wherein the Janus kinase-mediated disease is lymphoma or leukemia.

17. The crystal A of the compound represented by formula I according to claim 1, wherein an X-ray diffraction pattern of the crystal A of the compound represented by formula I has diffraction peaks at 2θ

of 9.35°

±

0.2°

, 11.93°

±

0.2°

, 16.32°

±

0.2°

, 18.82°

±

0.2°

, 20.54°

±

0.2°

, 21.23°

±

0.2°

, 23.13°

±

0.2° and

25.58°

±

0.2°

.

18. The crystal A of the compound represented by formula I according to claim 1, wherein an X-ray diffraction pattern of the crystal A of the compound represented by formula I has diffraction peaks at 2θ

of 9.35°

±

0.2°

, 10.93°

±

0.2°

, 11.93°

±

0.2°

, 14.46°

±

0.2°

, 16.32°

±

0.2°

, 18.82°

±

0.2°

, 20.54°

±

0.2°

, 21.23°

±

0.2°

, 21.66°

±

0.2°

, 23.13°

±

0.2°

, 25.58°

±

0.2° and

26.34°

±

0.2°

.

7. A crystal B of a compound represented by formula I:

8. The crystal B of the compound represented by formula I according to claim 7 which is an acetonitrilate of the compound represented by formula I, wherein a molar ratio of the compound represented by formula I to acetonitrile is in the range of 1:

0.5 to 1;

2.0.

9. A method for preparing the crystal B of the compound represented by formula I according to claim 7, comprising the following steps:

1) dissolving the compound represented by formula I in acetonitrile; and

2) crystallizing the compound represented by formula I.

10. A crystalline composition, wherein the crystal B of the compound represented by formula I according to claim 7 accounts for 50% or more, by weight of the crystalline composition.

11. A pharmaceutical composition, comprising an effective amount of the crystal B of the compound represented by formula I according to claim 7.

12. A method for treating a Janus kinase-mediated disease, comprising administering to a mammal in need thereof a therapeutically effective amount of the crystal B of the compound represented by formula I according to claim 7, wherein the Janus kinase-mediated disease is lymphoma or leukemia.

13. A method for preparing the crystal B of the compound represented by formula I according to claim 8, comprising the following steps:

1) dissolving the compound represented by formula I in acetonitrile; and

2) crystallizing the compound represented by formula I.

14. A crystalline composition, wherein the crystal B of the compound represented by formula I according to claim 8 accounts for 50% or more, by weight of the crystalline composition.

15. A pharmaceutical composition, comprising an effective amount of the crystal B of the compound represented by formula I according to claim 8.

16. A method for treating a Janus kinase-mediated disease, comprising administering to a mammal in need thereof a therapeutically effective amount of the crystal B of the compound represented by formula I according to claim 8, wherein the Janus kinase-mediated disease is lymphoma or leukemia.

19. The crystal B of the compound represented by formula I according to claim 7, wherein an X-ray diffraction pattern of the crystal B of the compound represented by formula I has diffraction peaks at 2θ

of 8.97°

±

0.2°

, 9.39°

±

0.2°

, 12.90°

±

0.2°

, 16.54°

±

0.2°

, 17.70°

±

0.2°

, 19.20°

±

0.2°

, 20.31°

±

0.2°

, 22.78°

±

0.2° and

23.63°

±

0.2°

.

20. The crystal B of the compound represented by formula I according to claim 7 which is an acetonitrilate of the compound represented by formula I, wherein a molar ratio of the compound represented by formula I to acetonitrile is in the range of 1:

1.