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-11827665-B2
Application number	US-202117385166-A
Country	US
Kind code	B2
Filing date	Jul 26, 2021
Priority date	May 20, 2019
Publication date	Nov 28, 2023
Grant date	Nov 28, 2023

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 pharmaceutically acceptable salts thereofThe 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 a new intermediate of said process.

First claim

The invention claimed is:

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

or a pharmaceutically acceptable salt thereof,
comprising deprotecting compound (A3) to obtain compound (Id), or a pharmaceutically acceptable salt thereof, according to the reaction scheme below:

2. The process of claim 1 , comprising deprotecting compound (A3) by contacting compound (A3) with a nucleophilic reagent to obtain compound (Id), or a pharmaceutically acceptable salt thereof.

3. The process according to claim 2 , further comprising the step of isolating compound (Id), or a pharmaceutically acceptable salt thereof.

4. The process according to claim 2 , wherein said nucleophilic reagent is selected from potassium hydroxide, potassium cyanide, and sodium hydroxide.

5. The process according to claim 2 , wherein said deprotection takes place in a mixture of methanol and water.

6. The process according to claim 2 , wherein compound (Id) is obtained as a potassium salt of compound (Id), and wherein potassium hydroxide or potassium cyanide is used as nucleophilic reagent.

7. The process according to claim 2 , wherein compound (Id) is obtained as a potassium salt of compound (Id), and wherein potassium hydroxide is used as nucleophilic reagent.

8. The process according to claim 2 , wherein compound (Id) is obtained as a sodium salt of compound (Id), and wherein sodium hydroxide is used as nucleophilic reagent.

9. The process according to claim 4 , wherein compound (Id) is obtained in a solution, and the process further comprises neutralizing the solution with a strong acid.

10. The process according to claim 9 , wherein the strong acid is HCl.

11. The process according to claim 2 , wherein compound (Id) is obtained as (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 heptahydrate.

12. The process according to claim 6 , further comprising formulating the potassium salt of compound (Id) into a solid oral dosage form.

13. The process according to claim 7 , further comprising formulating the potassium salt of compound (Id) into a solid oral dosage form.

14. The process according to claim 8 , further comprising formulating the sodium salt of compound (Id) into a solid oral dosage form.

15. The process according to claim 9 , further comprising formulating compound (Id), or a pharmaceutically acceptable salt thereof, into a solid oral dosage form.

16. The process according to claim 11 , further comprising formulating (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 heptahydrate compound (Id) into a solid oral dosage form.

17. The process according to claim 2 , wherein compound (A3) is prepared using the following step
reacting compound (A2) with (2S,3S,4S,5R,6R)-2-(methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate to obtain compound (A3) according to the reaction scheme below

wherein said reaction takes place in an aprotic solvent in the presence of a Lewis acid.

18. The process according to claim 17 , further comprising the step of isolating compound (A3).

19. The process according to claim 17 , wherein said aprotic solvent is dichloromethane or benzotrifluoride.

20. Previously presented 17 , The process according to claim 17 , wherein said aprotic solvent is dichloromethane, and said Lewis acid is boron trifluoride diethyl etherate.

21. The process according to claim 17 , wherein said aprotic solvent is benzotrifluoride, and said Lewis acid is boron trifluoride diethyl etherate.

Assignees

• H Lundbeck As

Inventors

• Juhl Martin
• Kværnø Lisbet
• Jacobsen Mikkel Fog

Classifications

• C07H15/26 Primary

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title

• C07H1/00 Primary

  Processes for the preparation of sugar derivatives · CPC title

• C07H15/02 Primary

  Acyclic radicals, not substituted by cyclic structures · CPC title

• C07H17/02 Primary

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

• A61P25/16

  Anti-Parkinson drugs · CPC title