Solid forms of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-n-benzylacetamide
The present application provides solid forms of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide, and methods of preparing and using the same for the treatment of a cell proliferative disorder in which a tyrosine kinase plays a role.
1. A method of preparing a Form B polymorph of Compound A:
wherein
the Form B polymorph is characterized by having X-ray powder diffraction peaks at approximately 6.4, 19.3, and 19.9°2θ using Cu Kα radiation, wherein approximately refers to ±0.3°2θ, wherein the method comprises:
slurrying Compound A in chloroform.
2. A method of preparing the Form B polymorph of Compound A:
wherein
the Form B polymorph is characterized by having X-ray powder diffraction peaks at approximately 6.4, 19.3, and 19.9°2θ using Cu Kα radiation, wherein approximately refers to ±0.3°2θ, wherein the method comprises:
adding an anti-solvent to a solution of Compound A in chloroform or acetonitrile, wherein the anti-solvent is isopropyl alcohol;
adding an anti-solvent to a solution of Compound A in methanol, wherein the anti-solvent is isopropyl acetate;
adding an anti-solvent to a solution of Compound A in acetone, wherein the anti-solvent is toluene; or
allowing vapor of an anti-solvent to diffuse into a solution of Compound A in methanol or chloroform, wherein the anti-solvent is methyl tert-butyl ether.
3. The method of claim 2 , wherein the method comprises adding an anti-solvent to a solution of Compound A in chloroform wherein the anti-solvent is isopropyl alcohol.
4. The method of claim 2 , wherein the method comprises adding an anti-solvent to a solution of Compound A in acetonitrile, wherein the anti-solvent is isopropyl alcohol.
5. The method of claim 2 , wherein the method comprises adding an anti-solvent to a solution of Compound A in methanol, wherein the anti-solvent is isopropyl acetate.
6. The method of claim 2 , wherein the method comprises adding an anti-solvent to a solution of Compound A in acetone, wherein the anti-solvent is toluene.
7. The method of claim 2 , wherein the method comprises allowing vapor of an anti-solvent to diffuse into a solution of Compound A in methanol or chloroform, wherein the anti-solvent is methyl tert-butyl ether.
8. The method of claim 7 , wherein the method comprises allowing vapor of an anti-solvent to diffuse into a solution of Compound A in methanol, wherein the anti-solvent is methyl tert-butyl ether.
9. The method of claim 8 , wherein Compound A in methanol is at a concentration of about 14 g/mL.
10. The method of claim 7 , wherein the method comprises allowing vapor of an anti-solvent to diffuse into a solution of Compound A in chloroform, wherein the anti-solvent is methyl tert-butyl ether.
11. The method of claim 10 , wherein Compound A in chloroform is at a concentration of about 52 g/mL.
12. The method of claim 7 , wherein said vapor of said anti-solvent is allowed to diffuse into said solution of Compound A for about 7 days.
13. A method of preparing the Form B polymorph of Compound A:
wherein
the Form B polymorph is characterized by having X-ray powder diffraction peaks at approximately 6.4, 19.3, and 19.9°2θ using Cu Kα radiation, wherein approximately refers to ±0.3°2θ, wherein the method comprises:
slowly cooling a solution of Compound A in acetone, isopropyl acetate, 2-Me-THF, ethyl acetate, acetonitrile, a 1:3 mixture of chloroform and heptane, or a 1:3 mixture of dioxane and isopropyl acetate.
14. The method of claim 13 , wherein the method comprises: (i) heating a suspension of Compound A in acetone, isopropyl acetate, 2-Me-THF, ethyl acetate, acetonitrile, a 1:3 mixture of chloroform and heptane, or a 1:3 mixture of dioxane and isopropyl acetate, and (ii) slowly cooling the solution until the Form B polymorph precipitates from said solution.
15. The method of claim 14 , wherein the method comprises heating said suspension to a temperature of about 50° C.
16. The method of claim 13 , wherein the method comprises cooling said solution to a temperature of about 5° C.
17. The method of claim 13 , wherein the method comprises cooling said solution to a temperature of about −20° C.
18. The method of claim 1 , wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation, wherein approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6° 2 η refers to ±0.3°2θ.
19. The method of claim 1 , wherein the Form B polymorph of Compound A is characterized by an endothermic event with onset at between approximately 133° C. and approximately 138° C. as measured by DSC, wherein approximately 133° C. and approximately 138 ° C. refers to ±5% of the listed values.
20. The method of claim 2 , wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation, wherein approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6° 2 η C. refers refers to ±0.3°2θ.
21. The method of claim 2 , wherein the Form B polymorph of Compound A is characterized by an endothermic event with onset at between approximately 133° C. and approximately 138° C. as measured by DSC, wherein approximately 133° C. and approximately 138 ° C. 133° C. and approximately 138 ° C. refers to ±5% of the listed values.
22. The method of claim 13 , wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation, wherein approximately 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6° 2 η C. refers refers to ±0.3°2θ.
23. The method of claim 13 , wherein the Form B polymorph of Compound A is characterized by an endothermic event with onset at between approximately 133° C. and approximately 138° C. as measured by DSC, wherein approximately 133° C. and approximately 138 ° C. refers to ±5% of the listed values.
24. The method of claim 1 , wherein the Form B polymorph is characterized by having X-ray powder diffraction peaks at 6.4, 19.3, and 19.9°2θ using Cu Kα radiation.
25. The method of claim 1 , wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation.
26. The method of claim 2 , wherein the Form B polymorph is characterized by having X-ray powder diffraction peaks at 6.4, 19.3, and 19.9°2θ using Cu Kα radiation.
27. The method of claim 2 , wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation.
28. The method of claim 13 , wherein the Form B polymorph is characterized by having X-ray powder diffraction peaks at 6.4, 19.3, and 19.9°2θ using Cu Kα radiation.
29. The method of claim 13 , wherein the Form B polymorph of Compound A is characterized by having X-ray powder diffraction peaks at 6.4, 7.2, 19.3, 19.9, 21.6, 22.1, and 22.6°2θ using Cu Kα radiation.