Claims for Patent: 10,519,142

Summary for Patent: 10,519,142

Title:	Crystalline forms of 6-((6,7-dimethoxyquinazolin-4-yl)oxy)-N,2-dimethylbenzofuran-3-carboxamide
Abstract:	The present invention relates to the pharmaceutical field, provides novel crystalline forms, solvates and the crystalline forms thereof of compound 6-((6,7-dimethoxyquinazolin-4-yl)oxy)-N,2-dimethylbenzofuran-3-carboxamide, pharmaceutical compositions, as well as the methods of preparation and the use thereof.
Inventor(s):	Wu Zhenping, Li Wenji, Chu Yuping
Assignee:	HUTCHISON MEDIPHARMA LIMITED
Application Number:	US15510631
Patent Claims:	5. A method of preparing the Form I according to claim 2 , comprising:{'sub': '3-6', '(1) mixing compound 6-((6,7-dimethoxyquinazolin-4-yl)oxy)-N,2-dimethylbenzofuran--carboxamide with at least one dissolution solvent or dissolution solvent mixture, and heating the mixture to reflux to obtain a solution; wherein, said at least one dissolution solvent is selected from methanol, Calkanol, acetic acid, and aprotic solvent; said dissolution solvent mixture is selected from a mixture of two or more aprotic solvents, or a mixture of water miscible organic solvent and water, in which the volume percentage of the water miscible organic solvent in said dissolution solvent mixture is less than about 50%;'}(2) cooling the solution obtained in step (1) to ambient temperature;(3) isolating to obtain the solid of Form I of 6-((6,7-dimethoxyquinazolin-4-yl)oxy)-N,2-dimethylbenzofuran-3-carboxamide, wherein an X-ray powder diffractogram of the Form I comprises diffraction angles expressed in degrees 2-theta (2θ) at:5.3, 10.7, 13.9, and 14.6, each of the diffraction angles having an error of about ±0.2degrees (2θ); and(4) drying the solid obtained in step (3).6. The method of claim 5 , wherein the dissolution solvent is acetone.7. The Form I according to claim 2 , wherein an X-ray powder diffractogram of the Form I comprises diffraction angles (2θ) of 5.3 claim 2 , 7.3 claim 2 , 10.7 claim 2 , 13.9 claim 2 , 14.6 claim 2 , 19.9 degrees claim 2 , each of the diffraction angles having an error of about ±0.2 degrees (2θ).8. The Form I according to claim 2 , wherein an X-ray powder diffractogram of the Form I comprises diffraction angles (2θ) of 5.3 claim 2 , 7.3 claim 2 , 10.7 claim 2 , 13.9 claim 2 , 14.6 claim 2 , 16.3 claim 2 , 19.9 degrees claim 2 , each of the diffraction angles having an error of about ±0.2 degrees (2θ).9. The Form I according to claim 2 , wherein an X-ray powder diffractogram of the Form I comprises diffraction angles (2θ) of 5.3 claim 2 , 7.3 claim 2 , 10.7 claim 2 , 13.9 claim 2 , 14.6 claim 2 , 16.3 claim 2 , 19.9 claim 2 , 21.1 claim 2 , 21.3 claim 2 , and 25.8 degrees claim 2 , each of the diffraction angles having an error of about ±0.2 degrees (2θ).10. The Form I according to claim 2 , wherein an X-ray powder diffractogram of the Form I comprises diffraction angles (2θ) of 5.3 claim 2 , 7.3 claim 2 , 10.7 claim 2 , 13.9 claim 2 , 14.6 claim 2 , 15.2 claim 2 , 16.3 claim 2 , 19.9 claim 2 , 21.1 claim 2 , 21.3 claim 2 , 23.1 claim 2 , 23.3 claim 2 , and 25.8 degrees claim 2 , each of the diffraction angles having an error of about ±0.2 degrees (2θ).11. The Form I according to claim 2 , wherein the Form I has an X-ray powder diffractogram having diffraction angles (2θ) as shown in claim 2 , each of the diffraction angles having an error of about ±0.2 degrees (2θ).12. A method of preparing the Form I according to claim 2 , comprising:(1) mixing compound 6-((6,7-dimethoxyquinazolin-4-yl)oxy)-N,2-dimethylbenzofuran-3-carboxamide with at least one dissolution solvent, then heating the mixture to reflux to obtain the first solution; wherein said dissolution solvent is selected from ethanol, isopropanol, acetone, dichloromethane, dimethyl sulfoxide, and N,N-dimethylformamide;(2) adding at least one anti-dissolution solvent to said first solution to obtain the second solution;(3) allowing the second solution to cool to ambient temperature; then(4) isolating to obtain the solid of Form I of 6-((6,7-dimethoxyquinazolin-4-yl)oxy)-N,2-dimethylbenzofuran-3-carboxamide wherein an X-ray powder diffractogram of the Form I comprises diffraction angles expressed in degrees 2-theta (2θ) at: 5.3, 10.7, 13.9, and 14.6, each of the diffraction angles having an error of about ±0.2 degrees (2θ); and(5) drying the solid obtained in step (4).13. A method of preparing the Form I according to claim 2 , comprising:(1) suspending a solid of compound 6-((6,7-dimethoxyquinazolin-4-yl)oxy)-N, 2-dimethylbenzofuran-3-carboxamide in an appropriate amount of a solvent system; wherein, said solvent system is selected from dissolution solvent, or a solvent mixture of water miscible organic solvent and water, in which volume percentage of water miscible organic solvent in the solvent mixture is less than about 80%;(2) stirring the suspension obtained in step (1);(3) isolating to obtain the solid of the Form I of 6-((6,7-dimethoxyquinazolin-4-yl)oxy)-N,2-dimethylbenzofuran-3-carboxamide, wherein an X-ray powder diffractogram of the Form I comprises diffraction angles expressed in degrees 2-theta (2θ) at: 5.3, 10.7, 13.9, and 14.6, each of the diffraction angles having an error of about ±0.2 degrees (2θ); and(4) drying the solid obtained in step (3).15. The pharmaceutical composition according to claim 14 , wherein the content of other crystalline forms of the compound of Formula A in said pharmaceutical composition is less than 30% by weight.16. The pharmaceutical composition according to claim 14 , wherein the content of other crystalline forms of the compound of Formula A in said pharmaceutical composition is less than 20% by weight.17. The pharmaceutical composition according to claim 14 , wherein the content of other crystalline forms of the compound of Formula A in said pharmaceutical composition is less than 10% by weight.18. The pharmaceutical composition according to claim 14 , wherein the content of other crystalline forms of the compound of Formula A in said pharmaceutical composition is less than 5% by weight.19. The pharmaceutical composition according to claim 14 , wherein the content of other crystalline forms of the compound of Formula A in said pharmaceutical composition is less than 1% by weight.20. A method of treating colorectal cancer in a subject in recognized need thereof claim 14 , comprising administering to said subject an effective amount for treating colorectal cancer of the pharmaceutical composition of .