Solid forms, pharmaceutical compositions and preparation of heteroaromatic macrocyclic ether compounds
Provided herein are solid forms comprising a compound of formula (I), or a stereoisomer, or a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof. Also provided herein are methods of synthesizing a compound of formula (I), pharmaceutical compositions comprising the same, and methods of treating, preventing, and managing various disorders using the compositions provided herein.
1. A solid form comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof:
wherein:
(a) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.7, 15.0, and 21.2° 2θ±0.2° 2θ;
(b) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 8.6, 14.0, and 20.8° 2θ±0.2° 2θ;
(c) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 13.4, 19.5, and 20.9° 2θ±0.2° 2θ;
(d) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 12.1, 12.7, and 18.4° 2θ±0.2° 2θ;
(e) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.5, 10.8, and 21.9° 2θ±0.2° 2θ;
(f) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 8.6, 18.7, and 20.5° 2θ±0.2° 2θ;
(g) the solid form comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 12.5, 13.4, and 14.6° 2θ±0.2° 2θ;
(h) the solid form comprises a besylate salt of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 15.0, 17.9 and 23.0° 2θ±0.2° 2θ; or
(i) the solid form comprises a phosphate salt of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.8, 18.5, and 24.8° 2θ±0.2° 2θ.
2. The solid form of claim 1 , which comprises a free base of a compound formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.7, 15.0, and 21.2° 2θ±0.2° 2θ.
3. The solid form of claim 2 , wherein the XRPD pattern further comprises peaks at 17.4 and 21.3° 2θ±0.2° 2θ.
4. The solid form of claim 3 , wherein the XRPD pattern further comprises peaks at 12.0, 12.2, and 13.9° 2θ±0.2° 2θ.
5. The solid form of claim 2 , which is characterized by an XRPD pattern that matches the XRPD pattern depicted in FIG. 1 .
6. The solid form of claim 2 , which exhibits an endothermic event, as characterized by DSC, with an onset temperature at about 265° C.±2° C. and/or a peak temperature at 267° C.±2° C.
7. The solid form of claim 2 , characterized by a DSC thermogram that matches the DSC thermogram depicted in FIG. 3 .
8. The solid form of claim 2 , which exhibits a weight increase of about 0.25% when subjected to an increase in relative humidity from about 0 to about 90% relative humidity.
9. The solid form of claim 2 , having approximately unit cell dimensions of: a=8.4 Å, b=8.4 Å, c=14.9 Å, α=90°, β=106°, and γ=90°.
10. The solid form of claim 1 , which comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 8.6, 14.0, and 20.8° 2θ±0.2° 2θ.
11. The solid form of claim 10 , which exhibits an endothermic event, as characterized by DSC, with an onset temperature at 96° C.±2° C.; and/or an exothermic event, as characterized by DSC, with an onset temperature at 169° C.±2° C.
12. The solid form of claim 1 , which comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 13.4, 19.5, and 20.9° 2θ±0.2° 2θ.
13. The solid form of claim 12 , which exhibits an exothermic event, as characterized by DSC, with an onset temperature at 168° C.±2° C.
14. The solid form of claim 1 , which comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 12.1, 12.7, and 18.4° 2θ±0.2° 2θ.
15. The solid form of claim 14 , which exhibits an endothermic event, as characterized by DSC, with an onset temperature at 135° C.±2° C.
16. The solid form of claim 1 , which comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.5, 10.8, and 21.9° 2θ±0.2° 2θ.
17. The solid form of claim 1 , which comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Ka radiation, comprising peaks at 8.6, 18.7, and 20.5° 2θ±0.2° 2θ.
18. The solid form of claim 17 , which exhibits an endothermic event, as characterized by DSC, with an onset temperature at 126° C.±2° C.
19. The solid form of claim 1 , which comprises a free base of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 12.5, 13.4, and 14.6° 2θ±0.2° 2θ.
20. The solid form of claim 19 , having approximately unit cell dimensions of: a=8.0 Å, b=14.8 Å, c=18.0 Å, α=90°, β=90°, and γ=90°.
21. The solid form of claim 1 , which comprises a besylate salt of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 15.0, 17.9 and 23.0° 2θ±0.2° 2θ.
22. The solid form of claim 21 , which exhibits an endothermic event, as characterized by DSC, with an onset temperature at 128° C.±2° C. and/or a peak temperature at 136° C.±2° C.
23. The solid form of claim 1 , which comprises a phosphate salt of a compound of formula (I), and is characterized by an XRPD pattern, when measured using Cu Kα radiation, comprising peaks at 10.8, 18.5, and 24.8° 2θ±0.2° 2θ.
24. A pharmaceutical composition comprising the solid form of claim 1 and a pharmaceutically acceptable excipient.
25. The solid form of claim 19 , wherein the XRPD pattern further comprises peaks at 20.9 and 22.8° 2θ±0.2° 2θ.
26. The solid form of claim 25 , wherein the XRPD pattern further comprises peals at 11.4 and 15.8° 2θ±0.2° 2θ.
27. The solid form of claim 19 , which is characterized by an XRPD pattern that matches the XRPD pattern depicted in FIG. 19 .
28. A pharmaceutical composition comprising the solid form of claim 2 and a pharmaceutically acceptable excipient.
29. A pharmaceutical composition comprising the solid form of claim 10 and a pharmaceutically acceptable excipient.
30. A pharmaceutical composition comprising the solid form of claim 12 and a pharmaceutically acceptable excipient.
31. A pharmaceutical composition comprising the solid form of claim 14 and a pharmaceutically acceptable excipient.
32. A pharmaceutical composition comprising the solid form of claim 16 and a pharmaceutically acceptable excipient.
33. A pharmaceutical composition comprising the solid form of claim 17 and a pharmaceutically acceptable excipient.
34. A pharmaceutical composition comprising the solid form of claim 19 and a pharmaceutically acceptable excipient.
35. A pharmaceutical composition comprising the solid form of claim 21 and a pharmaceutically acceptable excipient.
36. A pharmaceutical composition comprising the solid form of claim 23 and a pharmaceutically acceptable excipient.