A kind of method that non-palladium system prepares ertapenem

A technology of ertapenem and parent nucleus, which is applied in the field of preparation of ertapenem, can solve the problems of difficulty in completely removing heavy metal palladium residues, potential safety hazards, cumbersome post-processing and the like, and achieves high conversion rate, low raw material cost, The effect of high product purity

Inactive Publication Date: 2011-11-30
ZHEJIANG HISOAR PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this route is relatively mature, it has disadvantages such as high cost, high-pressure hydrogenolysis, potential safety hazards, difficulty in completely removing heavy metal palladium residues, and cumbersome post-treatment.

Method used

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  • A kind of method that non-palladium system prepares ertapenem
  • A kind of method that non-palladium system prepares ertapenem
  • A kind of method that non-palladium system prepares ertapenem

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Preparation of giertapenem with protection from the mother nucleus (with MAP as the mother nucleus)

[0028]

[0029] Add 700ml of nitrogen ethylpyrrolidone (NEP) into a reaction flask equipped with a low-temperature thermometer and mechanical stirring, lower the temperature of the system to 0°C under nitrogen purge, add 85g of penem mother nucleus MAP, stir until dissolved and clarified, then add unprotected 42g of ertapenem side chain II, after stirring for a while, lower the temperature of the reaction system to -50°C, keep the temperature constant, quickly add 56g of diisopropylamine to the reaction system, fully stir the reaction at this temperature for about 5 minutes, and slowly raise the temperature The reaction was continued at -15°C for 10 minutes (the reaction was monitored by HPLC until the side chain disappeared), and immediately put into the next step of reduction hydrolysis reaction.

[0030] Preparation of Ertapenem

[0031]

[0032] Add the a...

Embodiment 2

[0034] Preparation of giertapenem with protected core (with MPP as the core)

[0035]

[0036] Add 600ml of acetonitrile into a reaction flask equipped with a low-temperature thermometer and mechanical stirring, lower the system temperature to 0°C under nitrogen purging, add 70g of penem mother nucleus MPP, stir until dissolved and clarified, then add unprotected ertapenem side chain II 42g, after stirring for a while, lower the temperature of the reaction system to -50°C, keep the temperature constant, quickly add 47g of diisopropylamine to the reaction system, and fully stir the reaction at this temperature for about 1 hour (HPLC monitors the reaction until the side chain disappears), Immediately put into the next step of reduction hydrolysis reaction.

[0037] Preparation of Ertapenem

[0038]

[0039] Add the above solution into the reaction flask, then add 2.7L of phosphate buffer (pH=5.0), 420g of zinc powder, and stir vigorously at 25°C for 3 hours under the ...

Embodiment 3

[0041] Preparation of Mother Nucleus and Side Chain Band Protected Giertapenem (with MAP as Mother Nucleus)

[0042]

[0043] Add 600ml of dichloromethane into a reaction flask equipped with a low-temperature thermometer and mechanical stirring, lower the system temperature to 0°C under nitrogen purging, add 85g of penem mother nucleus MAP, stir until dissolved and clarified, then add carboxyl-protected Ertape South side chain II 51g, after stirring for a while, lower the temperature of the reaction system to -50°C, keep the temperature constant, quickly add 47g of diisopropylamine to the reaction system, fully stir the reaction at this temperature for about 2 hours (HPLC monitors the reaction until the side chain disappear), immediately put into the next reduction hydrolysis reaction.

[0044] Preparation of Ertapenem

[0045]

[0046]Add the above solution into the reaction bottle, then add 2.7L of phosphate buffer (pH=6.0), 580g of zinc powder, and stir vigorousl...

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Abstract

The invention discloses a method for preparing ertapenem in a non-palladium system. A docking reaction occurs under the action of ertapenem to generate protected ertapenem; 2) Add zinc powder as a reducing agent to remove the protecting group at pH=3.0-6.5; 3) Extract the ertapenem solution and crystallize to obtain Ertapenem. The method has relatively mild reaction conditions, is easy to operate, does not involve heavy metals in the whole process, and the product can be crystallized and separated out in post-treatment, with high purity.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry, and more specifically, relates to a preparation method of ertapenem. Background technique [0002] Penem drugs are known by medical experts as one of the most effective antibiotics with the strongest antibacterial activity and the widest antibacterial spectrum. Since the discovery of the first natural penem antibiotic--thiamycin in 1976, varieties with high clinical evaluation have emerged one after another. The penem drugs listed in the preparations, panipenem launched by Sankyo in Japan in 1994 is the second penem compound preparation, and meropenem launched by Japan's Sumitomo in 1994. These products have been highly evaluated in clinical applications . Such antibiotics not only have a broad antibacterial spectrum, such as strong antibacterial activity against Gram-positive bacteria and negative bacteria, aerobic bacteria, and anaerobic bacteria, but also are highly stable against ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D477/20C07D477/06
Inventor 钱广赵大同罗佳邱欢欢
Owner ZHEJIANG HISOAR PHARMA
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