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Preparation method of 6-bromo-3-hydroxy-2-pyrazinecarboxamide

A technology of pyrazine carboxamide and carbamoyl pyrazine, which is applied in the field of preparation of 6-bromo-3-hydroxy-2-pyrazine carboxamide, can solve the problems of idle instruments, reduced production efficiency, and low conversion rate of raw materials, and achieves The effect of cleaning the reaction route, simplifying the production operation and shortening the reaction time

Pending Publication Date: 2021-08-10
河北唯达生物医药产业技术研究有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

It is currently known that 6-bromo-3-hydroxyl-2-pyrazinamide is the main raw material used to prepare 6-fluoro-3-hydroxyl-2-pyrazinamide, and the patent with the authorized announcement number of CN 102307865B proposes a The preparation method of chloropyrazine derivatives, and the synthetic method of 6-bromo-3-hydroxypyrazine-2-carboxamide is provided, in the cooling 2-aminomalonic acid diamide sodium hydroxide aqueous solution, drop ethylene di Aldehyde solution, stirring repeatedly to obtain 2-carbamoylpyrazine-3-hydroxyl sodium, then suspending 2-carbamoylpyrazine-3-hydroxyl sodium in a mixture of methanol and acetonitrile or ethyl acetate, and Add bromine dropwise and stir to filter out the solid product to obtain 6-bromo-3-hydroxypyrazine-2-carboxamide. Another example is the patent of CN111978263A, which uses a microchannel reactor to prepare 6-bromo-3-hydroxypyrazine-2 - formamide, its reaction operation is simple, energy-saving, and the yield can reach 90.0%, but the microchannel reactor is expensive, not suitable for large-scale use, and there are not many suitable reactions, which may easily cause the instrument to be idle
[0003] In the existing process of preparing 6-bromo-3-hydroxyl-2-pyromerazinamide, tetrabutylammonium bromide is used to replace bromine, and tetrabutylammonium bromide needs to be continuously added in the reaction process, thereby The overall reaction time is prolonged, the production efficiency is reduced, and due to the continuous addition of raw materials, the conversion rate of the raw materials will be low, resulting in a reduction in the yield of the product

Method used

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  • Preparation method of 6-bromo-3-hydroxy-2-pyrazinecarboxamide

Examples

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Embodiment 1

[0022] 1) Add methanol (160kg) and acetonitrile (600kg) to the reactor, stir and add 2-carbamoylpyrazine-3-hydroxysodium (161kg) and tetrabutylammonium bromide (16kg);

[0023] 2) Control the temperature of the system at 30-35°C, and slowly add liquid bromine to the system dropwise. After the dropwise addition, control the temperature of the system at 30-35°C, and stir for 4 hours. The bromine color of the reaction system will fade away. Use TLC to spot the reaction. whether it is completed;

[0024] 3) After the reaction is completed, cool the reaction solution to 0-10°C, and slowly add cooling water dropwise;

[0025] 4) After adding the cooling water dropwise, continue to stir and crystallize at 0-10°C for 2 hours, centrifuge, rinse with an appropriate amount of drinking water during the centrifugation process, and obtain a light yellow solid wet product;

[0026] 5) The wet product was air-dried at 70-80° C., and collected to obtain 181 kg of light yellow solid, with a yi...

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Abstract

The invention discloses a method for preparing 6-bromine-3-hydroxyl-2-pyrazinecarboxamide by using 2-carbamoyl pyrazine-3-sodium hydroxide, and belongs to the field of chemical engineering. The method comprises the following steps: dissolving 2-carbamoyl pyrazine-3-sodium hydroxide and a catalyst in a solvent, dropwise adding a bromine reagent, performing stirring to react to generate 6-bromine-3-hydroxyl-2-pyrazinecarboxamide, performing stirring and crystallizing in ice water, and performing filtering to obtain a pure product of 6-bromo-3-hydroxyl-2-pyrazinecarboxamide. Compared with a traditional method, the method for dropwise adding bromine water has the advantages that the reaction time is greatly shortened, the production operation is simplified, the production efficiency is improved, the whole reaction route is clean and environment-friendly, and the method is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of chemical industry, in particular to a preparation method of 6-bromo-3-hydroxy-2-pyrazine carboxamide. Background technique [0002] 6-Fluoro-3-hydroxy-2-pyrazinecarboxamide is a compound used for preventing and treating viral infectious diseases, especially influenza virus infectious diseases. It is currently known that 6-bromo-3-hydroxyl-2-pyrazinamide is the main raw material used to prepare 6-fluoro-3-hydroxyl-2-pyrazinamide, and the patent with the authorized announcement number of CN 102307865B proposes a The preparation method of chloropyrazine derivatives, and the synthetic method of 6-bromo-3-hydroxypyrazine-2-carboxamide is provided, in the cooling 2-aminomalonic acid diamide sodium hydroxide aqueous solution, drop ethylene di Aldehyde solution, stirring repeatedly to obtain 2-carbamoylpyrazine-3-hydroxyl sodium, then suspending 2-carbamoylpyrazine-3-hydroxyl sodium in a mixture of methanol and acetonitri...

Claims

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Application Information

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IPC IPC(8): C07D241/24
CPCC07D241/24
Inventor 瞿鑫马良
Owner 河北唯达生物医药产业技术研究有限公司
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