Claims for Patent: 12,448,366

Summary for Patent: 12,448,366

Title:	Solid forms of pralsetinib
Abstract:	The compound cis)-N-((S)-1-(6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl)ethyl)-1-methoxy-4-(4 methyl-6-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)cyclohexanecarboxamide can be prepared as a free base in various crystalline solid forms, and in various salt forms each having one or more solid forms.
Inventor(s):	Joshua Waetzig, Gordon D. Wilkie, Lauren MacEachern, Kimberly Jean Miller
Assignee:	Rigel Pharmaceuticals Inc
Application Number:	US18/000,168
Patent Claims:	1. A crystalline Solid Form A of the free base of (cis)-N-((S)-1-(6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl)ethyl)-1-methoxy-4-(4 methyl-6-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)cyclohexanecarboxamide. 2. The solid form of claim 1 characterized by an X-ray powder diffraction (XRPD) pattern having diffractions at angles (2 theta±0.2) of 5.0°, 9.7°, 12.7°, 13.6°, and 16.1°. 3. The solid form of claim 2, characterized by an X-ray Powder Diffraction (XRPD) pattern having additional diffractions at angles (2 theta±0.2) of 6.8, 19.2, 19.5, and 23.5. 4. The solid form of claim 1 characterized by an X-ray Powder Diffraction (XRPD) pattern having peaks at the same or substantially the same angles (2 theta±0.2) and corresponding d-spacing (A±0.2) of: 2-theta d-Spacing Relative (deg) (ang.) Intensity 4.95 17.82 62 6.80 12.98 16 9.74 9.07 29 12.71 6.96 48 13.62 6.50 100 14.82 5.97 9 16.06 5.52 39 17.18 5.16 5 17.83 4.97 8 19.22 4.62 20 19.52 4.54 35 20.50 4.33 5 21.56 4.12 6 23.09 3.85 14 23.51 3.78 16 24.77 3.59 5 25.59 3.48 10 25.97 3.43 9 27.86 3.20 7 29.41 3.03 7. 5. The solid form of claim 1, further characterized by one or more of: a differential scanning calorimetry (DSC) thermogram with an endothermic event observed at about 205° C.; and a reversible mass change of about 10% by DVS between 2-95% relative humidity. 6. A crystalline Solid Form B of the free base of (cis)-N-((S)-1-(6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl)ethyl)-1-methoxy-4-(4 methyl-6-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)cyclohexanecarboxamide. 7. The solid form of claim 6, characterized by an X-ray powder diffraction (XRPD) pattern having diffractions at angles (2 theta±0.2) of 5.9°, 8.8°, 11.6°, 14.7°, and 19.5°. 8. The solid form of claim 7, characterized by an X-ray Powder Diffraction (XRPD) pattern having additional diffractions at angles (2 theta±0.2) of 17.0, 17.6 and 22.2. 9. The solid form of claim 6, characterized by an X-ray Powder Diffraction (XRPD) pattern having peaks at the same or substantially the same angles (2 theta±0.2) and corresponding d-spacing (A±0.2) of: 2-theta d-Spacing Relative (deg) (ang.) Intensity 5.89 14.99 100 8.81 10.03 28 11.58 7.64 33 14.73 6.01 23 17.01 5.21 11 17.63 5.03 8 19.45 4.56 13 22.21 4.00 5. 10. The solid form of claim 6, further characterized by one or more of: a differential scanning calorimetry (DSC) thermogram with an endothermic event observed at about 205° C.; and a reversible mass change of about 10% by DVS between 2-95% relative humidity. 11. A crystalline Solid Form C of the free base of (cis)-N-((S)-1-(6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl)ethyl)-1-methoxy-4-(4 methyl-6-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)cyclohexanecarboxamide. 12. A Solid Form 5-A of crystalline hydrochloride salt of pralsetinib. 13. A Solid Form 5-B of crystalline hydrochloride salt of pralsetinib. 14. The solid form of claim 13 characterized by one or more of the following: a XRPD pattern comprising characteristic diffraction peaks at 2-theta angles at approximately (±0.2 degrees) 6.1°, 8.9, 9.5°, 15.0°, 16.6°; and A TGA/DSC thermogram characterized by an initial mass loss of 3.4 wt. % associated with a broad endotherm with an onset of 88.7° C. (±0.2 degrees) and a second mass loss event of 6.7 wt. % was observed from the end of the first broad endotherm to the end of the melt which had an onset of 244.2° C. (±0.2 degrees. 15. A Solid Form 5-C of crystalline hydrochloride salt of pralsetinib. 16. The solid form of claim 15 characterized by XRPD pattern 5-C. 17. The solid form of claim 11, characterized by an X-ray powder diffraction (XRPD) pattern having diffractions at angles (2 theta±0.2) of 5.8°, 8.7°, 11.0°, 13.6°, and 20.2°. 18. The solid form of claim 12 characterized by a XRPD pattern having diffractions at angles (2 theta±0.2) of 5.0°, 6.1°, 91°, 9.9°, and 14.7°. 19. The solid form of claim 15 characterized by a XRPD pattern having diffractions at angles (2 theta±0.2) of 6.4°, 8.5°, 8.9°, 9.6°, and 17.3°.