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Preparation method of 3-(2-aminoethyl)-N-methyl-1H-indole-5-methanesulfonamide

A technology of methylbenzenemethanesulfonamide and nitrobenzenemethanesulfonamide, which is applied in the field of preparation of pharmaceutical intermediates, can solve the problems of harsh reaction conditions, high production costs, and high prices, and achieve easy control of reaction conditions and low production costs , the effect of fewer reaction steps

Active Publication Date: 2012-05-02
SHANDONG XINHUA PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] There are many shortcomings in the above methods, wherein the method (1) is catalyzed by PdO / C for reduction, but due to the high price, easy poisoning and deactivation, difficult regeneration, high requirements for raw material purity, large consumption, high production cost, and many three wastes, Mother liquor is difficult to recycle, and 4-amino-N-methylbenzenesulfonamide hydrochloride is unstable in the air, easy to oxidize and deteriorate, and the yield is also low
Although method (2) is similar to the present invention, it increases the protective group and prolongs the synthetic route, which not only increases the use of raw materials, the yield is also low, and what generates is different compounds
The above methods are complex in operation, harsh in reaction conditions, poor in product quality, low in yield, high in three wastes, high in production cost, and do not conform to industrialized production.

Method used

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  • Preparation method of 3-(2-aminoethyl)-N-methyl-1H-indole-5-methanesulfonamide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Step A: add 95% ethanol 80kg in the 200L autoclave that stirrer, thermometer are equipped with, 12kg p-nitro-N-methylbenzenesulfonamide and 2kg water-containing 10% active nickel, ventilate, be warming up to under stirring 85°C, feed hydrogen pressure to 0.6Mpa, and react for 2 hours. Remove the catalyst by pressure filtration, pour the filter pressure into a 200L glass-lined reactor to cool down to room temperature, adjust the solution to clarification with dilute hydrochloric acid under stirring, cool down to -5°C with ice-salt water, and dropwise add 12kg of 30% Sodium nitrite aqueous solution, drop in about 15 minutes (PH should be below 1), take a small amount of reaction solution on the drop plate to measure the end point, so that the starch potassium iodide test solution turns blue. Continue stirring for 10 minutes to retest the endpoint. Add 28.7 kg of aqueous solution made of 2.8 kg of sodium hydrosulfite and 2.5 kg of sodium hydroxide under cooling, keep the ...

Embodiment 2

[0034]Step A: Add 80kg of 95% ethanol, 12kg of p-nitro-N-methylbenzenesulfonamide and 1.3kg of active nickel containing 10% water in a 200L high-pressure reactor equipped with a stirrer and a thermometer, ventilate, and heat up under stirring to 95°C, and the pressure of hydrogen gas was introduced to 0.4Mpa, and the reaction was carried out for 4 hours. Remove the catalyst by pressure filtration, pour the filter pressure into a 200L glass-lined reactor to cool down to room temperature, adjust the solution to clarification with dilute hydrochloric acid under stirring, cool down to -5°C with ice-salt water, and dropwise add 12kg of 30% Sodium nitrite aqueous solution, drop in about 15 minutes (PH should be below 1), take a small amount of reaction solution on the drop plate to measure the end point, so that the starch potassium iodide test solution turns blue. Continue stirring for 10 minutes to retest the endpoint. Add 28.7 kg of aqueous solution made of 2.8 kg of sodium hydr...

Embodiment 3

[0037] Step A: Add 80kg of 95% ethanol, 12kg of p-nitro-N-methylbenzenesulfonamide and 0.7kg of active nickel containing 10% water in a 200L high-pressure reactor equipped with a stirrer and a thermometer, ventilate, and heat up under stirring to 85°C, and the pressure of hydrogen was introduced to 1.0Mpa, and the reaction was carried out for 3 hours. Remove the catalyst by pressure filtration, pour the filter pressure into a 200L glass-lined reactor to cool down to room temperature, adjust the solution to clarification with dilute hydrochloric acid under stirring, cool down to -5°C with ice-salt water, and dropwise add 12kg of 30% Sodium nitrite aqueous solution, drop in about 15 minutes (PH should be below 1), take a small amount of reaction solution on the drop plate to measure the end point, so that the starch potassium iodide test solution turns blue. Continue stirring for 10 minutes to retest the endpoint. Add 28.7 kg of aqueous solution made of 2.8 kg of sodium hydrosu...

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Abstract

The invention relates to a preparation method of 3-(2-aminoethyl)-N-methyl-1H-indole-5-methanesulfonamide and belongs to the field of preparation of medicament intermediates. The preparation method comprises the following steps: carrying out catalytic hydrogenation and reduction on p-nitrobenzene methanesulfonamide; diazotizing and then cooling; and carrying out thermal reduction, condensation and cyclization, thus obtaining the 3-(2-aminoethyl)-N-methyl-1H-indole-5-methanesulfonamide. In the preparation process, intermediate products of each reaction are not separated so as to directly prepare the 3-(2-aminoethyl)-N-methyl-1H-indole-5-methanesulfonamide. The preparation method has the following advantages: the process is stable, the operation is simple, reaction conditions are easy to control and reaction steps are less; the intermediate products in the reaction process are not separated so as to directly participate in reaction; the after treatment is simple and convenient, three wastes are less, and a mother solution can be continuously recycled; the product quality is good, the yield is high and the manufacturing cost is low; and the method is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of 3-(2-aminoethyl)-N-methyl-1H-indole-5-methanesulfonamide, which belongs to the field of preparation of pharmaceutical intermediates. Background technique [0002] The preparation method of the relevant report 3-(2-aminoethyl)-N-methyl-1H-indole-5-methanesulfonamide of existing literature has the following several kinds: (1) British Patent GB2124210 provides the use of PdO / C. The preparation method of hydrogenation reduction of 4-nitro-N-methylbenzenesulfonamide: the solvent is a mixed solvent of ethanol, water and hydrochloric acid to obtain 4-amino-N-methylbenzenesulfonamide hydrochloride. (2) The literature Heterocycles, 1998, 48 (6), 1139-1149 reported that after protecting the amino group with ethyl chloroformate from 4-nitro-N-methylbenzenesulfonamide, it was reduced by nitro, diazotized, Reduction reaction produces hydrazine compounds. [0003] There are many shortcomings in the above methods, w...

Claims

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Application Information

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IPC IPC(8): C07D209/14
Inventor 朱连博郑忠辉赵帅徐雪梅
Owner SHANDONG XINHUA PHARMA CO LTD