New process for preparing telmisartan

A technology of telmisartan and a new process, applied in the field of organic chemistry, can solve problems such as inability to use industrialized production, and achieve the effects of good product quality, shortened reaction time, and high yield

Inactive Publication Date: 2011-12-07
张长利
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The technical problem to be solved in the present invention is to overcome the technical difficulties that the prior art cannot be used for industrialized production, and provide a new process for preparing telmisartan, which is simple in operation, green in synthesis, and has high purity and high yield of telmisartan , low cost, suitable for industrial production

Method used

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  • New process for preparing telmisartan
  • New process for preparing telmisartan
  • New process for preparing telmisartan

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1: 4'-[(1,4'-dimethyl-2'-propyl[2,6'-di-1H-benzimidazole]-1'-yl)methyl]-[1, 1'-biphenyl]-2-carboxylic acid (Compound III, Telmisartan)

[0025] Put 50g compound I, 200ml dimethylsulfoxide (DMSO) into a 500ml reaction bottle, stir and dissolve at room temperature, add 55g, 4'-bromomethylbiphenyl-2-carbonitrile and 40gNaOH, 40ml dimethylsulfoxide (DMSO) React at about 25-30°C for 2 hours, raise the temperature to 160°C and react for 8 hours, after the reaction is completed, cool naturally, add glacial acetic acid to crystallize, filter to obtain 301g of crude telmisartan (wet weight)

[0026] Put 301g of crude telmisartan into a 1000ml reaction bottle, add 500ml of ethanol and 30ml of ammonia water to heat and dissolve, add 3g of activated carbon for decolorization for 30 minutes, filter, cool to room temperature, add glacial acetic acid to crystallize, filter, and dry to obtain 72.5g of telmisartan. Misartan fine product, the yield is 85.6%, the HPLC purity is 9...

Embodiment 2

[0027] Example 2: 4'-[(1,4'-dimethyl-2'-propyl[2,6'-di-1H-benzimidazole]-1'-yl)methyl]-[1, 1'-biphenyl]-2-carboxylic acid (Compound III, Telmisartan)

[0028] Put 50g of compound I and 200ml of dimethylformamide (DMF) into a 500ml reaction flask, stir at room temperature for 10 minutes, add 52g of 4'-bromomethylbiphenyl-2-carbonitrile and 40g of Na 2 CO 3 , 40ml of dimethylformamide (DMF), 25 ~ 30 ℃ for about 2 hours, heated up to 140 ℃ for 8 hours, after the reaction was completed, cooled naturally, added hydrochloric acid to crystallize, filtered to get 319g telmisartan crude product (wet Heavy).

[0029] Put 319g of crude telmisartan into a 1000ml reaction bottle, add 500ml of ethanol and 35ml of ammonia water to heat and dissolve, add 5g of activated carbon for decolorization for 30 minutes, filter, cool to room temperature, add glacial acetic acid to crystallize, filter, and dry to obtain 70.14g The refined product of telmisartan has a yield of 82.9%, an HPLC purity of...

Embodiment 3

[0030] Example 3: 4'-[(1,4'-dimethyl-2'-propyl[2,6'-di-1H-benzimidazol]-1'-yl)methyl]-[1, 1'-biphenyl]-2-carboxylic acid (Compound III, Telmisartan)

[0031] Drop into 50kg compound I, 300 liters of ethylene glycol in 1000 liters reactor, stir at room temperature for 10 minutes, add 55kg4'-bromomethylbiphenyl-2-carboxylate methyl ester and 40kg potassium hydroxide, 50 liters of ethyl alcohol Diol, 25~30 DEG C left and right reaction 2 hours, be warming up to 50 DEG C and react 3 hours, after completion of reaction, natural cooling, add glacial acetic acid crystallization, filter, obtain 328kg telmisartan crude product (wet weight).

[0032] Put 328 kg of crude telmisartan into a 1000 liter reactor, add 500 liters of ethanol and 50 liters of ammonia water, heat to dissolve, add 5 kg of activated carbon for decolorization for 30 minutes, cool to room temperature, add glacial acetic acid to crystallize, filter and dry , to obtain 79.2kg of fine telmisartan, yield 93.6%, HPLC pur...

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Abstract

The invention relates to a new process for preparing telmisartan, which uses 2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2'-yl)-benzimidazole and 4' -Bromomethyl-biphenyl-2-carboxylate alkyl ester or 4'-bromomethyl-biphenyl-2-carbonitrile undergoes a one-step reaction to complete the two-step synthesis reaction of condensation and hydrolysis to directly obtain Telmisartan. Compared with other processes, it has the advantages of solving the technical difficulties of industrial production, simple operation, green synthesis, high purity of telmisartan, high yield and low cost, and has been successfully applied in industrial production.

Description

technical field [0001] The invention belongs to the field of organic chemistry, and specifically relates to a new preparation process for synthesizing high-purity telmisartan through one-step reaction to complete condensation and hydrolysis. Background technique [0002] Telmisartan is an angiotensin II receptor antagonist. The scientific name of telmisartan is 4'-[(1,4'-dimethyl-2'-propyl[2,6'-di-1H-benzimidazole]-1'-yl)methyl]- [1,1'-biphenyl]-2-carboxylic acid, the structural formula is: [0003] [0004] The drug was developed by Boehringer Ingelheim of Germany, and it was first listed in the United States in 1998, and then approved to be listed in other countries in the world. The trade name is Micardis. [0005] Telmisartan is usually prepared and sold as the free acid or sodium salt. As shown in WO2004087676A, crystalline Telmisartan exists in two polymorphic forms with different melting points. The lower melting point polymorphic form B is irreversibly changed...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D235/18
Inventor 张长利焦佩玉
Owner 张长利
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