Salts and solid forms of (S)-3-(4- (4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and compositions comprising and methods of using the same
Salts and solid forms of 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a stereoisomer thereof, are disclosed. Compositions comprising and methods of using the salts and solid forms are also disclosed.
1. A solid form comprising a salt, hydrate, or solvate of Compound (I-S):
wherein the solid form is crystalline, wherein the solid form
comprises Compound (I-S) and water, having an XRPD pattern comprising peaks at approximately 8.31, 11.80, and 17.37 degrees 2θ;
comprises Compound (I-S) and THF, having an XRPD pattern comprising peaks at approximately 11.80, 20.89, and 22.16 degrees 2θ;
comprises a besylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 19.07, 20.71, and 23.96 degrees 2θ;
comprises a DMSO solvate of a besylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 16.88, 18.14, and 20.02 degrees 2θ;
comprises a D-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 17.00, 19.73, and 25.86 degrees 2θ;
comprises a hemi D-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 6.21, 12.91, and 16.32 degrees 2θ;
comprises a L-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 6.27, 10.90, and 15.32 degrees 2θ;
comprises a tosylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 9.77, 15.41, and 19.25 degrees 2θ; or
comprises a (+) camphorsulfonic acid salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 9.05, 14.61, and 16.82 degrees 2θ.
2. A solid form comprising a racemic Compound (I):
or a salt, hydrate, anhydrate, or solvate thereof, wherein the solid form is crystalline, wherein the solid form
comprises racemic Compound (I), having an XRPD pattern comprising peaks at approximately 4.95, 8.96, and 14.83 degrees 2θ;
comprises racemic Compound (I) and water, having an XRPD pattern comprising peaks at approximately 14.01, 17.28, and 26.21 degrees 2θ;
comprises a HCl salt of racemic Compound (I) and water, having an XRPD pattern comprising peaks at approximately 13.88, 14.30, and 15.36 degrees 2θ; or
comprises a HCl salt of racemic Compound (I) and methanol, having an XRPD pattern comprising peaks at approximately 12.38, 14.54, and 26.10 degrees 2θ.
3. The solid form of claim 1 , comprising Compound (I-S) and water having an XRPD pattern comprising peaks at approximately 8.31, 11.80, and 17.37 degrees 2θ.
4. The solid form of claim 3 , further comprises peaks at approximately 13.79, 17.15, and 26.00 degrees 2θ.
5. The solid form of claim 3 , comprising Compound (I-S) and water, wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 5 .
6. The solid form of claim 1 , comprising Compound (I-S) and THF having an XRPD pattern comprising peaks at approximately 11.80, 20.89, and 22.16 degrees 2θ.
7. The solid form of claim 6 , further comprises peaks at approximately 6.03 and 18.59 degrees 2θ.
8. The solid form of claim 6 , comprising Compound (I-S) and THF, wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 8 .
9. The solid form of claim 1 , comprising a besylate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 19.07, 20.71, and 23.96 degrees 2θ.
10. The solid form of claim 9 , further comprises peaks at approximately 15.48 and 15.92 degrees 2θ.
11. The solid form of claim 9 , comprising a besylate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 11 .
12. The solid form of claim 1 , comprising a DMSO solvate of a besylate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 16.88, 18.14, and 20.02 degrees 2θ.
13. The solid form of claim 12 , further comprises peaks at approximately 7.31 and 24.49 degrees 2θ.
14. The solid form of claim 12 , comprising a DMSO solvate of a besylate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 16 .
15. The solid form of claim 1 , comprising a D-tartrate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 17.00, 19.73, and 25.86 degrees 2θ.
16. The solid form of claim 15 , further comprises peaks at approximately 19.25 and 21.25 degrees 2θ.
17. The solid form of claim 15 , comprising a D-tartrate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 20 .
18. The solid form of claim 1 , comprising a hemi D-tartrate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 6.21, 12.91, and 16.32 degrees 2θ.
19. The solid form of claim 18 , further comprises peaks at approximately 12.32 and 19.09 degrees 2θ.
20. The solid form of claim 18 , comprising a hemi D-tartrate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 23 .
21. The solid form of claim 1 , comprising a L-tartrate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 6.27, 10.90, and 15.32 degrees 2θ.
22. The solid form of claim 21 , further comprises peaks at approximately 11.97, 14.41, and 17.08 degrees 2θ.
23. The solid form of claim 21 , comprising a L-tartrate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 26 .
24. The solid form of claim 1 , comprising a tosylate salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 9.77, 15.41, and 19.25 degrees 2θ.
25. The solid form of claim 24 , further comprises peaks at approximately 7.41 and 22.97 degrees 2θ.
26. The solid form of claim 24 , comprising a tosylate salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 29 .
27. The solid form of claim 1 , comprising a (+) camphorsulfonic acid salt of Compound (I-S) having an XRPD pattern comprising peaks at approximately 9.05, 14.61, and 16.82 degrees 2θ.
28. The solid form of claim 27 , further comprises peaks at approximately 13.97, 15.34, and 16.35 degrees 2θ.
29. The solid form of claim 27 , comprising a (+) camphorsulfonic acid salt of Compound (I-S), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 32 .
30. A solid form comprising a HCl salt of Compound (I-S):
or a salt, hydrate, anhydrate, or solvate of the HCl salt, wherein the solid form is crystalline, wherein the solid form
is Form A crystal form characterized by an XRPD pattern comprising peaks at approximately 15.09, 15.94, and 22.30 degrees 2θ;
is Form B crystal form characterized by an XRPD pattern comprising peaks at approximately 7.11, 14.20, and 20.71 degrees 2θ;
is Form C crystal form characterized by an XRPD pattern comprising peaks at approximately 6.55, 13.14, and 13.37 degrees 2θ;
is Form D crystal form characterized by an XRPD pattern comprising peaks at approximately 13.52, 14.16, and 25.00 degrees 2θ;
is Form E crystal form characterized by an XRPD pattern comprising peaks at approximately 9.82, 17.06, and 17.73 degrees 2θ;
is Form F crystal form characterized by an XRPD pattern comprising peaks at approximately 13.71, 14.22, and 20.87 degrees 2θ;
is Form G crystal form characterized by an XRPD pattern comprising peaks at approximately 6.85, 20.20, and 20.60 degrees 2θ;
is Form H crystal form characterized by an XRPD pattern comprising peaks at approximately 6.83, 20.19, and 20.58 degrees 2θ;
is Form I crystal form characterized by an XRPD pattern comprising peaks at approximately 13.95, 23.39, and 24.10 degrees 2θ;
is Form J crystal form characterized by an XRPD pattern comprising peaks at approximately 4.86, 13.48, and 20.06 degrees 2θ; or
is Form K crystal form characterized by an XRPD pattern comprising peaks at approximately 7.09, 14.03, and 14.22 degrees 2θ.
31. The solid form of claim 30 , wherein the solid form is Form A crystal form characterized by an XRPD pattern comprising peaks at approximately 15.09, 15.94, and 22.30 degrees 2θ.
32. The solid form of claim 31 , further comprises peaks at approximately 17.65, 22.47, and 26.77 degrees 2θ.
33. The solid form of claim 31 , wherein the solid form is Form A crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 36 .
34. The solid form of claim 31 , which exhibits a thermal event, as characterized by DSC, with a peak temperature of about 261° C. and an onset temperature of about 256° C.
35. The solid form of claim 31 , which exhibits a weight loss of about 0.16% of the total sample weight upon heating from about 25 to about 120° C.
36. The solid form of claim 30 , wherein the solid form is Form B crystal form characterized by an XRPD pattern comprising peaks at approximately 7.11, 14.20, and 20.71 degrees 2θ.
37. The solid form of claim 36 , further comprises peaks at approximately 9.93 and 21.36 degrees 2θ.
38. The solid form of claim 36 , wherein the solid form is Form B crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 44 .
39. The solid form of claim 30 , wherein the solid form is Form C crystal form characterized by an XRPD pattern comprising peaks at approximately 6.55, 13.14, and 13.37 degrees 2θ.
40. The solid form of claim 39 , further comprises peaks at approximately 9.09, 19.62, and 19.80 degrees 2θ.
41. The solid form of claim 39 , wherein the solid form is Form C crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 50 .
42. The solid form of claim 30 , wherein the solid form is Form D crystal form characterized by an XRPD pattern comprising peaks at approximately 13.52, 14.16, and 25.00 degrees 2θ.
43. The solid form of claim 42 , further comprises peaks at approximately 6.82, 8.07, and 15.71 degrees 2θ.
44. The solid form of claim 42 , wherein the solid form is Form D crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 57 .
45. The solid form of claim 30 , wherein the solid form is Form E crystal form characterized by an XRPD pattern comprising peaks at approximately 9.82, 17.06, and 17.73 degrees 2θ.
46. The solid form of claim 45 , further comprises peaks at approximately 16.05, 25.71, and 26.15 degrees 2θ.
47. The solid form of claim 45 , wherein the solid form is Form E crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 64 .
48. The solid form of claim 30 , wherein the solid form is Form F crystal form characterized by an XRPD pattern comprising peaks at approximately 13.71, 14.22, and 20.87 degrees 2θ.
49. The solid form of claim 48 , further comprises peaks at approximately 7.10, 16.35, and 28.36 degrees 2θ.
50. The solid form of claim 48 , wherein the solid form is Form F crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 73 .
51. The solid form of claim 30 , wherein the solid form is Form G crystal form characterized by an XRPD pattern comprising peaks at approximately 6.85, 20.20, and 20.60 degrees 2θ.
52. The solid form of claim 51 , further comprises peaks at approximately 9.56, 13.69, 19.05, and 23.57 degrees 2θ.
53. The solid form of claim 51 , wherein the solid form is Form G crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 82 .
54. The solid form of claim 30 , wherein the solid form is Form H crystal form characterized by an XRPD pattern comprising peaks at approximately 6.83, 20.19, and 20.58 degrees 2θ.
55. The solid form of claim 54 , further comprises peaks at approximately 9.47 and 13.63 degrees 2θ.
56. The solid form of claim 54 , wherein the solid form is Form H crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 86 .
57. The solid form of claim 30 , wherein the solid form is Form I crystal form characterized by an XRPD pattern comprising peaks at approximately 13.95, 23.39, and 24.10 degrees 2θ.
58. The solid form of claim 57 , further comprises peaks at approximately 13.51 and 24.30 degrees 2θ.
59. The solid form of claim 57 , wherein the solid form is Form I crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 90 .
60. The solid form of claim 30 , wherein the solid form is Form J crystal form characterized by an XRPD pattern comprising peaks at approximately 4.86, 13.48, and 20.06 degrees 2θ.
61. The solid form of claim 60 , further comprises peaks at approximately 20.39, 22.15, and 23.45 degrees 2θ.
62. The solid form of claim 60 , wherein the solid form is Form J crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 92 .
63. The solid form of claim 30 , wherein the solid form is Form K crystal form characterized by an XRPD pattern comprising peaks at approximately 7.09, 14.03, and 14.22 degrees 2θ.
64. The solid form of claim 63 , further comprises peaks at approximately 9.35 and 21.60 degrees 2θ.
65. The solid form of claim 63 , wherein the solid form is Form K crystal form characterized by an XRPD diffraction pattern which matches the XRPD diffraction pattern presented in FIG. 95 .
66. The solid form of claim 2 , comprising racemic Compound (I) having an XRPD pattern comprising peaks at approximately 4.95, 8.96, and 14.83 degrees 2θ.
67. The solid form of claim 66 , further comprises peaks at approximately 12.67, 14.30, 20.09, and 26.57 degrees 2θ.
68. The solid form of claim 66 , comprising racemic Compound (I), wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 97 .
69. The solid form of claim 2 , comprising racemic Compound (I) and water having an XRPD pattern comprising peaks at approximately 14.01, 17.28, and 26.21 degrees 2θ.
70. The solid form of claim 69 , further comprises peaks at approximately 8.34, 11.79, and 17.01 degrees 2θ.
71. The solid form of claim 69 , comprising racemic Compound (I) and water, wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 99 .
72. The solid form of claim 2 , comprising a HCl salt of racemic Compound (I) and water having an XRPD pattern comprising peaks at approximately 13.88, 14.30, and 15.36 degrees 2θ.
73. The solid form of claim 72 , further comprises peaks at approximately 9.84, 16.42, and 19.82 degrees 2θ.
74. The solid form of claim 72 , comprising a HCl salt of racemic Compound (I) and water, wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 101 .
75. The solid form of claim 2 , comprising a HCl salt of racemic Compound (I) and methanol having an XRPD pattern comprising peaks at approximately 12.38, 14.54, and 26.10 degrees 2θ.
76. The solid form of claim 75 , further comprises peaks at approximately 15.06, 20.00, and 26.86 degrees 2θ.
77. The solid form of claim 75 , comprising a HCl salt of racemic Compound (I) and methanol, wherein the solid form is characterized by an XRPD diffraction pattern which matches the XRPD pattern presented in FIG. 104 .