Method for preparing ropinirole

A compound and reaction technology, applied in the field of preparation of ropinirole hydrochloride, can solve the problems of weak positioning, unsuitable for industrial production, difficult to purify and the like

Inactive Publication Date: 2007-05-09
2Y CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The raw materials of this method are not easy to obtain, and the positioning is not strong during cyclization, resulting in a large amount of isomers, which is not easy to purify, and is not suitable for industrial production

Method used

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  • Method for preparing ropinirole
  • Method for preparing ropinirole
  • Method for preparing ropinirole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1 3-nitro-4-chlorophenylacetic acid

[0054] Completely dissolve 68.2 g of 4-chlorobenzoic acid into 800 mL of concentrated sulfuric acid, add 20 mL of fuming nitric acid at 0°C, and then stir for 1 hour. After the reaction was completed, the reaction solution was slowly poured into 1000 mL of ice water, stirred for 30 minutes, and then filtered. The filter cake was stirred with 2000 mL of ice water in the reaction kettle for 30 minutes, then filtered, washed with ice water until neutral, and then vacuum-dried at 50°C to obtain 75.14 g of the title compound as a light yellow solid, with a yield of 88.7%. 1 HNMR (300MHz, DMSO-d6): 7.82 (d, J = 2.7, 1H), 7.52 (d, J = 8.1, 1H), 7.44 (dd, J = 8.1, 2.7, 1H), 3.72 (s, 2H) .

Embodiment 2

[0055] Example 2 N, N-dipropyl-3-nitro-4-chlorophenylacetamide

[0056] 21.3 grams of 3-nitro-4-chlorophenylacetic acid and 200 mL of SOCl2 were added into a 500 mL reaction flask, and the reaction was refluxed for 2.5 hours. After the reaction, SOCl2 was recovered to obtain light brown oil.

[0057]Add 100 mL of ethyl acetate to the oily substance, dissolve it and drop it into the ethyl acetate solution containing 27.3 mL of dipropylamine at room temperature, white smoke will be produced when the dropwise addition starts. After the addition was complete, stir at room temperature for 3 hours. Then add 100 mL of 5% NaOH solution to wash, then wash with 100 mL of 10% hydrochloric acid, and separate the organic layer. The solvent was recovered to obtain the title compound as a light brown oil, with a yield of 84.8% and a purity of 96.4%. The oil was used directly in the next step.

Embodiment 3

[0058] Example 3 N, N-dipropyl-3-nitro-4-chlorophenethylamine

[0059] Dissolve 15 g of N,N-dipropyl-3-nitro-4-chlorophenylacetamide in 100 mL of THF, and then add 5 g of LiAlH4 in batches at room temperature. React overnight at room temperature. 15mL of ice water was added dropwise, and a large amount of gas was released at the beginning. After the addition, the solution became a paste and was filtered. The organic phase was dried over anhydrous MgSO4 and the solvent was evaporated to give 14.3 g of the title compound in an almost quantitative yield with a purity of 96.1%. 1 HNMR (400MHz, DMSO-d6): 7.93 (1H, d, J = 2.4Hz), 7.68 (1H, d, J = 8.4Hz), 7.54 (1H, dd, J 1 =8.4Hz,J 2 =2.4Hz), 3.82(2H, s), 3.26(2H, m), 3.18(2H, m), 1.52(2H, m), 1.44(2H, m), 0.854(3H, t, J=7.3Hz ), 0.776 (3H, t, J = 7.6 Hz).

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Abstract

This invention adopts commercially available phenylacetic acid or 4-substituted phenylacetic acid as the starting material, and comprises nitrifying, reacting into acyl chloride and amide, reducing amide, reducing nitryl, condensing, cyclizating, reducing carbanyl and dehalogenating to obtain ropinirole.

Description

field of invention [0001] The present invention relates to ropinirole, especially the preparation method of ropinirole hydrochloride. Background technique [0002] Ropinirole hydrochloride was developed by Smithkline Beecham and first launched in the UK in 1996 for the treatment of Parkinson's disease. Soon, France and the United States were also allowed to market. The product name is ReQuip, and the synonym is SKF101468. Ropinirole is a selective non-ergoline dopamine D2 receptor agonist. Unlike other dopamine agonists, this product has a simple chemical structure similar to natural dopamine. It is useful for the treatment of early Parkinson's disease and as an adjuvant drug for levodopa treatment. Effective. [0003] So far, the synthetic routes reported in the literature can be divided into three types according to different types of starting materials. The first kind of method is that patent US4452808 (1984) and Journal of Medicinal Chemistry, 1985,28 (10), 1533-6; 1...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/34A61K31/404A61P25/16
Inventor 何训贵刘传军周志辉王元
Owner 2Y CHEM
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