Crystalline of compound as c-Met kinase inhibitor and preparation method therefor and use thereof

Patent metadata

Field	Value
Publication number	US-11279676-B2
Application number	US-201916977054-A
Country	US
Kind code	B2
Filing date	Mar 1, 2019
Priority date	Mar 2, 2018
Publication date	Mar 22, 2022
Grant date	Mar 22, 2022

Abstract

The present application falls within the field of medicinal chemistry, relates to the crystalline of a compound as a c-Met kinase inhibitor, and specifically relates to the crystalline of N-(4-((7-((1-(cyclopentylamino)cyclopropyl)methoxy)-6-methoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and a preparation method therefor, a crystalline composition thereof, and a pharmaceutical composition thereof, as well as the use of the crystalline for treating diseases associated with the inhibition of growth factor receptor protein tyrosine kinase activity. The crystalline of the present application has excellent properties in at least one of the following aspects: pharmacokinetics, bioavailability, hygroscopicity, stability, solubility, purity, ease of preparation, etc.

First claim

What is claimed:

1. A crystalline form of the compound of formula I,

having a Cu Kα radiation X ray powder diffraction pattern with diffraction peaks present at 2θ angles comprising about 13.38, 15.71, 16.47, 20.15, 20.86, and 21.43 degrees, about 9.25, 10.45, 13.38, 14.03, 15.71, 16.47, 17.20, 17.85, 18.16, 18.48, 19.80, 20.15, 20.86, 21.43, 22.53, 23.43 and 24.87 degrees, about 9.25, 10.45, 12.48, 13.38, 14.03, 15.71, 16.47, 17.20, 17.85, 18.16, 18.48, 18.85, 19.80, 20.15, 20.86, 21.43, 21.79, 22.53, 23.43, 24.87, 25.47 and 29.07 degrees, or about 9.25, 9.64, 10.45, 11.27, 12.48, 13.38, 14.03, 15.71, 16.47, 17.20, 17.85, 18.16, 18.48, 18.85, 19.80, 20.15, 20.86, 21.43, 21.79, 22.53, 23.43, 24.25, 24.87, 25.47, 26.54, 26.76, 27.78, 29.07, 30.51, 31.99, 33.01, 34.65, 35.10 and 36.00 degrees.

2. A method for preparing the crystalline compound of claim 1 , comprising the following steps of:
(1) mixing the compound of formula I and solvent A to obtain a solution of the compound of formula I; and
(2) precipitating solid;
wherein the solvent A in step (1) comprises toluene, butanone, acetonitrile, acetonitrile and water, ethyl acetate and toluene, or acetonitrile and toluene.

3. A crystalline form of the compound of formula I,

having a Cu Kα radiation X ray powder diffraction pattern with diffraction peaks present at 2θ angles comprising about 7.44, 8.93, 10.44 and 17.84 degrees, about 7.44, 8.93, 10.26, 10.44, 10.70, 11.17, 12.65, 12.96, 14.35, 15.49, 16.34, 17.84, 18.28, 18.73, 20.96, 21.88, 22.42, 23.03, 24.17, 25.27 and 26.16 degrees, or about 7.44, 8.93, 9.48, 10.26, 10.44, 10.70, 11.17, 11.85, 12.65, 12.96, 13.57, 14.35, 15.49, 15.75, 16.34, 17.84, 18.28, 18.73, 19.43, 20.02, 20.65, 20.96, 21.88, 22.42, 23.03, 24.17, 25.27, 25.99, 26.16 and 29.24 degrees.

4. A method for preparing the crystalline compound of claim 3 comprising the following steps of:
(1) mixing the compound of formula I and solvent B to obtain a solution of the compound of formula I; and
(2) precipitating solid;
wherein the solvent B in step (1) is selected from methanol, ethanol, acetone, a mixed solvent of methanol and water, a mixed solvent of ethanol and water, a mixed solvent of acetone and water, or a mixed solvent of ethanol and butanone;
wherein the volume fraction of methanol in the mixed solvent of methanol and water is 95%;
wherein the volume fraction of ethanol in the mixed solvent of ethanol and water is 65%-95%;
wherein the volume fraction of acetone in the mixed solvent of acetone and water is 65%-95%;
wherein the volume fraction of butanone in the mixed solvent of ethanol and butanone is not more than 30%.

5. A crystalline form of the compound of formula I,

having a Cu Kα radiation X ray powder diffraction pattern with diffraction peaks are present at 2θ angles comprising about 7.38, 10.33 and 17.84 degrees, about 7.38, 8.80, 10.33, 11.15, 15.30, 17.84, 18.18, 19.76, 21.03 and 21.86 degrees, or about 7.38, 8.80, 10.33, 11.15, 11.71, 12.33, 12.58, 12.88, 13.50, 14.28, 15.30, 16.04, 16.33, 16.55, 17.84, 18.18, 18.43, 19.76, 21.03, 21.86, 22.83, 25.34 and 25.86 degrees.

6. A method for preparing the crystalline compound of claim 5 comprising the following steps of:
(1) mixing the compound of formula I and solvent C to obtain a solution of the compound of formula I; and
(2) precipitating solid;
wherein the solvent C in step (1) is dioxane.

7. A composition comprising the crystalline compound of claim 1 .

8. A pharmaceutical composition comprising a therapeutically effective amount of a crystalline of the compound of formula I,

wherein the crystalline of the compound of formula I is the crystalline form of the compound of formula I according to claim 1 .

9. A method of treating diseases mediated by c-Met kinase comprising administering an effective amount of the composition of claim 8 to a patient, wherein the disease mediated by c-Met kinase is cancer.

10. The method of claim 1 , wherein the disease mediated by c-Met kinase is lung cancer.

11. A composition comprising the crystalline compound of claim 3 .

12. A pharmaceutical composition comprising a therapeutically effective amount of a crystalline of the compound of formula I,

wherein the crystalline of the compound of formula I is the crystalline form of the compound of formula I according to claim 3 .

13. A method of treating diseases mediated by c-Met kinase comprising administering an effective amount of the composition of claim 12 to a patient, wherein the disease mediated by c-Met kinase is cancer.

14. The method of claim 13 , wherein the disease mediated by c-Met kinase is lung cancer.

15. A composition comprising the crystalline compound of claim 5 .

16. A pharmaceutical composition comprising a therapeutically effective amount of a crystalline of the compound of formula I,

wherein the crystalline of the compound of formula I is the crystalline form of the compound of formula I according to claim 5 .

17. A method of treating diseases mediated by c-Met kinase comprising administering an effective amount of the composition of claim 16 to a patient, wherein the disease mediated by c-Met kinase is cancer.

18. The method of claim 17 , wherein the disease mediated by c-Met kinase is lung cancer.

Assignees

• Chia Tai Tianqing Pharmaceutical Group Co Ltd
• Advenchen Laboratories Nanjing Ltd

Inventors

• Gong Feng
• Huang Ticong
• Zang Haishan
• Zhang Shibo
• Zhao Rui
• Liu Fei

Classifications

• C07D215/233 Primary

  only one oxygen atom which is attached in position 4 · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title