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]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.
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.
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.
3. 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.
4. A compound of formula (A3) below
or a salt thereof.
5. 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
6. The process according to 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
7. The process according to claim 6 , wherein the nucleophilic reagent is selected from potassium hydroxide and sodium hydroxide.
8. The process according to claim 6 , wherein said deprotection takes place in a mixture of methanol and water.
9. 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.
10. The process according to claim 9 , wherein said aprotic solvent is dichloromethane and said base is N,N-diisopropylethylamine (DIPEA).
11. The process according to claim 10 , wherein said N,N-Diisopropylethylamine (DIPEA) is present in an amount of 4-5 equivalents relative to compound (I).
12. 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.