Processes for making a solid-state form of relugolix
The present invention is directed to processes for making an anhydrous form of relugolix, designated herein as Form T of anhydrous relugolix. The processes of making Form T of anhydrous relugolix are from the following: (i) Form A of the DMF solvate of relugolix; (ii) Form B of anhydrous relugolix; or (iii) amorphous relugolix.
1. A process for the preparation of Form T of anhydrous relugolix comprising:
a) forming a solution of Form A of the DMF solvate of relugolix in an alcohol at an elevated temperature; and
b) cooling the solution to yield Form T of anhydrous relugolix as a precipitate.
2. The process of claim 1 wherein the alcohol is methanol, ethanol, or isopropanol.
3. The process of claim 1 , wherein the elevated temperature is about 50-60° C.
4. The process of claim 1 , wherein the alcohol is heated to the elevated temperature to form the solution.
5. The process of claim 1 , wherein a mixture of Form A of the DMF solvate of relugolix and alcohol is heated to the elevated temperature to form the solution.
6. The process of claim 1 , wherein about 7-10 volumes of alcohol (mL) is used per weight (g) of Form A of the DMF solvate of relugolix.
7. The process of claim 1 , wherein the cooling is to about 17-24° C.
8. The process of claim 1 , wherein the solution is stirred while cooling.
9. The process of claim 1 , wherein the precipitate is filtered.
10. The process of claim 1 , wherein the precipitate is washed one or more times with an alcohol.
11. The process of claim 10 , wherein about 2-4 volumes (mL) of alcohol are used per weight (g) of Form A of the DMF solvate of relugolix.
12. The process of claim 10 , wherein the alcohol is methanol, ethanol, or isopropanol.
13. The process of claim 1 , wherein the precipitate is dried.
14. A process for the preparation of Form T of anhydrous relugolix comprising:
a) mixing amorphous relugolix or Form B of anhydrous relugolix with an alcohol to form a slurry; and
b) stirring the slurry to yield Form T of anhydrous relugolix.
15. The process of claim 14 , wherein the alcohol is methanol, ethanol, or an isopropanol/water mixture.
16. The process of claim 15 , wherein the ratio of isopropanol:water is about 19:1 (v/v).
17. The process of claim 14 , wherein about 10-15 volumes of alcohol (mL) is used per weight (g) of amorphous relugolix or Form B of anhydrous relugolix.
18. The process of claim 14 , wherein the stirring is for about 24-48 hours.
19. The process of claim 14 further comprising filtering the slurry of step b.
20. The process of claim 14 , wherein Form T of anhydrous relugolix is washed with an alcohol.
21. The process of claim 20 , wherein the alcohol is selected from methanol, ethanol and an isopropanol/water mixture.
22. The process of claim 20 , wherein about 2-4 volumes (mL) of alcohol are used for the wash per weight (g) of amorphous relugolix or Form B of anhydrous relugolix.