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Methimazole preparation method

A technology of methimazole and methylamine, applied in the field of preparation of methimazole, can solve the problems of unfriendly environment, high production cost, not allowing benzene and the like, and achieve the effects of being environmentally friendly, easy to operate and low cost

Inactive Publication Date: 2017-11-17
BEIJING WANPENGLANGGE PHARMA TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The extraction efficiency of benzene is very low in the actual operation process, which is not friendly to the environment
[0005] To sum up, at present domestic production of methimazole mainly adopts bromoacetaldehyde diethyl acetal, which has low yield and high production cost; if chloroacetaldehyde dimethyl acetal is used for production, the intermediate methylaminoacetaldehyde The extraction of dimethanol with benzene is very difficult and requires repeated extractions, and the domestic production of raw materials has not allowed a class of highly toxic solvents such as benzene

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] 1) Methanization: Add 3.00kg of chloroacetaldehyde dimethylacetal and 30kg of 33% methylamine methanol solution into the autoclave, close the autoclave valve, heat to 130-135℃, the maximum pressure is 1.2MPa, and then continue to decrease , Keep the temperature for 6 hours, lower the temperature to 25℃, and press to the neutralization tank. Stir and lower the temperature to below 10°C, add dropwise 3.26kg of 40% sodium methoxide methanol solution, and keep at 0-5°C for 2-3 hours. Filter, wash the filter cake with methanol, and transfer the filtrate to a distillation tank. Distill methanol at atmospheric pressure until it is no longer distilled out, change to vacuum distillation, turn on brine condensation to collect the intermediates, collect the 52-60℃ / 24mmHg fraction, obtain 2.51kg methylamino acetaldehyde dimethyl acetal, GC purity 94.6 %, the yield was 83.1%.

[0033] 2) Cycling:

[0034] Put 1.44kg sodium thiocyanate and 8.9kg purified water into the cyclization reac...

Embodiment 2

[0036] 1) Methanation:

[0037] Add 3.00kg of chloroacetaldehyde dimethylacetal and 30kg of 33% methylamine methanol solution into the autoclave, close the autoclave valve, heat to 120-125℃, the pressure is up to 1.0MPa, and then continue to decrease, keep warm for 10 hours, and cool down To 25℃, press to the neutralization tank. Stir and lower the temperature to below 10°C, add dropwise 3.26kg of 40% sodium methoxide methanol solution, and keep at 0-5°C for 2-3 hours. Filter, wash the filter cake with methanol, and transfer the filtrate to a distillation tank. Distill methanol at atmospheric pressure until it is no longer distilled out, change to vacuum distillation, turn on brine condensation to collect intermediates, collect 52-60°C / 24mmHg fractions, obtain 2.22kg methylaminoacetaldehyde dimethylacetal, and GC purity 93.7 %, the yield is 72.5%.

[0038] 2) Cycling:

[0039] Put 1.44kg sodium thiocyanate and 8.9kg purified water into the cyclization reactor, dissolve under stir...

Embodiment 3

[0041] 1) Methanation:

[0042] Add 3.00kg of chloroacetaldehyde dimethylacetal and 30kg of 33% methylamine methanol solution to the autoclave, close the autoclave valve, heat up to 145-150℃, and pressure up to 1.7MPa, then continue to decrease, keep the temperature for 10 hours, and cool down To 25℃, press to the neutralization tank. Stir and lower the temperature to below 10°C, add dropwise 3.26kg of 40% sodium methoxide methanol solution, and keep at 0-5°C for 2-3 hours. Filter, wash the filter cake with methanol, and transfer the filtrate to a distillation tank. Distill methanol at atmospheric pressure until it is no longer distilled out, change to vacuum distillation, turn on brine condensation to collect the intermediates, collect the 52-60℃ / 24mmHg fraction, and obtain 2.53kg methylaminoacetaldehyde dimethylacetal with a purity of 93.5 by GC %, the yield was 82.7%.

[0043] 2) Cycling:

[0044] Put 1.44kg sodium thiocyanate and 8.9kg purified water into the cyclization reac...

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Abstract

The invention discloses a methimazole preparation method, which comprises: 1) carrying out an ammonolysis reaction on dimethylchloroacetal and a methylamine methanol solution at a temperature of 125-135 DEG C, adding the alkoxide of an alkali metal after completing the reaction, carrying out a neutralization reaction, filtering, distilling to remove the methanol, and carrying out pressure reducing distillation to obtain an intermediate methylamino dimethoxyethane; and 2) adding sodium thiocyanate and the methylamino dimethoxyethane obtained in the step 1) into purified water, adding hydrochloric acid at a room temperature in a dropwise manner, carrying out a reaction for 12-15 h at a temperature of 50-60 DEG C, carrying out pressure reducing distillation to remove the water after completing the reaction, adding ethyl acetate and a drying agent, carrying out heating reflux for 30 min, carrying out hot filtering, distilling the filtrate until the remaining volume of the ethyl acetate is 1 / 3, and carrying out cooling crystallization to obtain the methimazole. According to the present invention, the preparation method has advantages of low cost, short route, convenient operation and environmental protection, and the high-quality methimazole can be obtained through the method.

Description

Technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a method for preparing methimazole. Background technique [0002] Methimazole is also known as tapazole and its chemical name is 1-methylimidazole-2-thiol. It is an antithyroid drug. Its mechanism of action is to inhibit peroxidase in the thyroid, thereby preventing the absorption of iodide into the thyroid. The coupling of oxidation and tyrosine hinders the synthesis of thyroxine (T4) and triiodothyronine (T3). Animal experiments have observed that B lymphocytes synthesize antibodies, reduce the level of thyroid stimulating antibodies in the blood circulation, and restore suppressor T cells to normal. It is suitable for various types of hyperthyroidism. Its effect is stronger than that of propylthiouracil (the dose is 1 / 10 of propylthiouracil, but the effect is 20 times), and it works quickly but metabolizes slowly and lasts for a long time. [0003] Chinese patent CN201210...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D233/84
CPCC07D233/84
Inventor 李淑君高国章李亚玲
Owner BEIJING WANPENGLANGGE PHARMA TECH
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