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

Benzimidazole compound and preparation method thereof

A compound and mixed solution technology, applied in the direction of organic chemistry, can solve the problems of high price and high cost of ytterbium perfluorooctane sulfonate, and the need for improvement of telmisartan, and achieve low cost, easy operation, product purity and yield. high rate effect

Pending Publication Date: 2017-12-05
SUNSHINE LAKE PHARM CO LTD
View PDF2 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] In this method, the solvent perfluorodecalin and the rare earth metal catalyst ytterbium perfluorooctyl sulfonate are expensive, resulting in high cost of the entire route
[0015] The method for preparing telmisartan still needs to be improved at present

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
  • Benzimidazole compound and preparation method thereof
  • Benzimidazole compound and preparation method thereof
  • Benzimidazole compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] Example 1 Synthesis of N-(2-methyl-4-(1-methyl-1H-benzo[d]imidazol-2-yl)phenyl)butamidine (compound shown in formula (I))

[0083]

[0084] Will P 2 o 5 (4.5g, 31.5mmol) and MsOH (45.0g, 468mmol) were added to a 500mL reaction flask equipped with a magnet and a thermometer, and the reaction mixture was heated to 150°C. After the reaction solution became clear, n-butyramide (22g, 252mmol,) and 2-methyl-4-(1-methyl-1H-benzo[d]imidazol-2-yl)aniline (formula (II) indicated compound) (5 g, 21 mmol). After the reaction solution was stirred and reacted at 150°C for 21h, the reaction mixture was cooled to 60°C and 100mL of water was added. After the reaction solution was cooled to room temperature, 25mL of acetone was added to the reaction solution, and then the pH of the reaction solution was adjusted to Adjusted to 11-12, a large amount of solids were precipitated in the reaction solution, the reaction solution was stirred and reacted at room temperature for 5 hours, an...

Embodiment 2

[0086] Example 2 Synthesis of 1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-benzo[d]imidazole (compound represented by formula (Ⅲ))

[0087]

[0088] At room temperature (17°C), N-(2-methyl-4-(1-methyl-1H-benzo[d]imidazol-2-yl)phenyl)butamidine (5.33g, 17.40mmol, formula ( The compound shown in I)) and NaOH (2.78g, 69.58mmol) were suspended in acetonitrile (200mL), and NaClO aqueous solution (65.83g, 2.42wt%, 21.40mmol) was added to the reaction mixture. The reaction mixture was heated to 30° C. and stirred at constant temperature for 2.5 h. The reaction mixture was lowered to room temperature, and water (154mL) was added dropwise to the reaction mixture. After the addition of water, the reaction mixture was stirred at room temperature for 2h, filtered with suction, and the filter cake was washed with water (3×20mL) and placed in a vacuum oven at 60°C. Drying for 24h gave 1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-benzo[d]imidazole as a white solid (4.94g, yield: 93.30%, purity: 99.84 %) ...

Embodiment 3

[0090] Example 3 Synthesis of N-(2-methyl-4-(1-methyl-1H-benzo[d]imidazol-2-yl)phenyl)butamidine (compound shown in formula (I))

[0091] Will P 2 o 5 (0.9g, 6.3mmol) and MsOH (9.0g, 93.6mmol) were added to a 50mL reaction flask equipped with a magnet and a thermometer, and the reaction mixture was heated to 150°C. After the reaction solution becomes clear, add n-butyramide (according to the feeding ratio in the following table 1) and 2-methyl-4-(1-methyl-1H-benzo[d]imidazol-2-yl)aniline (formula Compound shown in (II)) (1.0 g, 4.2 mmol). After the reaction solution was stirred and reacted at 150° C. for 21 h, the reaction solution was sampled and sent for testing. The HPLC results are shown in Table 1.

[0092] It can be seen that when the molar ratio of the compound represented by the formula (II) to n-butyramide is 1:12, the content of the compound represented by the formula (I) in the reaction solution is the most, which further shows that the compound represented by the ...

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 benzimidazole compound and a preparation method thereof, and applications of the benzimidazole compound in preparation of telmisartan. According to the present invention, the prepared benzimidazole compound can be used for preparing telmisartan, and the preparation method has advantages of low raw material cost, simple operation, safety, controllability, high product purity and high total yield, and is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular, the invention relates to a benzimidazole compound and a preparation method thereof. Background technique [0002] Telmisartan is a new antihypertensive drug and a specific angiotensin II receptor (AT1 type) antagonist. Telmisartan substitutes for the angiotensin II receptor and binds with high affinity to the AT1 receptor subtype, the known site of action of angiotensin II. Telmisartan selectively binds to AT1 receptors, and the binding effect is long-lasting. It has the characteristics of stable blood pressure reduction and no coughing. [0003] Ries U.J. etc. use chlorobenzene as the reaction solvent, and 4-amino-3-methylbenzoic acid methyl ester (compound 2) reacts with n-butyryl chloride at 100 ° C to synthesize 4-butyrylamide-3-methylbenzoic acid methyl ester ( Compound 4); 4-butyrylamino-3-methylbenzoate (compound 4) in H 2 SO 4 (60%) at 0°C to synthesize 4-butyramide-...

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
IPC IPC(8): C07D235/18
CPCC07D235/18
Inventor 罗忠华罗勇峰肖毅漆春辉杨凤智蓝英
Owner SUNSHINE LAKE PHARM CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com