Synthetic methods for preparation of 4-(2-chloro-4-methoxy-5-methylphenyl)-n-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-n-prop-2-ynyl-1,3-thiazol-2-amine
The present disclosure relates to the fields of chemistry and medicine, more particularly to processes for making 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-prop-2-ynyl-1,3-thi-azol-2-amine (Compound 1), pharmaceutically acceptable salts, and crystalline forms thereof, for the treatment of congenital adrenal hyperplasia (CAH).
1. A compound that is 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-prop-2-ynyl-1,3-thiazol-2-amine (Compound 1):
wherein the enantiomeric excess (e.e.%) of the compound is at least 99.7%.
2. The compound according to claim 1 , wherein the enantiomeric excess (e.e.%) of Compound 1 is at least 99.8%.
3. The compound according to claim 1 , wherein the enantiomeric excess (e.e.%) of Compound 1 is at least 99.9%.
4. A method of treating congenital adrenal hyperplasia (CAH), in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to claim 1 .
5. The method according to claim 4 , wherein the enantiomeric excess (e.e.%) of Compound 1 is at least 99.8%.
6. The method according to claim 4 , wherein the enantiomeric excess (e.e.%) of Compound 1 is at least 99.9%.
7. The method according to claim 4 , wherein the congenital adrenal hyperplasia is classic congenital adrenal hyperplasia.
8. The method according to claim 4 , wherein the method further comprises administering to the subject a glucocorticoid.
9. The method according to claim 7 , wherein the method further comprises administering to the subject a glucocorticoid.
10. A pharmaceutically acceptable salt of 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl) ethyl]-5-methyl-N-prop-2-ynyl-1,3-thiazol-2-amine (Compound 1):
wherein the enantiomeric excess (e.e. %) of Compound 1 is at least 99.7%.
11. The salt according to claim 10 , wherein the enantiomeric excess (e.e. %) of Compound 1 is at least 99.8%.
12. The salt according to claim 10 , wherein the enantiomeric excess (e.e. %) of Compound 1 is at least 99.9%.
13. A method of treating congenital adrenal hyperplasia (CAH), in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of Compound 1 according to claim 10 .
14. The method according to claim 13 , wherein the enantiomeric excess (e.e. %) of Compound 1 is at least 99.8%.
15. The method according to claim 13 , wherein the enantiomeric excess (e.e. %) of Compound 1 is at least 99.9%.
16. The method according to claim 13 , wherein the congenital adrenal hyperplasia is classic congenital adrenal hyperplasia.
17. The method according to claim 13 , wherein the method further comprises administering to the subject a glucocorticoid.
18. The method according to claim 16 , wherein the method further comprises administering to the subject a glucocorticoid.