Crystal form A of 2-butoxy-7-(4-(pyrrolidin-1-ylmethyl)benzyl)-5H-pyrrolo[3,2-D] pyrimidin-4-amine, preparation process and use thereof

• US 10,442,811 B2
• Filed: 02/04/2017
• Issued: 10/15/2019
• Est. Priority Date: 02/05/2016
• Status: Active Grant

• Current Assignee: Chia Tai Tianqing Pharmaceutical Group Co. Ltd. (SINO Biopharmaceutical Limited)
• Original Assignee: Chia Tai Tianqing Pharmaceutical Group Co. Ltd. (SINO Biopharmaceutical Limited)
• Inventors: Ding, Zhaozhong, Sun, Fei, Hu, Yinghu, Zhou, Yilong, Wang, Zheng, Zhao, Rui, Yang, Ling
• Primary Examiner(s): Willis, Douglas M
• Application Number:
  US16/075,297
• Publication Number:
  US 20190040071A1
• Time in Patent Office: 983 Days
• Field of Search: 5142651, 544280
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The present invention relates to crystalline form A of a TLR7 agonist 2-butoxy-7-(4-(pyrrolidin-1-ylmethyl)-benzyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine (formula I), a method for preparing the crystalline form A, and the use thereof.

Claims

1. A crystal form A of a compound of formula I:

2. The crystal form A according to claim 1, wherein the crystal form A is further characterized by a differential scanning calorimetry thermogram having an initial temperature of 199.0°

C.±

5°

C. and a peak temperature of 200.4°

C.±

5°

C.

3. A composition comprising a carrier or excipient and at least 95% w/w of the crystal form A according to claim 1, based on a total weight of the composition.

4. A composition comprising a carrier or excipient and at least 90% w/w of the crystal form A according to claim 1, based on a total weight of the composition.

5. A composition comprising a carrier or excipient and at least 80% w/w of the crystal form A according to claim 1, based on a total weight of the composition.

6. A composition comprising a carrier or excipient and at least 50% w/w of the crystal form A according to claim 1, based on a total weight of the composition.

7. The composition according to claim 6, wherein the carrier or excipient is a pharmaceutically acceptable carrier or excipient.

8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a therapeutically effective amount of the crystal form A according to claim 1.

9. A method for inhibiting toll-like receptor activity in a subject, wherein the method comprises administering to the subject in need thereof a therapeutically effective amount of the crystal form A according to claim 1.

10. The method according to claim 9, wherein the subject has a viral infection.

11. A method for inhibiting toll-like receptor activity in a subject, wherein the method comprises administering to the subject in need thereof a therapeutically effective amount of the composition according to claim 6.

12. The method according to claim 11, wherein the subject has a viral infection.

13. A method for inhibiting toll-like receptor activity in a subject, wherein the method comprises administering to the subject in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 8.

14. The method according to claim 13, wherein the subject has a viral infection.

15. A process for preparing the crystal form A according to claim 1, wherein the process comprises the following steps:

1) dissolving the compound of formula I according to claim 1 in a crystallizing solvent to form a solution, wherein the crystallizing solvent is selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, acetone, ethyl acetate and water, or a co-solvent mixture of any two or more thereof;

2) heating the solution of step

     1) to reflux while stirring;

3) cooling the solution of step

     2) to room temperature;

4) filtering the solution of step

     3) to obtain a filter cake; and

5) drying the filter cake of step

     4) to obtain the crystal form A according to claim 1.

16. The process according to claim 15, wherein the crystallizing solvent in step 1) is ethanol.

17. The process according to claim 15, wherein in step 1), the amount of crystallizing solvent added per gram of the compound of formula I is 2 mL to 10 mL.

18. The process according to claim 15, wherein in step 1), the amount of crystallizing solvent added per gram of the compound of formula I is 4 mL to 8 mL.

19. The process according to claim 15, wherein in step 1), the amount of crystallizing solvent added per gram of the compound of formula I is 5 mL to 7 mL.

20. A crystal form A of a compound of formula I: