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 Form A polymorph of Compound A:
is characterized by having X-ray powder diffraction peaks at approximately 4.3, 17.0, and 21.1° 2θ using Cu Kα radiation.
2 . The Form A polymorph of claim 1 , characterized by having X-ray powder diffraction peaks at approximately 4.3, 6.4, 8.6, 12.7, 17.0, and 21.1° 2θ using Cu Kα radiation.
3 . The Form A polymorph of claim 1 , characterized by having an X-ray powder diffraction pattern substantially similar to that set forth in FIG. 1 , 5 , 7 , 9 , 11 , 13 , or 18 .
4 . The Form A polymorph of claim 1 , characterized by an endothermic event with onset at between approximately 124° C. and approximately 135° C. as measured by DSC.
5 . The Form A polymorph of claim 1 , characterized by an endothermic event with onset at between approximately 135° C. and approximately 139° C. as measured by DSC.
6 . The Form A polymorph of claim 1 , characterized by endothermic events with onset at between approximately 124° C. and approximately 135° C., and between approximately 135° C. and approximately 139° C., as measured by DSC.
7 . The Form A polymorph of claim 1 , characterized by a DSC thermogram substantially similar to that set forth in FIG. 12 or 14 .
8 . The Form A polymorph of claim 1 , characterized by a weight loss of approximately 0.36% between about 33° C. and about 150° C., as measured by TGA.
9 - 13 . (canceled)
14 . A pharmaceutical composition comprising the Form A polymorph of claim 1 and a pharmaceutically acceptable carrier or excipient.
15 . A method of preparing the Form A polymorph of claim 1 , comprising:
allowing vapor of an anti-solvent to diffuse into a concentrated solution of Compound A in methanol or ethanol;
slowly cooling a solution of Compound A in isopropanol, a mixture of THF and water, or a mixture of acetone and MTBE; or
adding an anti-solvent to a solution of Compound A in chloroform, methanol, acetone, tetrahydrofuran, dioxane, ethanol, 2-Me-THF, ethyl acetate, or dichloromethane.
16 . (canceled)
17 . (canceled)
18 . A method of treating or preventing a disease or condition in which an Src tyrosine kinase plays a role, comprising administering to a subject in need thereof the Form A polymorph of claim 1 .
19 . The method of claim 15 , wherein the method comprises:
a) allowing vapor of an anti-solvent to diffuse into a concentrated solution of Compound A in methanol or ethanol, wherein the anti-solvent is hexane.
20 . The method of claim 15 , comprising adding an anti-solvent to a solution of Compound A in chloroform, methanol, acetone, tetrahydrofuran, dioxane, ethanol, 2-Me-THF, ethyl acetate, or dichloromethane, wherein the anti-solvent is selected from the group consisting of MTBE, water, heptane, isopropanol, MIBK, isopropyl acetate, and toluene.
21 . The method of claim 16 , wherein:
a) chloroform is the solvent and MTBE is the anti-solvent;
b) methanol is the solvent and water is the anti-solvent;
c) acetone is the solvent and heptane is the antisolvent;
d) tetrahydrofuran is the solvent and MTBE is the anti-solvent;
e) dioxane is the solvent and MIBK is the anti-solvent;
f) ethanol is the solvent and isopropyl acetate is the anti-solvent;
g) 2-Me-THF is the solvent and toluene is the anti-solvent;
h) ethyl acetate is the solvent and MIBK is the anti-solvent; or
i) dichloromethane is the solvent and MIBK is the anti-solvent.
22 . The method of claim 15 , comprising:
a) slowly cooling a solution of Compound A in a mixture of THF and water; or
b) slowly cooling a solution of Compound A in a mixture of acetone and MTBE.
23 . The method of claim 18 , wherein disease or condition is a cell proliferative disorder.
24 . The method of claim 18 , wherein the disease or condition is actinic keratosis.
25 . The method of claim 24 , wherein the Form A polymorph is characterized by having X-ray powder diffraction peaks at 4.3, 6.4, 8.6, 12.7, 17.0, and 21.1° 2θ using Cu Kα radiation and an endothermic event with an onset at 128° C. and/or 138° C. as measured by DSC.
26 . The Form A polymorph of claim 1 , characterized by having X-ray powder diffraction peaks at 4.3, 17.0, and 21.1° 2θ using Cu Kα radiation and an endothermic event with an onset at 128° C. and/or 138° C. as measured by DSC.
27 . The Form A polymorph of claim 1 , characterized by having X-ray powder diffraction peaks at 4.3, 6.4, 8.6, 12.7, 17.0, and 21.1° 2θ using Cu Kα radiation and an endothermic event with an onset at 128° C. and/or 138° C. as measured by DSC.