Compounds and synthetic methods for the preparation of retinoid X receptor-specific retinoids
Provided herein are compounds useful for the preparation of compounds that have retinoid-like biological activity. Also provided herein are processes for the preparation of compounds that have retinoid-like biological activity.
1. A method of making Compound 38,
or a pharmaceutically acceptable salt thereof,
comprising a synthetic process of preparing intermediate compound 8, (Z)-3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)but-2-en-1-ol, of Formula (XII),
or a solvate thereof,
by reacting compound 4, sodium (5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)boronate of Formula (XVI),
or a solvate thereof,
with compound 7, (Z)-3-iodobut-2-en-1-ol, of Formula (XVII),
or a solvate thereof,
in the presence of Pd/C and a base, such that the compound of Formula (XII) or a solvate thereof is prepared.
2. The method of claim 1 , wherein Compound 38 has an enantiomeric excess of Compound A,
of at east about 98.0%.
3. The method of claim 1 , wherein the base is K 2 CO 3 .
4. The method of claim 1 , wherein the reaction comprises a solvent comprising EtOH.
5. A method of synthesizing compound 8, (Z)-3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)but-2-en-1-ol, of Formula (XII),
or a solvate thereof,
by reacting compound 4, sodium (5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)boronate of Formula (XVI),
or a solvate thereof,
with compound 7, (Z)-3-iodobut-2-en-1-ol, of Formula (XVII),
or a solvate thereof,
in the presence of Pd/C and a base, such that the compound of Formula (XII) or a solvate thereof is prepared.
6. The method of claim 5 , wherein the base is K 2 CO 3 .
7. The method of claim 5 , wherein the reaction comprises a solvent comprising EtOH.
8. The method of claim 1 , wherein the synthetic process of preparing intermediate compound 8 is carried out at kilogram scale.
9. The method of claim 1 , wherein the synthetic process of preparing intermediate compound 8 is carried out utilizing at least 1 kilogram of each of compound 4 and compound 7.
10. The method of claim 1 , wherein the synthetic process of preparing intermediate compound 8 produces at least 1 kilogram of compound 8.
11. The method of claim 1 , wherein the synthetic process of preparing intermediate compound 8 has a yield of about 84%.
12. The method of claim 1 , wherein the synthetic process of preparing intermediate compound 8 has a yield of at least 84%.
13. The method of claim 5 , wherein synthesizing compound 8 is carried out at kilogram scale.
14. The method of claim 5 , wherein synthesizing compound 8 is carried out utilizing at least 1 kilogram of each of compound 4 and compound 7.
15. The method of claim 5 , wherein synthesizing compound 8 produces at least 1 kilogram of compound 8.
16. The method of claim 5 , wherein synthesizing compound 8 has a yield of about 84%.
17. The method of claim 5 , wherein synthesizing compound 8 has a yield of at least 84%.