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Continuous synthesis method of rufinamide

A technology for rufinamide and chemical synthesis, which is applied in the field of drug synthesis and can solve the problems of high cost, low product yield, low safety and the like

Active Publication Date: 2020-10-30
ASYMCHEM LAB TIANJIN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0019] The main purpose of the present invention is to provide a continuous synthesis method of rufinamide to solve the problems of low safety, high cost and low product yield in the existing method for preparing rufinamide

Method used

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preparation example Construction

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

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

Embodiment 1

[0049] Dissolve methyl 1,2,3-triazole-4-carboxylate (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 (coil pipe, long 25.5 meters, That is, 2,6-difluorobenzyl chloride (8.1g, 0.05mol) dissolved in chloroform (19g, 2V) is pumped into the first continuous reaction device with a speed of 1.86g / min by pump B in the coil tube with a diameter of 3mm , and the first continuous reaction device is immersed in a 75°C oil bath, the retention time of the reaction raw materials is 30min, the pressure in the first continuous reaction device is 0.6MPa, and the continuous condensation product system is obtained, wherein 1, 2, The molar ratio of 3-triazole-4-carboxylic acid methyl ester, triethylamine and 2,6-difluorobenzyl chloride is 1:1.2:1.

[0050] The above-mentioned continuous condensation product system directly enters the second continuous reaction device (coil pipe, lon...

Embodiment 2

[0053] Dissolve methyl 1,2,3-triazole-4-carboxylate (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 (coil pipe, long 25.5 meters, That is, 2,6-difluorobenzyl chloride (8.1g, 0.05mol) dissolved in chloroform (19g, 2V) is pumped into the first continuous reaction device with a speed of 1.86g / min by pump B in the coil tube with a diameter of 3mm , and the first continuous reaction device is immersed in an oil bath at 100°C, the retention time of the reaction raw materials is 30min, and the pressure in the first continuous reaction device is 0.6MPa to obtain a continuous condensation product system, wherein 1, 2, The molar ratio of 3-triazole-4-carboxylic acid methyl ester, triethylamine and 2,6-difluorobenzyl chloride is 1:1.2:1.

[0054] The above-mentioned continuous condensation product system directly enters the second continuous reaction device (coil pipe, lon...

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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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Patent Type & Authority Patents(China)
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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