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Method for preparing rotigotine and derivative thereof

A compound and a selected technology, applied in the directions of organic chemistry methods, chemical instruments and methods, separation of optically active compounds, etc., can solve the problems of low yield, difficulty in industrial production, expensive preparation of rotigotine, etc., and achieve easy operation. , good social and economic benefits, low cost effect

Inactive Publication Date: 2010-06-02
苏州凯达生物医药技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] The purpose of the present invention is to provide a new method for preparing rotigotine and its derivatives, which solves the problems in the prior art that the preparation cost of rotigotine is high, industrial production is difficult, and the yield is low and difficult to purify.

Method used

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  • Method for preparing rotigotine and derivative thereof
  • Method for preparing rotigotine and derivative thereof
  • Method for preparing rotigotine and derivative thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] The preparation of embodiment 1 rotigotine

[0055] Preparation of 2-(N-n-propylamino)-5-methoxytetralin

[0056] 5-Methoxy-2-tetralone (3.52 g, 20 mmol) and propylamine (3.3 mL, 40 mmol) were dissolved in 50 mL of absolute ethanol, and a catalytic amount of p-toluenesulfonic acid was added , heated to reflux and stirred for 2 to 5 hours; the reaction mixture was cooled to 0°C, under stirring, slowly added sodium borohydride (1.14 g, 30 mmol), then slowly warmed up to 30°C, and continued to stir at this temperature 24 hours. Remove the organic solvent, add 100 ml of 10% sodium hydroxide solution, stir for 1 hour, and then extract with 100 ml of dichloromethane for three consecutive extractions. The organic solvent was dried over anhydrous sodium sulfate, filtered, and the solvent was extracted to obtain 3.2 g (62%) of an oil.

[0057] Preparation of Chiral Organic Phosphonic Acids

[0058] Slowly add 1 equivalent of potassium hydroxide ethanol solution dropwise to 1...

Embodiment 2

[0070] The preparation of embodiment 2 rotigotine hydrochloride

[0071] Preparation of 2-(N-n-propylamino)-5-methoxytetralin

[0072] 5-methoxy-2-tetralone (3.52 g, 20 mmol) and propylamine (3.3 ml, 40 mmol) were dissolved in 50 ml of absolute ethanol, then a catalytic amount of camphorsulfonic acid was added, heated to reflux Stir for 2-5 hours; cool the reaction mixture to room temperature, add a catalytic amount of palladium carbon catalyst, add potassium borohydride and continue stirring at room temperature for 24 hours. Suction filtration was performed to remove palladium carbon, washed with 50 ml of dichloromethane, the organic liquid was combined and concentrated to obtain 3.3 g of oil.

[0073] Preparation of Chiral Organic Phosphonic Acids

[0074] Mix 1 equivalent of o-chlorobenzaldehyde and 2.5 equivalents of isobutyraldehyde evenly, control the temperature, slowly add 1 equivalent of potassium hydroxide ethanol solution dropwise, then react overnight at 60-65°C,...

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Abstract

The invention discloses a method for preparing a compound of a formula (I) or pharmaceutically acceptable salts thereof. The method is characterized by comprising the following steps of: (1) using a compound of a formula (II) as a raw material and carrying out a reduction and amination reaction with an appropriate reducing agent to obtain a compound of a formula (III); (2) using 2-quinary heterocyclic substituted ethanol as a raw material and reacting to obtain a compound of a formula (IV) under the conditions of appropriate reagent, temperature and solvent; (3) after carrying out chiral separation on the compound of the formula (III), carrying out a condensation reaction with the compound of the formula (I) under an alkaline condition to obtain a compound of a formula (V); and (4) carrying out demethylation protection on the compound of the formula (V) under the condition of appropriate temperature and solvent to obtain the compound of the formula (I), wherein R1 in each formula is selected from C1-8 alkyl groups or aromatic bases which can be arbitrarily substituted, X is selected from halogen atoms or p-toluenesulfonic acid groups and methanesulfonic acid groups for protecting alcoholic extract hydroxyl groups, and Y is selected from O, S and N. A target product obtained by the method has high optical purity, convenient operation, lower cost, higher yield and less pollution and is suitable for industrialized production.

Description

technical field [0001] The invention belongs to the technical field of pharmacy, and in particular relates to a method for preparing rotigotine and derivatives thereof. Background technique [0002] Parkinson's disease (PD), also known as Parkinson's paralysis, is the most common degenerative disease of the central nervous system in middle-aged and elderly people. Tremor refers to shaking and shaking of the head and limbs, and paralysis refers to the inability to move a part or all of the limbs voluntarily. Typical symptoms include movement disturbances, tremors, and muscle stiffness. Generally, the onset begins at the age of 50-65, and the incidence rate increases gradually with age. The incidence rate at the age of 60 is about 1‰, and the incidence rate at the age of 70 reaches 3‰-5‰. There are currently more than 1.7 million people in my country suffering from this disease. disease. Current data show that the incidence of Parkinson's disease is slightly higher in males ...

Claims

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Application Information

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IPC IPC(8): C07D333/20C07B57/00
Inventor 陆军张燕飞杨进茅冬燕沈宗旋
Owner 苏州凯达生物医药技术有限公司
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