Process for the manufacture of (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid
The present invention relates to a process for manufacturing (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid with the formula (Id) below and salts thereof The compound of formula (Id) is a prodrug of a catecholamine for use in treatment of neurodegenerative diseases and disorders such as Parkinson's Disease. The invention also relates to new intermediates of said process.
1. A potassium salt of the compound according to formula (A5-Y) below
wherein Y is K.
2. A process for preparation of compound (Id) with the formula below
from compound (I) with the formula below
comprising the following step
5) debenzylating compound (A5-Y) to obtain compound (Id) according to the reaction scheme below
wherein Y is selected from the group consisting of Li, Na and K, and
wherein said debenzylation is performed by hydrogenation in water.
3. The process according to claim 2 , wherein Y is K.
4. The process according to claim 2 , wherein said debenzylation is performed by hydrogenation in water in the presence of palladium on carbon (Pd/C) and hydrogen at about 2 bar.
5. The process according to claim 2 , wherein compound (Id) is isolated via filtration and neutralized with an acid.
6. The process according to claim 2 , wherein compound (Id) is isolated via filtration and neutralized with HCl, thereby affording compound (Id) as a heptahydrate.
7. The process according to claim 3 , wherein said debenzylation is performed by hydrogenation in water in the presence of palladium on carbon (Pd/C) and hydrogen at about 2 bar.
8. The process according to claim 3 , wherein compound (Id) is isolated via filtration and neutralized with an acid.
9. The process according to claim 3 , wherein compound (Id) is isolated via filtration and neutralized with HCl, thereby affording compound (Id) as a heptahydrate.
10. The process according to claim 4 , wherein compound (Id) is isolated via filtration and neutralized with an acid.
11. The process according to claim 4 , wherein compound (Id) is isolated via filtration and neutralized with HCl, thereby affording compound (Id) as a heptahydrate.
12. A process for preparation of the compound according to formula (A5-Y) below, comprising the following step
reacting compound (A4), or a salt thereof with alkali-hydroxide to obtain (A5-Y) according to the reaction scheme below
wherein Y is selected from Li, Na and K.
13. The process according to claim 12 wherein:
a) said alkali-hydroxide is lithium hydroxide and Y is Li; or
b) said alkali-hydroxide is sodium hydroxide and Y is Na; or
c) said alkali-hydroxide is potassium hydroxide and Y is K.
14. The process according to claim 12 , wherein said alkali-hydroxide is potassium hydroxide and Y is K.
15. The process according to claim 12 , wherein compound (A5-Y) is isolated by precipitation from an aqueous solution.
16. The process according to claim 14 , wherein compound (A4) is dissolved in THF, n-heptane and water.
17. The process according to claim 14 , further comprising a washing step.
18. The process according to claim 14 , further comprising a washing step using THF and n-heptane.
19. The process according to claim 16 , further comprising a step wherein THF is evaporated to precipitate compound (A5-Y), wherein Y is K.
20. The process according to claim 18 , further comprising a step wherein THF is evaporated to precipitate compound (A5-Y), wherein Y is K.
21. The process according to claim 3 , wherein said debenzylation is performed by hydrogenation in water in the presence of palladium on carbon (Pd/C) and hydrogen.
22. The process according to claim 21 , wherein compound (Id) is isolated via filtration and neutralized with an acid.
23. The process according to claim 21 , wherein compound (Id) is isolated via filtration and neutralized with an acid, thereby affording compound (Id) as a heptahydrate.