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Preparation process for intermediate of acetazolamide

A technology for acetazolamide and intermediates, which is applied in the field of preparing acetazolamide intermediates, can solve the problems of low actual yield, failure to reach the yield value, low product yield, etc., and achieve mature technology and operability Strong, solve the effect of low product qualification rate

Active Publication Date: 2017-09-05
常州金澄医药化工有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] However, in the technical routes of the existing reports, the problem of low product yield generally exists, and the yield value reported in the literature cannot be reached in actual production.
The main reason for the low actual yield is the presence of 2,5-diamino-1,3,4-thiadiazole in the cyclization product intermediate 2-amino-5-mercapto-1,3,4-thiadiazole impurities, and because the two cyclization products are highly similar in the main structure, there are similar and compatible situations with each other, so even after multiple procedures, the 2,5-diamino-1,3,4-thiadiazole impurities Still not easy to be separated from the target product, thereby reducing the qualified rate of subsequent acetazolamide products

Method used

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  • Preparation process for intermediate of acetazolamide

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Add 1.5L of pyridine, 300mL of piperidine, 100g of thiosemicarbazide and 132.6mL of carbon disulfide in a 3L three-necked flask, stir, heat to a temperature of 80°C in the bottle, and react for 5 hours. After the reaction, distill off the solvent and excess carbon disulfide. Gained solid adds 350mL sodium hydroxide solution (solute mass fraction is 20%) to dissolve, adds 2.9g active carbon decolorization 0.5 hour under 60 ℃, decolouring finishes, filters, and adding 135mL solute mass fraction in the gained filtrate is after the hydrochloric acid solution of 37%. A large amount of solids precipitated, stirred for 0.5 hours and filtered, the filter cake was washed three times with water, and dried under reduced pressure at 60°C for 4 hours to obtain 110 g of 2-amino-5-mercapto-1,3,4-thiadiazole with a purity of 99.7% .

[0020] After testing: the melting point of the product is 231-231.5°C; elemental analysis: theoretical value (C 18.03%, H 2.27%, N31.55%, S 48.15%), meas...

Embodiment 2

[0025] Add 1.5L of pyridine, 300mL of piperidine, 100g of thiosemicarbazide and 149.2mL of carbon disulfide in a 3L three-necked flask, stir, heat to a temperature of 80°C in the bottle, and react for 5 hours. After the reaction, distill off the solvent and excess carbon disulfide. Gained solid adds 350mL sodium hydroxide solution (solute mass fraction is 20%) to dissolve, adds 2.9g active carbon decolorization 0.5 hour under 60 ℃, decolouring finishes, filters, and adding 135mL solute mass fraction in the gained filtrate is after the hydrochloric acid solution of 37%. A large number of solids precipitated, stirred for 0.5 hours, filtered, washed the filter cake three times, and dried under reduced pressure at 60°C for 4 hours to obtain 118.2 g of 2-amino-5-mercapto-1,3,4-thiadiazole with a purity of 99.6 %.

[0026] After testing: the melting point of the product is 230-231°C; elemental analysis: theoretical value (C 18.03%, H 2.27%, N31.55%, S 48.15%), measured value (C 18.0...

Embodiment 3

[0031] Add 1.5L of pyridine, 300mL of piperidine, 100g of thiosemicarbazide and 165.8mL of carbon disulfide in a 3L three-necked flask, stir, heat to a temperature of 80°C in the bottle, and react for 5 hours. After the reaction, distill off the solvent and excess carbon disulfide. Gained solid adds 350mL sodium hydroxide solution (solute mass fraction is 20%) to dissolve, adds 2.9g active carbon decolorization 0.5 hour under 60 ℃, decolouring finishes, filters, and adding 135mL solute mass fraction in the gained filtrate is after the hydrochloric acid solution of 37%. A large amount of solids precipitated, stirred for 0.5 hours and filtered, the filter cake was washed three times with water, and dried under reduced pressure at 60°C for 4 hours to obtain 117.1 g of 2-amino-5-mercapto-1,3,4-thiadiazole with a purity of 99.7 %.

[0032] After testing: the melting point of the product is 231-231.5°C; elemental analysis: theoretical value (C 18.03%, H 2.27%, N31.55%, S 48.15%), me...

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Abstract

The invention especially relates to a preparation process for an intermediate of acetazolamide, belonging to the field of medicine synthesis. The process comprises the following steps: with thiosemicarbazide and carbon disulfide as reactants and a mixture of pyridine and piperidine as a solvent, carrying out a reaction; and then successively carrying out purification and drying so as to obtain 2-amino-5-mercapto-1,3,4-thiadiazole, i.e., the intermediate of acetazolamide.

Description

technical field [0001] The invention belongs to the field of pharmaceutical synthesis, in particular to a process for preparing an acetazolamide intermediate. Background technique [0002] Acetazolamide is a new type of non-mercury diuretic. Its mechanism of action is to exert a diuretic effect by inhibiting carbonic dehydratase. Later, there were clinical reports. It also has a good therapeutic effect. [0003] Acetazolamide was first synthesized by Miller et al. in 1950, and its synthesis method is: [0004] [0005] 2-Amino-5-mercapto-1,3,4-thiadiazole is a key intermediate for the synthesis of acetazolamide. At present, almost all the preparation processes of acetazolamide are reported through the acetylation of the intermediate, chlorine obtained through the three processes of oxidation and ammoniation. [0006] However, in the technical routes reported at present, there is generally the problem of low product yield, and the yield value reported in the literature ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D285/135
CPCC07D285/135
Inventor 刘世领杨志刚
Owner 常州金澄医药化工有限公司
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