Synthesis of nirogacestat
The present disclosures are directed to processes for synthesizing (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide (“nirogacestat”).
1. A pharmaceutical composition comprising:
(1) 98.0% to 99.9% of nirogacestat, or a pharmaceutically acceptable salt thereof; and
(2) 0.6% to 0.01% of Compound 2
or a pharmaceutically acceptable salt thereof,
wherein the composition is substantially free of Compound 13
2. The composition of claim 1 , wherein the nirogacestat, or a pharmaceutically acceptable salt thereof, is present in an amount of about 1 mg to about 200 mg.
3. The composition of claim 1 , wherein the nirogacestat, or a pharmaceutically acceptable salt thereof, is present in an amount of about 1 mg to about 150 mg.
4. The composition of claim 1 , wherein the nirogacestat, or a pharmaceutically acceptable salt thereof, is present in an amount of about 1 mg to about 100 mg.
5. The composition of claim 1 , wherein the nirogacestat, or a pharmaceutically acceptable salt thereof, is present in an amount of about 1 mg to about 75 mg.
6. The composition of claim 1 , wherein the nirogacestat, or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg to about 60 mg.
7. A pharmaceutical composition comprising:
(1) 98.0% to 99.9% of nirogacestat, or a pharmaceutically acceptable salt thereof; and
(2) 0.3% to 0.01% of Compound 3
or a pharmaceutically acceptable salt thereof,
wherein the composition is substantially free of Compound 13
8. A pharmaceutical composition comprising:
(1) 98.0% to 99.9% of nirogacestat, or a pharmaceutically acceptable salt thereof; and
(2) 0.5% to 0.01% of Compound 4
or a pharmaceutically acceptable salt thereof,
wherein the composition is substantially free of Compound 13
9. A pharmaceutical composition comprising:
(1) 98.0% to 99.9% of nirogacestat, or a pharmaceutically acceptable salt thereof; and
(2) 0.5% to 0.01% of Compound 5
or a pharmaceutically acceptable salt thereof,
wherein the composition is substantially free of Compound 13
10. A pharmaceutical composition comprising:
(1) 98.0% to 99.9% of nirogacestat, or a pharmaceutically acceptable salt thereof; and
(2) 0.5% to 0.01% of Compound 6
or a pharmaceutically acceptable salt thereof,
wherein the composition is substantially free of Compound 13
11. A pharmaceutical composition comprising:
(1) 98.0% to 99.9% of nirogacestat, or a pharmaceutically acceptable salt thereof; and
(2) 0.5% to 0.01% of Compound 7
or a pharmaceutically acceptable salt thereof,
wherein the composition is substantially free of Compound 13
12. A pharmaceutical composition comprising:
(1) 98.0% to 99.9% of nirogacestat, or a pharmaceutically acceptable salt thereof; and
(2) 0.5% to 0.01% of Compound 8
or a pharmaceutically acceptable salt thereof,
wherein the composition is substantially free of Compound 13
13. A pharmaceutical composition comprising:
(1) 98.0% to 99.9% of nirogacestat, or a pharmaceutically acceptable salt thereof; and
(2) 0.05% to 0.005% of imidazole, or a pharmaceutically acceptable salt thereof, wherein the composition is substantially free of Compound 13