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

Method for preparing Doripenem and important intermediate thereof

A technology of intermediates and compounds, applied in the field of preparation of doripenem, which can solve the problems of difficult product purification, difficult removal of aluminum ions, waste, etc.

Inactive Publication Date: 2009-09-16
北京上地新世纪生物医药研究所有限公司
View PDF1 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] There are many synthetic methods of doripenem, the main route is to use [4R-[4α, 5β, 6(R*)]]-4-nitrobenzyl-3-[(diphenylphosphino)oxy] -6-(1-Hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (also known as MAP) and side chain (2S, 4S)-1-tert-butoxycarbonyl-2-(N-tert-butoxycarbonyl-N-aminosulfonamido)methyl-4-mercaptopyrrolidine reacts to generate protected doripenem, and then uses three Aluminum chloride is deprotected to prepare doripenem (Chinese patent 92111069). The mercapto group in the side chain used in this route is not very stable, and generally needs to be made into forms such as hydrochloride or methanesulfonate, so that it needs to be prepared in the follow-up reaction. Add a large amount of organic base for neutralization, resulting in unnecessary waste and pressure on environmental protection; at the same time, after deprotection with aluminum trichloride, aluminum ions are difficult to remove from the system, and product purification is difficult

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
  • Method for preparing Doripenem and important intermediate thereof
  • Method for preparing Doripenem and important intermediate thereof
  • Method for preparing Doripenem and important intermediate thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Step 1, preparation of bis[(2S, 4S)-1-tert-butoxycarbonyl-2-hydroxymethyl-pyrrolidin-4 base]-disulfide:

[0021] In a 250ml three-necked flask, add (2S, 4S)-1-tert-butoxycarbonyl-2-hydroxymethyl-4-mercaptopyrrolidine crude product (CN92111069 Example 4, product of step 7) (6.93g, 30mmol) and Methanol (50ml) was stirred and dissolved, the temperature was lowered to below 0°C in an ice-salt bath, ferric chloride methanol solution (0.02g / 20ml) was added, and oxygen was passed through at 45°C for 10-15 hours for oxidation. The solid was precipitated by suction filtration, and was filtered and dried to obtain the product (4.8 g, yield 69%).

[0022] Step 2, preparation of bis[(2S,4S)-1-tert-butoxycarbonyl-2-(sulfonamidoamino)methyl-pyrrolidin-4 base]-disulfide:

[0023] In a dry 500ml three-necked flask, add the product from the previous step (4.6g, 0.01mol) and tetrahydrofuran (460ml), then add diethyl azodicarboxylate (DEAD) (3.31g), N-tert-butyl hydroxythio Amide (3g), ...

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 intermediate of pyrrolidine derivatives with a structure of formula (I). The invention also provides a method for preparing the compound of formula (I) and a method for preparing Doripenem by using the compound as raw material. The method for preparing the compound of formula (I) is simple, can adopt a way of one-pot for preparing the Doripenem, has low cost and simple and convenient operation, and is suitable for producing the Doripenem in large scale.

Description

technical field [0001] The invention belongs to the fields of organic chemistry and medicinal chemistry, and specifically relates to a new pyrrolidine derivative and a preparation method, as well as a method for preparing doripenem with it. Background technique [0002] Carbapenems are a class of broad-spectrum antibiotics, such drugs as imipenem and meropenem have been marketed. Doripenem (doripenem) is a pyrrolidine whose 2-position side chain is substituted with aminosulfonamide. It is a new broad-spectrum antibiotic of carbapenems developed by Shionogi Pharmaceutical Co., Ltd. of Japan. Most β-lactamases are stable in character. It is mainly used for abdominal infection, lower respiratory tract infection, gynecological infection, genitourinary tract infection, hip joint infection, skin and soft tissue infection, endocarditis, severe meningitis, sepsis and other severe infections, often when other anti-infective drugs are ineffective last line of defense. [0003] Ther...

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): C07D207/12C07D477/20
CPCY02P20/55
Inventor 张玉良李晶
Owner 北京上地新世纪生物医药研究所有限公司
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

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