Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of telmisartan intermediate and intermediate compound

A technology of telmisartan and compounds, which is applied in the preparation of telmisartan intermediates and the field of intermediate compounds, can solve the problems of low yield, long reaction steps, cumbersome operation, etc., and achieve high yield, cost reduction, The operation method is simple and convenient

Active Publication Date: 2013-01-16
联化科技(上海)有限公司 +1
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] The technical problem to be solved by this invention is in order to overcome the intermediate compound 2-n-propyl-4-methyl-6-(1-methyl-benzimidazol-2-yl) of existing preparation telmisartan In the preparation method of benzimidazole, the defects such as long reaction steps, cumbersome operation, and low yield provide a method for preparing an intermediate compound of telmisartan and an intermediate compound, and the preparation method of the present invention is easy to operate , the product is easy to purify, easy to scale up production, and can also achieve a relatively high yield

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of telmisartan intermediate and intermediate compound
  • Preparation method of telmisartan intermediate and intermediate compound
  • Preparation method of telmisartan intermediate and intermediate compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1 Preparation of N-methyl-N-(2-nitrophenyl)-N-(3-methyl-4-n-butyramide-5-nitrophenyl) formamide (compound 3)

[0034] 3-Methyl-4-n-butyramide-5-nitrobenzoic acid (21.2g, 0.08mol) was added into 600mL of dichloromethane and 100mL of thionyl chloride, heated and refluxed for 20h, and the intermediate obtained by concentration was dissolved directly without separation. In 100mL of DMF, add o-nitrobenzylamine (6.1g, 0.04mmol) into the reaction flask, stir at room temperature for 2d, add 500mL of dichloromethane, add dropwise 200mL of 2N sodium hydroxide solution, stir at room temperature for 1h, and separate , the aqueous layer was extracted with 200 mL of dichloromethane, the combined organic layers were washed with saturated brine, dried, filtered and concentrated to obtain a crude product that was recrystallized with ethyl acetate and petroleum ether to obtain 13.3 g of a light yellow powder with a yield of 83.1%.

[0035] H NMR (300MHz, CDCl 3 )δ: 8.23 ​​(br, 1...

Embodiment 2

[0037] Example 2 Preparation of N-methyl-N-(2-nitrophenyl)-N-(3-methyl-4-n-butyramide-5-nitrophenyl) formamide (compound 3)

[0038]3-Methyl-4-n-butyramide-5-nitrobenzoic acid (2.1g, 8mmol) was added to 100mL of dichloromethane and 10mL of thionyl chloride, heated and refluxed for 20h, and the intermediate obtained by concentration was directly dissolved in In 20mL of DMF, add o-nitrobenzylamine (1.2g, 8mmmol) into the reaction flask, stir at room temperature for 2d, add 50mL of dichloromethane, add dropwise 2N sodium hydroxide solution 40mL, stir at room temperature for 1h, separate liquid, water The layers were extracted with 500 mL of dichloromethane, the combined organic layers were washed with saturated brine, dried, filtered and concentrated to obtain a crude product that was separated by column chromatography to obtain 1.4 g of light yellow powder with a yield of 43.6%.

[0039] HPLC: 95.1% NMR data are the same as in Example 1.

Embodiment 3

[0040] Example 3 Preparation of N-methyl-N-(2-nitrophenyl)-N-(3-methyl-4-n-butyramide-5-nitrophenyl) formamide (compound 3)

[0041] Add 3-methyl-4-n-butyramide-5-nitrobenzoic acid (21.2g, 0.08mol) into 600mL of dichloromethane and 60mL of phosphorus trichloride, heat up and reflux for 20h, and concentrate the obtained intermediate directly into the solution without separation. In 100mL of DMF, add o-nitrobenzylamine (6.1g, 0.04mmol) into the reaction flask, stir at room temperature for 2d, add 500mL of dichloromethane, add dropwise 200mL of 2N sodium hydroxide solution, stir at room temperature for 1h, and separate , the aqueous layer was extracted with 200 mL of dichloromethane, the organic layers were combined and washed with saturated brine, dried, filtered and concentrated to obtain a crude product that was recrystallized with toluene and petroleum ether to obtain 10.1 g of a light yellow powder with a yield of 63.1%.

[0042] HPLC: 92.1% NMR data are the same as in Examp...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a preparation method of a telmisartan intermediate compound as shown in table 1, and is characterized in that the method comprises the following steps of performing a nitryl reduction reaction and a cyclization reaction of compound 3. The invention also discloses an intermediate for preparing compound 1. The preparation method of the invention has simple operations, has easily purified products, facilitates large-scale production, and achieves high yield.

Description

technical field [0001] The present invention specifically relates to a preparation method of an intermediate compound of telmisartan and an intermediate compound. Background technique [0002] Telmisartan intermediate, 2-n-propyl-4-methyl-6-(1-methyl-benzimidazol-2-yl)benzimidazole, English name 2-n-propyl-4-methyl -6-(1-methyl-benzamidazole-2-yl)benzamidazole, CAS is 152628-02-9, its structural formula is shown in formula 1. [0003] [0004] Compound 1 is an important intermediate for the preparation of telmisartan, and the intermediate obtained by nucleophilic substitution reaction with 4'-bromomethyl-2-bibenzoic acid tert-butyl is then removed under acidic conditions to obtain the tert-butyl group. Telmisartan is available (EP502314). However, as an important intermediate of telmisartan, its synthetic method has certain limitations. At present, several main synthetic routes of this intermediate are as follows: [0005] 1. The synthetic route reported in the literat...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D235/18C07C237/40
Inventor 王萍潘强彪李杨州邹本立
Owner 联化科技(上海)有限公司
Features
  • Generate Ideas
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com