IP Library › Granted Patent US 12,398,169
Granted Patent B2
US 12,398,169 · App. 18/507,662 · Granted Aug 26, 2025

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

Inventors: Martin Juhl (Valby, DK); Frans Dennis Therkelsen (Valby, DK); Tobias Gylling Frihed (Valby, DK)
Assignee: H. Lundbeck A/S
C07H15/26C07H1/00
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Quick Facts
Patent No.
US 12,398,169
App. No.
18/507,662
Granted
Aug 26, 2025
Kind
B2
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.

Claims (37)

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.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 25, 2024
From: JUHL, MARTIN; FRIHED, TOBIAS GYLLING; THERKELSEN, FRANS DENNIS
To: H. LUNDBECK A/S
Reel/Frame 066247/0516 →
Priority Claims (2)
DK PA201900599 · May 20, 2019 · national
DK PA201900636 · May 24, 2019 · national
Continuity (3)
Continuation 17391439 · Aug 2, 2021
Continuation 16876878 · May 18, 2020
Related Publication 20240352055A1 · Oct 24, 2024
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