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Preparation method of rizatriptan benzoate intermediate

A technology for rizatriptan benzoate and intermediates, which is applied in the field of preparation of rizatriptan benzoate intermediates, can solve the problems of not being suitable for ordinary factory production, high equipment requirements, and high risk, and meet the equipment requirements Low cost, safe and simple operation, and easy purification effect

Active Publication Date: 2011-07-20
TIANJIN WEIJIE TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] The advantage of this preparation method is that the yield is high, but the disadvantage is that hydrogen needs to be used in the reaction process, and the reaction is carried out under high pressure conditions, so the potential danger during operation is relatively large, and the requirements for equipment are relatively high, so it is not suitable Production in ordinary factories

Method used

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  • Preparation method of rizatriptan benzoate intermediate

Examples

Experimental program
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Effect test

Embodiment 1

[0032] Under ice-bath conditions, put 34g stannous chloride dihydrate (0.15mol) and 45ml concentrated hydrochloric acid in a 250ml flask equipped with a reflux condenser, a thermometer and an electric stirrer, then lower the temperature to 5°C Next, add 10.2g (0.05mol) 1-(4-nitrophenyl)methyl-1,2,4-triazole, remove the ice bath after the addition, and when the temperature of the solution rises slowly to 60°C, the solution There are still some solids that do not dissolve, and the heating is maintained at 60 ° C for 30 minutes to dissolve all the solids, then stop heating, cool to room temperature, and then adjust the pH of the reaction solution with 40% sodium hydroxide solution under ice bath conditions. value was adjusted to about 13, then the reaction solution was extracted with 200ml×3 times of ethyl acetate, the organic phases were combined, and then dried with anhydrous sodium sulfate, and the solvent was removed to obtain 7.7g of solid 1-(4-aminophenyl ) methyl-1,2,4-tri...

Embodiment 2

[0035] Under ice-bath conditions, put 2.3g stannous chloride dihydrate (0.01mol) and 4.5ml concentrated hydrochloric acid in the 50ml flask that reflux condenser, thermometer and electromagnetic stirrer are equipped with, then reduce the temperature to Below 5°C, add 1g (0.005mol) 1-(4-nitrophenyl)methyl-1,2,4-triazole, remove the ice bath after the addition, and when the temperature of the solution rises slowly to 60°C, the There are still some solids that do not dissolve, and the heating is maintained at 60 ° C for 30 minutes, so that all the solids are dissolved, then the heating is stopped, cooled to room temperature, and the pH value of the reaction solution is adjusted to 13 or so, then extract the reaction liquid with 10ml×3 times of isobutyl acetate, combine the organic phases, dry the organic phases with anhydrous sodium sulfate, and remove the solvent to obtain 0.42g of solid 1-(4-aminophenyl)methyl - 1,2,4-triazole crude product, then dissolve the above crude produc...

Embodiment 3

[0037] Under ice bath conditions, put 226g of stannous chloride dihydrate (1mol) and 1000ml of concentrated hydrochloric acid in a 500ml flask equipped with a reflux condenser, a thermometer and an electric stirrer, and then lower the temperature to below 5°C , and then add 10.2g (0.05mol) 1-(4-nitrophenyl)methyl-1,2,4-triazole, remove the ice bath after the addition, and when the temperature of the solution rises slowly to 60°C, the solution There are still some solids that do not dissolve, and the heating is maintained at 60 ° C for 30 minutes to dissolve all the solids, then stop heating, cool to room temperature, and then adjust the pH of the reaction solution with 40% sodium hydroxide solution under ice bath conditions. The value was adjusted to about 13, then the reaction solution was extracted with 400ml×3 ethers, the organic phases were combined, then dried with anhydrous sodium sulfate, and the solvent was removed to obtain 6.5g of solid 1-(4-aminophenyl)methanol base...

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Abstract

The invention discloses a preparation method of a rizatriptan benzoate intermediate. In the method, stannous chloride or a stannous chloride dihydrate and concentrated hydrochloric acid are used for reducing 1-(4-nitrobenzophenone)methyl-1,2,4-triazole to obtain 1-(4-amidophenyl)methyl-1,2,4-triazole, and the product is an important intermediate for preparing rizatriptan benzoate. The preparationmethod has the advantages of safe and convenient operation, easy purification, high product purity and yield, low impurity content, lower requirement on equipment, and the like. In addition, the purity of rizatriptan benzoate synthesized by the intermediate can reach more than 99.5 percent, and the content of a single impurity is lower than 0.1 percent.

Description

technical field [0001] The invention belongs to the technical field of medicines, in particular to a preparation method of a rizatriptan benzoate intermediate. Background technique [0002] The key intermediate for the preparation of rizatriptan benzoate is a chemical name called 1-(4-aminophenyl)methyl-1,2,4-triazole, with the compound of the following general formula II: [0003] [0004] At present, there are four preparation methods of 1-(4-aminophenyl)methyl-1,2,4-triazole which have been reported in the literature. [0005] The European patent EP0573221 that Merck Company applied for in 1993 discloses a kind of preparation method of this intermediate, and its synthetic route is as follows: [0006] [0007] The advantage of this preparation method is that the yield is very high, but the disadvantage is that a large amount of organic solvent is used in the post-treatment, so repeated extraction and washing are required, so the operation process is cumbersome. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D403/06C07D249/08
Inventor 宋洪海白振锋陈伟裴江邹阳
Owner TIANJIN WEIJIE TECH