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2-propyl-4 methyl-6-(tolimidazole-2group) benzoglioxaline salt and method for producing the same

A technology of methyl benzimidazole and benzimidazole salt, applied in the field of pharmaceutical preparation, can solve the problems such as incomplete N alkylation reaction, unsatisfactory biimidazole yield and purity, difficulty in purifying telmisartan, etc. Simple operation, reducing the amount of reaction base, suitable for large-scale production

Active Publication Date: 2010-05-12
滨海三甬药业化学有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Wherein 2-n-propyl-4 methyl-6-(methylbenzimidazol-2-yl) benzimidazole is the intermediate for preparing telmisartan, (but there are some defects with this as the synthetic technique of intermediate , the yield and the purity are not ideal when biimidazole is synthesized in the original process, and the N alkylation reaction in the next step is not complete enough, resulting in the difficulty of purifying telmisartan), 2-n-propyl-4 methyl-6-(methyl Benzimidazol-2-yl) benzimidazole salt can replace the original 2-n-propyl-4 methyl-6-(methylbenzimidazol-2-yl) benzimidazole to carry out telmisartan synthesis, and also It is beneficial to the next N-alkylation reaction, and does not affect the synthesis and quality of telmisartan

Method used

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  • 2-propyl-4 methyl-6-(tolimidazole-2group) benzoglioxaline salt and method for producing the same
  • 2-propyl-4 methyl-6-(tolimidazole-2group) benzoglioxaline salt and method for producing the same

Examples

Experimental program
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Effect test

example 1

[0023] 1. Add 100g of PPA, 21.8g (0.1mol) of 2-n-propyl-4-methyl-6-carboxybenzimidazole and 21.5g of N-methyl-o-phenylenediamine into the reaction flask, feed the material under the protection of N2, and heat To 100°C-160°C, react for 8-20 hours, lower to 70-80°C, add 200ml of water to the reaction, adjust PH=1~2 with hydrochloric acid, put in 5-8% activated carbon, filter at 80°C for 5-10 minutes , Repeated reaction, adjust the pH to 12-14 with NaOH, react for several hours, filter to get the intermediate crude product 2-n-propyl-4-methyl-6-(methylbenzimidazol-2-yl)benzimidazole sodium salt.

[0024] 2. Dissolve the crude 2-n-propyl-4-methyl-6-(methylbenzimidazol-2-yl) benzimidazole sodium salt crude product from the previous step in 200 ml of ethanol, heat to dissolve, cool to room temperature, 400 ml of 1N NaOH was added, and the compound 2-n-propyl-4methyl-6-(methylbenzimidazol-2-yl)benzimidazole sodium salt was precipitated. 50-80 ℃ vacuum drying.

[0025] 3. Put 2-n-p...

example 2

[0026] Example 2 prepares Telmisartan

[0027] 1. Add 100gPPA, 21.8g (0.1) 2-n-propyl-4-methyl-6-carboxybenzimidazole and 21.5gN-methyl-o-phenylenediamine into the reaction flask, feed under N2 protection, and heat to 100 ℃-160℃, react for 8-20 hours, lower to 70-80℃, add 200ml of water to the reaction, adjust PH=1~2 with hydrochloric acid, put in 5-8% activated carbon, filter at 80℃ for 5-10 minutes, repeat For the reaction, adjust the pH to 12-14 with KOH, react for several hours, and filter to obtain the crude intermediate product 2-n-propyl-4methyl-6-(methylbenzimidazol-2-yl)benzimidazole potassium salt .

[0028] 2. Put the crude product of 2-n-propyl-4methyl-6-(methylbenzimidazol-2-yl) benzimidazole potassium salt from the previous step into 200 ml of ethanol, heat to dissolve, cool to room temperature, add With 400 ml of 1N KOH, the compound 2-n-propyl-4methyl-6-(methylbenzimidazol-2-yl)benzimidazole potassium salt was precipitated. 50-80 ℃ vacuum drying.

[0029] 3...

example 3

[0032]1. Add 100gPPA, 21.8g (0.1) 2-n-propyl-4-methyl-6-carboxybenzimidazole and 21.5gN-methyl-o-phenylenediamine into the reaction flask, feed under N2 protection, and heat to 100 ℃-160℃, react for 8-20 hours, drop to 70-80℃, add 200ml of water to the reaction, adjust pH=1~2 with hydrochloric acid, put in 5-8% activated carbon, filter at 80℃ for 5-10 minutes, repeat For the reaction, adjust the pH to 12-14 with NaOH, react for several hours, and filter to obtain the crude intermediate product 2-n-propyl-4methyl-6-(methylbenzimidazol-2-yl)benzimidazole sodium salt .

[0033] 2. Put the crude 2-n-propyl-4methyl-6-(methylbenzimidazol-2-yl) benzimidazole sodium salt crude product from the previous step into 200 ml of isopropanol, heat to dissolve, and add activated carbon 2 grams, filtered while hot, added 200 milliliters of water in the filtrate, cooled to room temperature, precipitated compound 2-n-propyl-4 methyl-6-(methylbenzimidazol-2-yl) benzimidazole, filtered, 80 Drying...

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Abstract

The invention relates to an intermediate 2-n-propyl-4 methyl-6-(methyl benzimidazole-2- radical) benzimidazole salt for high blood pressure resistance medicine that is telmisartan and the preparationmethod thereof. The intermediate has no any reports in the literature. The invention has the advantages of easy control of the preparation reaction condition, easy getting of raw material, and being suitable for mass production. The intermediate can be used for preparing the telmisartan.

Description

technical field [0001] The invention relates to the technical field of medicine preparation, in particular to an intermediate 2-n-propyl-4methyl-6-(methylbenzimidazol-2-yl)benzimidazole salt for preparing telmisartan and a preparation method thereof. Background technique: [0002] With the research of medical technology against hypertension, a new generation of antihypertensive drugs has gradually come out and is widely used clinically. Non-peptide angiotensin II receptor inhibitors, that is, sartan drugs, have become a new generation of antihypertensive drugs. These drugs have excellent curative effect and good tolerance, and are highly effective in the treatment of primary and secondary hypertension. Blood pressure, and congestive heart failure have better results. The preparation of sartan drugs has also become a concern. Telmisartan is a kind of sartan drug, which has the advantages of high bioavailability and long half-life. There are many reports in the literature a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D235/06
Inventor 屠勇军黄正良程荣德
Owner 滨海三甬药业化学有限公司