Method for synthesizing (R)-5-(2-amino propyl)-2-methoxybenzenesulfonamide

A kind of technology of methoxybenzenesulfonamide and synthetic method, applied in the synthesis field of -5--2-methoxybenzenesulfonamide, can solve problems such as long route, high price, unavoidable by-products, etc., achieve simplified purification The method, the price is cheap, and the effect is conducive to industrial production

Inactive Publication Date: 2009-06-24
SHANGHAI BAILING PHARMA TECH CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this method inevitably has by-products in the ortho and meta positions, and because after the Friedel-Crafts reaction, the carbonyl of the carboxylic acid is converted into a ketone carbonyl, and the acidity of the carbon in the or...

Method used

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  • Method for synthesizing (R)-5-(2-amino propyl)-2-methoxybenzenesulfonamide
  • Method for synthesizing (R)-5-(2-amino propyl)-2-methoxybenzenesulfonamide

Examples

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Embodiment 1

[0032] In a 500ml dry four-necked bottle, add 250ml of anhydrous tetrahydrofuran and 12g of magnesium powder, dropwise add 1ml of dibromoethane, add dropwise 70g of p-methoxychlorobenzene after triggering, control the dropping speed, make the reaction solution slightly reflux, and complete the addition , heating to reflux until the magnesium powder disappears. Cool to 0-5 degrees, add 29g of chiral propylene oxide dropwise, add saturated ammonium chloride aqueous solution to extract the reaction after adding and stir for 2 hours, concentrate THF, extract with ethyl acetate, perform conventional post-treatment, and the obtained product can be used directly react in the next step.

[0033] Dissolve the product from the previous step in 300ml of dichloromethane, add 100ml of triethylamine and 100g of p-toluenesulfonyl chloride, react overnight at room temperature, concentrate, add water and ethyl acetate for extraction, and obtain 120g of a white solid after conventional post-tre...

Embodiment 2

[0038] In a 1000ml dry four-neck flask, add 500ml of anhydrous tetrahydrofuran and 24g of magnesium powder, dropwise add 1ml of dibromoethane, add dropwise 187g of p-methoxybromobenzene after triggering, control the dropping speed, make the reaction solution slightly reflux, and complete the addition , heating to reflux until the magnesium powder disappears. Cool to 0-5 degrees, add 60g of chiral propylene oxide dropwise, add saturated ammonium chloride aqueous solution to extract the reaction after adding and stir for 2 hours, concentrate THF, extract with ethyl acetate, and perform conventional post-treatment. The obtained product can be used directly react in the next step.

[0039] Dissolve the product from the previous step in 600ml of dichloromethane, add 200ml of triethylamine and 200g of p-toluenesulfonyl chloride, react overnight at room temperature, concentrate, add water and ethyl acetate for extraction, and obtain 250g of a white solid after conventional post-treat...

Embodiment 3

[0044] In a 500ml dry four-necked bottle, add 250ml of anhydrous tetrahydrofuran and 12g of magnesium powder, dropwise add 1ml of dibromoethane, add dropwise 70g of p-methoxychlorobenzene after triggering, control the dropping speed, make the reaction solution slightly reflux, and complete the addition , heating to reflux until the magnesium powder disappears. Cool to 0-5 degrees, add 47g of chiral epichlorohydrin dropwise, add saturated ammonium chloride aqueous solution to extract the reaction after adding and stir for 2 hours, concentrate THF, extract with ethyl acetate, and perform conventional post-treatment, the obtained product dissolves In methanol, add 20 g of palladium carbon, hydrogenate at normal pressure, filter after the reaction, concentrate to dryness and directly use in the next reaction.

[0045] Dissolve the product from the previous step in 300ml of dichloromethane, add 100ml of triethylamine and 100g of p-toluenesulfonyl chloride, react overnight at room tem...

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Abstract

The invention relates to a method for synthesizing (R)-5-(2-aminopropyl)-2-methoxyl benzsulfamide. In the method, dihalogen anisole is used as initial raw material to react with metal. The reaction for opening ring of chiral propylene oxide or chiral epoxy chloropropane is the key reaction. Newly generated hydroxide radical reacts with substituted benzene sulfone chloride or methylsulfonyl chloride to generate leaving group to be ammonolyzed or azided and hydrolyzed or reduced into amine. (R)-5-(2-aminopropyl)-2-methoxyl benzsulfamide is prepared by protecting amido, benzene ring sulfonation, acylatation, aminolysis and deamination protection.

Description

Technical field: [0001] The invention relates to the field of synthesis of pharmaceutical compounds, in particular to a synthesis method of (R)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide. Background technique: [0002] Tamsulosin hydrochloride (I) is a pharmaceutically active substance of an alpha-adrenergic receptor antagonist, and is mainly used for the treatment of prostate dysfunction. Its chemical name is (R)-5-(2-((2-(2-ethoxyphenoxy)ethyl)amino)-2-methoxybenzenesulfonamide, which belongs to benzenesulfonamide and sulfamoyl Substances of the phenethylamine group. [0003] [0004] (R)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide (II) is a key intermediate in the synthesis of tamsulosin hydrochloride. The following methods have been reported: [0005] US 5447958 uses (-)-2-(p-methoxyphenyl)-1-methylethylamine as the starting material to synthesize II, but does not disclose its synthesis. [0006] EP 380144 reductive amination of 5-acetonyl-2-methoxybenzenesul...

Claims

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Application Information

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IPC IPC(8): C07C311/37C07C303/40
Inventor 沈鑫廖立新林复兴何晓杨继东詹华杏
Owner SHANGHAI BAILING PHARMA TECH CO LTD
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