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

"One-pot" synthesis of irbesartan intermediate

A technology for intermediates and compounds, applied in the field of antihypertensive drugs, can solve problems such as unfavorable industrial production, and achieve the effects of convenient operation, high yield and low cost

Inactive Publication Date: 2011-12-21
河南华商药业有限公司
View PDF2 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Chinese patent CN1429817[2003.7.16] has reported the production technology that above-mentioned technical process is improved, and cyclopentanone obtains 1-amino cyclopentanecyanide through addition reaction, and this The cyanide is improved to be hydrolyzed under alkaline conditions to obtain the compound amidoamide (II), and the compound amidoamide (II) is not separated and subjected to valerylation to obtain the compound diamide (III), but it needs to be cooled to -12 The low temperature below ℃ is not conducive to industrial production, and the compound diamide (III) needs to be separated and purified, and then cyclized under alkaline conditions to obtain the spiroheterocycle (IV)

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
  • "One-pot" synthesis of irbesartan intermediate
  • "One-pot" synthesis of irbesartan intermediate
  • "One-pot" synthesis of irbesartan intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Example 1: 20g sodium cyanide (0.41mol) is dissolved in 40mL water, add 60mL aqueous solution containing 23g ammonium chloride (0.43mol), 35mL ammonia water and 40mL methanol solution containing 30g cyclopentanone (0.36mol), stir at room temperature After 1.5h, the temperature was raised to 60°C and stirred for another 45min, then the heating was stopped, and the stirring was continued for 45min. Cool to 25°C, extract with dichloromethane (80ml×6), combine organic phases, dry over anhydrous magnesium sulfate, and filter to obtain a dichloromethane solution containing 39g of 1-aminocyclopentanylcyanide (1). Add 39g (0.385mol) of triethylamine to the above solution, cool to 20°C, add 42g (0.348mol) of n-valeryl chloride dropwise, the temperature rises to 35°C and stir for 2 hours. , 80mL of 2% hydrochloric acid water and 100mL of water, distilled off dichloromethane to obtain about 63g of brown oil compound (2). Compound (2) was added to a solution of 200mL methanol and...

Embodiment 2

[0020] Embodiment 2: 20g sodium cyanide (0.41mol) is dissolved in 40mL water, add the 60mL aqueous solution that contains 23g ammonium chloride (0.43mol), 35mL ammoniacal liquor and the 40mL methanol solution that contains 30g cyclopentanone (0.36mol), stir at room temperature After 1.5h, the temperature was raised to 60°C and stirred for another 45min, then the heating was stopped, and the stirring was continued for 45min. Cool to 25°C, extract with toluene (80ml×6), combine organic phases, dry over anhydrous magnesium sulfate, and filter to obtain a toluene solution containing 39g of 1-aminocyclopentacyanide (1). Add 39g (0.385mol) of triethylamine to the above solution, cool to 20°C, add 42g (0.348mol) of n-valeryl chloride dropwise, the temperature rises to 50°C and stir for 2 hours. , 80mL of 2% hydrochloric acid water and 100mL of water, and vacuum evaporated toluene to obtain about 64g of brown oil compound (2). Add compound (2) to a solution of 200mL methanol and 80m...

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 relates to an improved synthesis process of an antihypertensive drug irbesartan intermediate 2-butyl-1,3-diazaspiro[4.4]nonane-1-en-4-one. Cyclopentanone undergoes an addition reaction to obtain 1-aminocyclopentyl cyanide. The cyanide is first acylated, then hydrolyzed and cyclized under alkaline conditions to obtain the product. The positive effect of the present invention is that the first hydrolysis, then acylation and cyclization reported in the prior art is improved to first acylation, then hydrolysis and cyclization, each step does not go through the separation process, and the "one pot method" is realized Production. The operation process is simplified, the product yield is improved, the product quality is guaranteed, the production cost is reduced, and it is more conducive to large-scale industrial production.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and specifically relates to the preparation of an antihypertensive drug irbesartan intermediate 2-butyl-1,3-diazaspiro[4.4]nonane-1-en-4-one method. Background technique [0002] 2-Butyl-1,3-diazaspiro[4.4]nonane-1-en-4-one, commonly known as spiroheterocycle, is mainly used in the synthesis of angiotensin II receptor antagonist irbesartan , is a key intermediate in the synthesis process of irbesartan. [0003] Bernhart. C. A., Perreaut P. M., Ferrari B. P. et al. in J. Med. Chem. [1993, 36(22): 3371-3380], Takenaka H., Hayase Y. in Heterocycles [1989, 29(6) : 1185-1189] and U.S. Patent USP5270317[1993.12.14], USP5559233[1996.7.24] the synthetic route of this spiroheterocyclic ring is mainly to obtain (reaction formula 1) through the following steps with cyclopentanone as starting material: [0004] Reaction 1 [0005] [0006] The starting material cyclopentanone is added...

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): C07D235/02
Inventor 夏玉良张建臣郭鑫博袁坤朋王景民夏文涛
Owner 河南华商药业有限公司
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