Preparation technology of telmisartan active pharmaceutical ingredient

A technology for preparing telmisartan and its preparation technology, which is applied in the field of preparation technology of telmisartan raw material medicine, can solve problems such as environmental pollution, complicated operation, and cost reduction, and achieve industrial production convenience, high income, and simple preparation process route Effect

Inactive Publication Date: 2011-03-09
FUZHOU NEPTUNUS FUYAO PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The traditional route of producing the drug has low yield and complex operation, which is not conducive to cost reduction, and there are three wastes pollution, which will cause great pollution to the environment

Method used

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Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0016] A kind of preparation technology of telmisartan crude drug, its process route is: take 3-methyl-4-nitro-benzoic acid as starting material, obtain 4-amino-3-methylbenzene through esterification and reduction Methyl formate, through acylation, fuming nitric acid nitration, reduction, cyclization, hydrolysis to obtain 4-methyl-2-n-propyl-benzimidazole-6-carboxylic acid, and then with N-methyl o-phenylenediamine Condensation produces 4-methyl-2-n-propyl-6-(1-methylbenzimidazol-2-yl)-benzimidazole, and then under the action of potassium tert-butoxide, with 4'-bromomethyl -Biphenyl-2-carboxylate methyl ester is condensed and hydrolyzed by sodium hydroxide solution-methanol system to obtain crude telmisartan.

[0017] The crude product of telmisartan is recrystallized by using dimethylformamide as a solvent to obtain the crude drug of telmisartan.

[0018] The condition for the nitration with fuming nitric acid is that the amount of fuming nitric acid added is 2-3 times that ...

Embodiment 1

[0025] Add 2 mol of 3-methyl-4-nitrobenzoic acid and anhydrous methanol into the reaction flask, slowly add 200mL of concentrated sulfuric acid dropwise under stirring, then stir and heat to reflux for 8hrs, cool, pour the reaction solution into water, and let stand 1hr, filtered, washed with water, and dried to obtain solid product 1 with a yield of 90%. Add 1 mol of solid product 1, 5% Pd / C 4g and methanol into a 2L hydrogenation kettle, hydrogenate at room temperature and 3.5atm until no hydrogen is absorbed, filter and recover the catalyst, distill the filtrate to remove methanol and solidify, then use 95% ethanol Recrystallization gave white solid product 2 with a yield of 90%.

[0026] Take 2 mol of the white solid product 2, add triethylamine and dichloromethane into the reaction flask, cool in an ice-salt bath, add n-butyryl chloride dropwise under stirring, and control the temperature not to exceed 10°C. After dropping, the temperature was naturally raised to room te...

Embodiment 2

[0030] The condition for the nitration with fuming nitric acid is that the amount of fuming nitric acid added is twice that of 3-methyl-4-nitro-benzoic acid.

[0031] The sodium hydroxide solution-methanol system is hydrolyzed, the mass concentration of the sodium hydroxide solution is 5%, the volume ratio of the sodium hydroxide solution to methanol is 2:1, and the time is 1.5 hours.

[0032] Dissolve the obtained crude telmisartan in dimethylformamide, the solid-to-liquid ratio of the two is 1:3, filter, and vacuum-dry the filtrate at 70°C to obtain the telmisartan raw material.

[0033] The prepared telmisartan bulk drug can be prepared into tablets as required, and the telmisartan bulk drug is mixed with purified water, wetting agent, binding agent, disintegrating agent and lubricant, and prepared under a conventional process Telmisartan tablet.

[0034] The parts not mentioned above are the same as the specific embodiment.

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PUM

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Abstract

The invention relates to a preparation technology of a telmisartan active pharmaceutical ingredient, which comprises the technological routes: taking 3-methyl-4-nitryl-benzoic acid as an initial raw material; preparing 4-amino-3-methyl benzoic acid methyl ester through esterification and reduction; preparing 4-methyl-2-propyl-benzimidazole-6-carboxylic acid through acylation, nitration of fuming nitric acid, reduction, cyclization and hydrolysis; producing 4-methyl-2-propyl-6-(1-benzimidazole-methylbenzimidazole-2-yl)-benzimidazo through the condensation with N-methy-o-phenylenediamine; and condensing with 4'-brooethyl biphenyl-2-carboxylic methyl ester in the presence of potassium tert-butoxide and preparing a telmisartan crude product through the hydrolysis of a sodium hydroxide solution-methanol system. The technological routes are simple and mature. The total molar yield can finally reach 23.2% through improving the traditional technological routes; and reaction operation is more easier, the process is simpler, serious three-waste pollution is not generated and the preparation technology is convenient for industrial production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical engineering, and more specifically relates to a preparation process of a telmisartan bulk drug. Background technique [0002] Telmisartan (Telmisartan), also known as BIBR277, is an angiotensin II-AT developed by Boehringer Inglheim, Germany 1 Receptor antagonists are a new class of antihypertensive drugs. Angiotensin Ⅱ is formed by angiotensin Ⅰ through the reaction catalyzed by angiotensin-converting enzyme. It is the main pressurizing factor in the renin-angiotensin system. Its effects mainly include causing vasoconstriction and stimulating the synthesis and release of aldosterone. , myocardial excitation and renal tubular sodium reabsorption. The mechanism of action of telmisartan is: it can highly selectively block angiotensin II and AT in many tissues 1 Binding to receptors, thereby blocking the effects of angiotensin II on vasoconstriction and aldosterone secretion, and achieving the effe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D235/18
Inventor 徐燕和徐敏华陈才河曹永辉郭文璟陈瑜
Owner FUZHOU NEPTUNUS FUYAO PHARMA
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