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

Patent metadata

Field	Value
Publication number	US-12398169-B2
Application number	US-202318507662-A
Country	US
Kind code	B2
Filing date	Nov 13, 2023
Priority date	May 20, 2019
Publication date	Aug 26, 2025
Grant date	Aug 26, 2025

Abstract

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.

First claim

The invention claimed is:

1. A process for preparation of compound (Id) with the formula below

comprising the following step
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.

2. The process according to claim 1 , wherein Y is K.

3. The process according to claim 1 , wherein said debenzylation is performed by hydrogenation in water in the presence of palladium on carbon (Pd/C) and hydrogen.

4. The process according to claim 1 , 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 1 , wherein compound (Id) is isolated via filtration and neutralized with an acid.

6. The process according to claim 1 , wherein compound (Id) is isolated via filtration and neutralized with an acid, thereby affording compound (Id) as a heptahydrate.

7. The process according to claim 1 , wherein compound (Id) is isolated via filtration and neutralized with HCl, thereby affording compound (Id) as a heptahydrate.

8. 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.

9. 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.

10. The process according to claim 2 , wherein compound (Id) is isolated via filtration and neutralized with an acid.

11. The process according to claim 2 , wherein compound (Id) is isolated via filtration and neutralized with an acid, thereby affording compound (Id) as a heptahydrate.

12. The process according to claim 2 , wherein compound (Id) is isolated via filtration and neutralized with HCl, thereby affording compound (Id) as a heptahydrate.

13. The process according to claim 3 , wherein compound (Id) is isolated via filtration and neutralized with an acid.

14. The process according to claim 3 , wherein compound (Id) is isolated via filtration and neutralized with an acid, thereby affording compound (Id) as a heptahydrate.

15. The process according to claim 3 , wherein compound (Id) is isolated via filtration and neutralized with HCl, thereby affording compound (Id) as a heptahydrate.

16. The process according to claim 4 , wherein compound (Id) is isolated via filtration and neutralized with an acid.

17. The process according to claim 4 , wherein compound (Id) is isolated via filtration and neutralized with an acid, thereby affording compound (Id) as a heptahydrate.

18. The process according to claim 4 , wherein compound (Id) is isolated via filtration and neutralized with HCl, thereby affording compound (Id) as a heptahydrate.

19. The process according to claim 1 , further comprising the following step
reacting compound (A4), or a salt thereof, with alkali-hydroxide to obtain the compound (A5-Y) according to the reaction scheme below

wherein Y is selected from the group consisting of Li, Na and K.

20. The process according to claim 19 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.

21. The process according to claim 19 , wherein said alkali-hydroxide is potassium hydroxide and Y is K.

22. The process according to claim 19 , wherein compound (A5-Y) is isolated by precipitation from an aqueous solution.

23. The process according to claim 19 , wherein compound (A4) is dissolved in THF, n-heptane and water.

24. The process according to claim 23 , wherein said alkali-hydroxide is potassium hydroxide and Y is K.

25. The process according to claim 23 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.

Assignees

• H Lundbeck As

Inventors

• Juhl Martin
• Therkelsen Frans Dennis
• Frihed Tobias Gylling

Classifications

• C07B2200/07

  Optical isomers · CPC title

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07H17/02 Primary

  Heterocyclic radicals containing only nitrogen as ring hetero atoms · CPC title

• C07D221/08 Primary

  Aza-anthracenes · CPC title

• C07D221/06

  Ring systems of three rings · CPC title