# US 2020/0369705 A1 · A 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

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- Number: US 2020/0369705 A1
- Document ID: US20200369705A1
- Status: Published application
- Kind: A1
- Application number: 16/876,843
- Filed: 2020-05-18
- Published: 2020-11-26
- Earliest claimed: 2019-05-20
- Assignees: H. Lundbeck A/S
- Applicants: H. Lundbeck A/S
- Inventors: Martin Juhl; Lisbet Kværnø; Mikkel Fog Jacobsen
- Web page: https://patentgrep.com/patent/US20200369705A1

## CPC

- C07H 15/02: Acyclic radicals, not substituted by cyclic structures
- C07H 15/26: Acyclic or carbocyclic radicals, substituted by hetero rings
- C07H 1/00: Processes for the preparation of sugar derivatives
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)

## 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]guinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid with the formula (Id) below and pharmaceutically acceptable 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 a new intermediate of said process.

## Claims

### Claim 1

A process for the preparation of compound (Id) with the formula below
or a pharmaceutically acceptable salt thereof
from compound (I), with the formula below
wherein said process comprises 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.

### Claim 2

A process for the manufacturing of compound (A3) below comprising 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.

### Claim 3 (depends on 1)

The process according to any of claim 1, wherein said aprotic solvent is dichloromethane or benzotrifluoride and said Lewis acid is boron trifluoride diethyl etherate.

### Claim 4

A compound of formula (A3) below
or a salt thereof.

### Claim 5

(canceled)

### Claim 6

A process for the preparation of compound (Id), or a pharmaceutically acceptable salt thereof with the formula below
from compound (I) with the formula below
wherein said process comprises the following step
deprotecting compound (A3) by contacting compound (A3) with a nucleophilic reagent to obtain compound (Id), or a pharmaceutically acceptable salt thereof according to the reaction scheme below

### Claim 7 (depends on 1)

The process according to any of claim 1, further comprising the following step
deprotecting compound (A3) by contacting compound (A3) with a nucleophilic reagent to obtain compound (Id), or a pharmaceutically acceptable salt thereof according to the reaction scheme below

### Claim 8 (depends on 7)

The process according to any of claim 7, wherein the nucleophilic reagent is selected from potassium hydroxide and sodium hydroxide.

### Claim 9 (depends on 7)

The process according to claim 7, wherein said deprotection takes place in a mixture of methanol and water.

### Claim 10 (depends on 1)

The process according to claim 1, wherein compound (A2) has been obtained by the following step
reacting compound (I), or a salt thereof with triisopropylsilyl chloride to obtain compound (A2) according to the reaction scheme below
wherein the reaction takes place in an aprotic solvent in the presence of a base.

### Claim 11 (depends on 10)

The process according to claim 10, wherein said aprotic solvent is dichloromethane and said base is N,N-diisopropylethylamine (DIPEA).

### Claim 12 (depends on 11)

The process according to claim 11, wherein said N,N-Diisopropylethylamine (DIPEA) is present in an amount of 4-5 equivalents relative to compound (I).

### Claim 13

(canceled)

### Claim 14

(canceled)

### Claim 15 (depends on 1)

The process according to claim 1, comprising an additional step of formulating compound (Id), or pharmaceutically acceptable salt thereof into a solid oral dosage form.