Salts of obicetrapib and processes for their manufacture and intermediates thereof
Provided herein is a method for the manufacture of a compound of obicetrapib and salts thereof, such as calcium salts thereof. Also provided herein is amorphous obicetrapib hemicalcium. New intermediates for use in the synthesis of obicetrapib, and salts thereof are also provided, including obicetrapib HCl and a mesylate salt for the use in the synthesis of obicetrapib and amorphous obicetrapib hemicalcium.
1. Amorphous obicetrapib hemicalcium.
2. The amorphous obicetrapib hemicalcium of claim 1 , having an x-ray powder diffraction pattern comprising one or more peaks at about 3.4° 2θ, about 7.0° 2θ, and about 9.2° 2θ.
3. The amorphous obicetrapib hemicalcium of claim 1 , having a glass transition temperature at a value between about 109° C. and about 112° C., when measured by modulated differential scanning calorimetry in a sample pan with an opening.
4. The amorphous obicetrapib hemicalcium of claim 2 , having a glass transition temperature at a value between about 109° C. and about 112° ° C., when measured by modulated differential scanning calorimetry in a sample pan with an opening.
5. The amorphous obicetrapib hemicalcium of claim 1 , having a solid-state 13 C-NMR spectrum substantially the same as that of FIG. 17 .
6. The amorphous obicetrapib hemicalcium of claim 1 , having a solid-state 13 C-NMR spectrum where no peak is present at either about 22.1 ppm or about 29.5 ppm.
7. The amorphous obicetrapib hemicalcium of claim 2 , having a solid-state 13 C-NMR spectrum substantially the same as that of FIG. 17 .
8. The amorphous obicetrapib hemicalcium of claim 2 , having a solid-state 13 C-NMR spectrum where no peak is present at either about 22.1 ppm or about 29.5 ppm.
9. The amorphous obicetrapib hemicalcium of claim 3 , having a solid-state 13 C-NMR spectrum substantially the same as that of FIG. 17 .
10. The amorphous obicetrapib hemicalcium of claim 3 , having a solid-state 13 C-NMR spectrum where no peak is present at either about 22.1 ppm or about 29.5 ppm.
11. The amorphous obicetrapib hemicalcium of claim 4 , having a solid-state 13 C-NMR spectrum substantially the same as that of FIG. 17 .
12. The amorphous obicetrapib hemicalcium of claim 4 , having a solid-state 13 C-NMR spectrum where no peak is present at either about 22.1 ppm or about 29.5 ppm.
13. The amorphous obicetrapib hemicalcium of claim 1 , having a d90 particle size distribution of between 6 and 15 microns.
14. The amorphous obicetrapib hemicalcium of claim 2 , having a d90 particle size distribution of between 6 and 15 microns.
15. The amorphous obicetrapib hemicalcium of claim 3 , having a d90 particle size distribution of between 6 and 15 microns.
16. The amorphous obicetrapib hemicalcium of claim 4 , having a d90 particle size distribution of between 6 and 15 microns.
17. The amorphous obicetrapib hemicalcium of claim 1 , having a chemical purity of at least 99.0%.
18. The amorphous obicetrapib hemicalcium of claim 2 , having a chemical purity of at least 99.0%.
19. The amorphous obicetrapib hemicalcium of claim 17 , having a chemical purity of at least 99.9%.
20. The amorphous obicetrapib hemicalcium of claim 18 , having a chemical purity of at least 99.9%.
21. The amorphous obicetrapib hemicalcium of claim 1 , having an x-ray powder diffraction pattern substantially the same as that of FIG. 3 .
22. The amorphous obicetrapib hemicalcium of claim 1 , wherein the amorphous obicetrapib calcium does not birefringe.
23. The amorphous obicetrapib hemicalcium of claim 2 , wherein the amorphous obicetrapib calcium does not birefringe.
24. The amorphous obicetrapib hemicalcium of claim 3 , wherein the amorphous obicetrapib calcium does not birefringe.
25. The amorphous obicetrapib hemicalcium of claim 1 , wherein the obicetrapib hemicalcium is milled.
26. The amorphous obicetrapib hemicalcium of claim 1 , having a water content of less than about 4%.
27. The amorphous obicetrapib hemicalcium of claim 26 , having a water content of between about 0.5% and about 1.5%.