Continuous rufinamide synthesizing method

A technology for the synthesis of rufinamide, which is applied in the field of drug synthesis, can solve problems such as low safety, low product yield, and high cost, and achieve the effects of high heat exchange speed, simplified purification steps, and reduced process costs

Active Publication Date: 2019-03-08
ASYMCHEM LAB TIANJIN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] The main purpose of the present invention is to provide a continuous synthesis method of rufinamide to s

Method used

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Example Embodiment

[0032] As described in the background art, the existing methods for preparing rufinamide have the problems of low safety, high cost, and low product yield. In order to solve the above technical problems, this application provides a continuous synthesis method of rufinamide. The continuous synthesis method includes: in the presence of an acid binding agent, 1,2,3-triazole-4-carboxylate Methyl acid and 2,6-difluorobenzyl chloride are continuously input into the first continuous reaction device for continuous condensation reaction to obtain continuous condensation products, and the continuous condensation products are continuously discharged; the continuous condensation products and ammonia The gas or ammonia-containing solution is continuously fed into the second continuous reaction device to perform the ammonolysis reaction to obtain rufinamide, and the rufinamide is continuously discharged.

[0033] In the first step of the present invention, under the action of the acid binding ...

Example Embodiment

[0048] Example 1

[0049] Dissolve 1,2,3-triazole-4-carboxylic acid methyl ester (6.4g, 0.05mol) and triethylamine (6.1g, 0.06mol) in chloroform (19g, 2V) and stir to clarify, then use Pump A is pumped into the first continuous reaction device (coiled tube, 25.5 meters long, at a speed of 1.81g / min) That is, in a coil with a diameter of 3mm, 2,6-difluorobenzyl chloride (8.1g, 0.05mol) is dissolved in chloroform (19g, 2V) and pumped into the first continuous reactor with pump B at a speed of 1.86g / min The first continuous reaction device was immersed in an oil bath at 75°C, the retention time of the reaction raw materials was 30 minutes, and the pressure in the first continuous reaction device was 0.6 MPa to obtain a continuous condensation product system, of which 1, 2, The ratio of the number of moles of 3-triazole-4-carboxylic acid methyl ester, triethylamine and 2,6-difluorobenzyl chloride is 1:1.2:1.

[0050] Directly enter the above continuous condensation product system int...

Example Embodiment

[0052] Example 2

[0053] Dissolve 1,2,3-triazole-4-carboxylic acid methyl ester (6.4g, 0.05mol) and triethylamine (6.1g, 0.06mol) in chloroform (19g, 2V) and stir to clarify, then use Pump A is pumped into the first continuous reaction device (coiled tube, 25.5 meters long, at a speed of 1.81g / min) That is, in a coil with a diameter of 3mm, 2,6-difluorobenzyl chloride (8.1g, 0.05mol) is dissolved in chloroform (19g, 2V) and pumped into the first continuous reactor with pump B at a speed of 1.86g / min The first continuous reaction device was immersed in an oil bath at 100°C, the retention time of the reaction raw materials was 30 min, and the pressure in the first continuous reaction device was 0.6 MPa to obtain a continuous condensation product system, of which 1, 2, The ratio of the number of moles of 3-triazole-4-carboxylic acid methyl ester, triethylamine and 2,6-difluorobenzyl chloride is 1:1.2:1.

[0054] Directly enter the above continuous condensation product system into t...

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Abstract

The invention provides a continuous rufinamide synthesizing method. The continuous rufinamide synthesizing method comprises, with existence of acid-binding agent, continuously inputting 1, 2, 3-triazole-4-methyl carboxylate and 2, 6-difluorobenzyl chloride into a first continuous reaction device for continuous condensation reaction to obtain continuous condensation products, and continuously discharging the continuous condensation products; continuously inputting the continuous condensation products and ammonia gas or ammonia-containing solution into a second continuous reaction device for ammonolysis reaction to obtain rufinamide, and continuously discharging the rufinamide. The continuous rufinamide synthesizing method not only avoids production of isomers during cyclization of conventional routes to simplify the purification process of finished products, but also effectively reduces the process costs and shortens the reaction route; meanwhile, compared with batch equipment, the continuous rufinamide synthesizing method is implemented in a continuous reaction device; due to the facts the reaction system is small and heat exchange speed is high, reaction conditions can be more intense but safer.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a continuous synthesis method of rufinamide. Background technique [0002] Rufinamide (trade name Banzel) is a drug developed by Swiss Novartis for adjuvant treatment of epilepsy, and it was launched in the United States in November 2008. It is a derivative of triazoles. Its chemical structure is different from that of the currently marketed antiepileptic drugs. It works by regulating the activity of sodium ion channels in the brain. When the concentration of rufinamide is greater than 10 μmol / L, it has no significant effect on monoamines, epinephrine, histamine, acetylcholine, AMPA-kainate, glycine, NMDA or GABA neurotransmitter-receptor system. Clinical studies have shown that adjuvant treatment with rufinamide is well tolerated by epilepsy patients, with a reduction in the number of seizures. Moreover, rufinamide still has an effect on patients with partial or generalized epile...

Claims

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Application Information

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IPC IPC(8): C07D249/04
CPCC07D249/04
Inventor 洪浩卢江平张恩选申慰闫红磊张震
Owner ASYMCHEM LAB TIANJIN
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