Multi-nitrogen heterocycle thiadiazoles-5-formamidine compound by cyclization method

A technology of compound and target compound, which is applied in the field of synthesis of 1,2,3-thiadiazole-5-carboxamidine compounds, can solve the problems of large spatial position, low reactivity, and complex components, so as to reduce the amount of production, The effect of good product quality and high synthesis yield

Inactive Publication Date: 2015-08-26
XIHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The combined dehydration catalyst not only has complex components, but also has a high price, and at the same time, a large amount of phosphorus-containing wastewater is produced in the post-treatment process
At the same time, the patent (application number CN2015100098343) also analyzed that the main reason for using such a complex and highly active combined catalyst is because the synthesis reported TDCA The target compound is an N-trisubstituted-1,2,3-thiadiazole-5-carboxamidine compound with three aromatic rings, and it is necessary to use the compound B As a raw material, however, the raw material compound B Large spatial location, low reactivity

Method used

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  • Multi-nitrogen heterocycle thiadiazoles-5-formamidine compound by cyclization method
  • Multi-nitrogen heterocycle thiadiazoles-5-formamidine compound by cyclization method
  • Multi-nitrogen heterocycle thiadiazoles-5-formamidine compound by cyclization method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Synthesis of 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride (compound Q ):

[0043] 1) Synthesis of ethyl carbazate:

[0044] Add 540ml (4.4mol) of diethyl carbonate and 255g (4mol) of 80% hydrazine hydrate into a 2000ml three-necked round bottom flask equipped with a condensing reflux tube, stir, and gradually raise the temperature to 50°C, the reaction system changes from turbid to clear liquid, keep the temperature and stir for 1 hour, lower to room temperature and continue to stir for 24 hours, distill ethanol and water under reduced pressure (remove the water brought in by ethanol and hydrazine hydrate), and dry in vacuum to obtain 399.2 g of white solid product, which is directly processed Next reaction.

[0045] 2) Synthesis of ethyl 3-(ethoxycarbonyl-hydrazone)butanoate

[0046] Add 508 mL (4 mol) of ethyl acetoacetate into a 2000ml three-neck flask, stir magnetically, and add 399.2 g of ethyl carbazate dropwise over 2 hours under ice water cooling (prepared ...

Embodiment 2

[0053] Synthesis of N-methyl-4-methyl-1,2,3-thiadiazole-5-carboxamide (compound P ):

[0054] Add 162.6 g (1.00 mol) of 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride (compound Q ), 37.3 g (1.20 mol) methylamine, 1000 mL toluene. Heat to 100°C, absorb the hydrogen chloride gas produced by the reaction with lye, react for 10 h, cool the reaction system to room temperature, pour the reaction solution into an equal volume of water, and adjust the pH value of the obtained mixture with 2% sodium hydroxide aqueous solution, Make it pH=7. Separate the liquid to obtain a toluene solution containing N-methyl-4-methyl-1,2,3-thiadiazole-5-carboxamide, distill and concentrate the toluene solution to obtain a brown solid N-methyl-4-methyl- The crude product of 1,2,3-thiadiazole-5-carboxamide was 155.6 g, the liquid phase normalized purity was 97.9%, and the yield was 99%. The crude brown solid N-methyl-4-methyl-1,2,3-thiadiazole-5-carboxamide does not need further purification and can ...

Embodiment 3

[0056] Synthesis of N'-(2,6-difluoropyridin-4-yl)-N,4-dimethyl-1,2,3-thiadiazole-5-carboxamidine (compound N-10 ) (X=F, Y=F in Formula 8):

[0057]

[0058] Under the condition of nitrogen protection, 200ml of anhydrous sulfolane, 2,6-difluoro-4-aminopyridine (13.0g, 100mmol), compound P (N-methyl-4-methyl-1 , 2,3-thiadiazole-5-carboxamide) (15.7g, 100mmol), add freshly distilled thionyl chloride (35.7g, 300mmol), DCC (dicyclohexylcarbodiimide) (20.7g, 100mmol ) after heating to 75°C for 12 hours, the reaction was changed from a reflux device to a distillation device, and the low-boiling components in the reactor were distilled (the main component was unreacted thionyl chloride), and the temperature was raised to 100°C for 3 hours, and then stopped reaction. Cool slightly, pour the reaction solution into a large amount of crushed ice, adjust pH=7 with 1M aqueous sodium hydroxide solution, filter with suction, and recrystallize the obtained product with a mixed solvent of ...

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Abstract

The invention discloses an N-trisubstituted-1,2,3-thiadiazoles-5-formamidine target compound of which the general formula is TDCA. The N-trisubstituted-1,2,3-thiadiazoles-5-formamidine target compound is obtained from an M compound through a cyclization reaction. The new synthetizing method is high in yield, catalysts are easy to prepare, the catalysts are low in cost, phosphoric waste water is less, and the multi-nitrogen heterocycle thiadiazoles-5-formamidine compound is environment-friendly. (As shown in the Description).

Description

technical field [0001] The present invention relates to a method for synthesizing 1,2,3-thiadiazole-5-carboxamidine compounds, in particular to a new synthesis method for 1,2,3-thiadiazole-5-carboxamidine compounds containing three nitrogen heterocycles . Background technique [0002] Amidines have a wide range of applications in medicine, and can be used as drugs for treating diabetes, cardiovascular diseases, anti-inflammatory drugs, anthelmintics and diuretics. Amidines are also widely used in agriculture. For example, the British Boots company has developed a new low-toxicity, broad-spectrum organic nitrogen acaricide with two amidine functional group structures, which has strong contact, fumigation and good penetration effects, and can be used for The prevention and treatment of ticks, mites, scabies, etc. parasitic on livestock has a good development prospect. [0003] Due to the wide application of amidines, especially in pharmaceuticals and pesticides, there are m...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D417/14
CPCC07D417/14
Inventor 杨维清刘萍张园园任川洪张燕
Owner XIHUA UNIV
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