Improved method for preparing imidafenacin

A technology for compounds and substances, applied in the field of preparation of midanacin, can solve problems such as troublesome product purification, and achieve the effect of avoiding the use of a large amount of acid and alkali

Active Publication Date: 2012-10-24
BEIJING COLLAB PHARMA
View PDF5 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] This method uses a large amount of alkali, and the product purification is troublesome.

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
  • Improved method for preparing imidafenacin
  • Improved method for preparing imidafenacin
  • Improved method for preparing imidafenacin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] In a 50ml three-neck flask, add methanol 10ml, 4-(2-methylimidazol-1-yl)-2,2-diphenylbutyronitrile phosphate 2.0g (5mmol), DMSO1.17g (15mmol), at room temperature Add 1.7g of 30% hydrogen peroxide (the actual amount of hydrogen peroxide is 15mmol), under stirring, slowly add 5mol / L sodium hydroxide solution (about 5ml) dropwise, control the reaction temperature not to exceed 30°C, and raise the temperature to 50°C after adding, Stir for 3 hours, TLC shows that the reaction is complete (developing solvent: ethyl acetate), add 30ml of water, stir for 1h at an internal temperature below 15°C, filter, wash with water, and recrystallize the crude product with 90% ethanol (1g crude product is used 6ml solvent), to obtain about 1.21g of white powdery solid, yield 76%.

[0029] 1H NMR (CDCl3): δ2.228(3H, s), δ2.711(2H, t), δ3.787(2H, t), δ5.344(1H, brs), δ5.636(1H, brs), δ6.724(1H,s), δ6.850(1H,s), δ7.314-7.408(10H,m)

Embodiment 2

[0031] In a 50ml three-necked flask, add 10ml of ethanol, 2.0g (5mmol) of 4-(2-methylimidazol-1-yl)-2,2-diphenylbutyronitrile phosphate, 1.56g (20mmol) of DMSO, at room temperature Add 1.13g of 30% hydrogen peroxide (the actual amount of hydrogen peroxide is 10mmol), and slowly add 30% sodium carbonate solution (about 5ml) dropwise under stirring. hours, TLC shows that the reaction is complete (developing solvent: ethyl acetate), add 30ml of water, stir for 1h at an internal temperature below 15°C, filter, rinse with water, and recrystallize the obtained crude product with 90% ethanol (1g crude product with 6ml solvent ), about 1.15 g of white powdery solid was obtained, with a yield of 72%.

Embodiment 3

[0033] In a 50ml three-neck flask, add methanol 10ml, 4-(2-methylimidazol-1-yl)-2,2-diphenylbutyronitrile phosphate 2.0g (5mmol), DMSO1.17g (15mmol), at room temperature Add 2.26g of 30% hydrogen peroxide (the actual amount of hydrogen peroxide is 20mmol), under stirring, slowly add 5mol / L potassium hydroxide solution (about 5ml) dropwise, control the reaction temperature not to exceed 30°C, and raise the temperature to 40°C after adding, Stir for 2 hours, TLC shows that the reaction is complete (developing solvent: ethyl acetate), add 30ml of water, stir for 1h at an internal temperature below 15°C, filter, rinse with water, and recrystallize the obtained crude product with 90% ethanol (1g crude product is used 6ml solvent), to obtain about 1.19g of white powdery solid, yield 75%.

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 an improved method for preparing imidafenacin. The method is as follow: 4-(2-methyl-imidazol-1-yl)-2,2-diphenyl butyronitrile or phosphate of 4-(2-methyl-imidazol-1-yl)-2,2-diphenyl butyronitrile is reacted with peroxide by improved Radziszewski at the temperature of 40-60 DEG C in the presence of methanol and / or ethanol, dimethyl sulfoxide and alkali. The preparation method provided by the invention has high yield, large number of acid-base is avoided, and the method is a simple, economic and environment-friendly preparation method.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a preparation method of midanacin. Background technique [0002] Midanacin, the chemical name is 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide, and its structural formula is as shown in formula I: [0003] [0004] Midanacin is a new type of diphenylbutyramide anticholinergic drug jointly developed by Japan Ono Pharmaceutical Co., Ltd. and Kyorin Pharmaceutical Co., Ltd. It has high bladder selectivity and is used for the treatment of overactive bladder. It was launched in Japan in June 2007 . [0005] U.S. Patent No. 5,932,607 reports the preparation of midanacin. The method is to use 70% sulfuric acid at 140-150° C. to hydrolyze 4-(2-methylimidazol-1-yl)-2,2-diphenylbutyronitrile into Amide, after the reaction is completed, the excess sulfuric acid needs to be neutralized with alkali, and its reaction formula is as follows: [0006] [0007] The main disadvantage o...

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 Applications(China)
IPC IPC(8): C07D233/56
Inventor 段晓峰王宏志谈敦潮邹德超赵大龙王珂
Owner BEIJING COLLAB PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap