Synthesis method of biapenem ester

A technology for apenem ester and compound is applied in the field of synthesis of biapenem ester, can solve the problems of easy moisture absorption of compound, difficult preparation and storage, inconvenient preparation of biapenem ester, etc., and achieves the effect of easy operation

Active Publication Date: 2010-11-24
SHENZHEN HAIBIN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In the above reaction, compound (III) is very easy to absorb moisture, and it is not easy to prepare and store, thus bringing inconvenience to the preparation of biapenem

Method used

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  • Synthesis method of biapenem ester
  • Synthesis method of biapenem ester
  • Synthesis method of biapenem ester

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] In the case of air isolation, 500ml of tetrahydrofuran, 8.0g of compound (II) (X is Cl), 10.0g of (R is p-nitrobenzyl) compound (IV), 5.0g of tributylphosphine and 4.0g of Diisopropylethylamine was added to the reactor, reacted at room temperature for 6 hours, monitored by HPLC, the reaction was completed, adjusted to pH=4.7 with hydrochloric acid, cooled to -15°C, added 250ml of dichloromethane, stirred and crystallized for 5 hours, filtered, Wash with 100ml of dichloromethane and dry to obtain 8.1g of target product (I).

Embodiment 2

[0039] In the absence of air, mix 400ml of acetonitrile, 8.0g of compound (II) (X is Cl), 10.0g of (R is p-nitrobenzyl) compound (IV), 5.0g of tributylphosphine and 4.0g of Diisopropylethylamine was added to the reactor, reacted at room temperature for 6 hours, monitored by HPLC, the reaction was completed, adjusted to pH=3.5 with hydrochloric acid, cooled to -15°C, added 250ml of dichloromethane, stirred and crystallized for 5 hours, filtered, Wash with 100ml of dichloromethane and dry to obtain 9.1g of target product (I).

Embodiment 3

[0041] In the case of air isolation, 400ml of acetonitrile, 8.0g of compound (II) (X is Br), 10.0g of (R is p-nitrobenzyl) compound (IV), 5.0g of tributylphosphine and 4.0g of Diisopropylethylamine was added to the reactor, reacted at room temperature for 6 hours, monitored by HPLC, the reaction was completed, adjusted to pH=5.0 with hydrochloric acid, cooled to -25°C, added 250ml of dichloromethane, stirred and crystallized for 2 hours, filtered, Wash with 100ml of dichloromethane and dry to obtain 9.4g of target product (I).

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Abstract

The invention relates to a synthesis method of biapenem ester, which comprises the steps of: 1) under the condition of air isolation, adding organic solvent, compound (II), compound (IV), R13P and alkali into a reactor, controlling the reaction temperature, and reacting for more than 15min; 2) carrying out HPLC monitoring, and using acid to adjust a system to acidity after reaction; and 3) crystallizing, cooling the reaction liquid, adding crystallization solvent for stirring and crystallization, filtering and obtaining the target compound (compound I). The invention has simple and convenient operation, can directly crystallize without needing purification in the reaction, and avoids using biapenem branched chain which is compound (III) and is easy in moisture absorption and difficult to prepare and store.

Description

technical field [0001] The invention relates to a method for synthesizing 1β-methyl carbapenem antibiotic ester, in particular to a method for synthesizing biapenem ester. Background technique [0002] Biapenem is a new type of 1β-methyl carbapenem antibiotic developed by Lederle Company of Japan, which was approved for marketing in Japan in March 2002. Like meropenem, it has the characteristics of broad antibacterial spectrum and strong antibacterial activity. Compared with other marketed carbapenems, biapenem has almost zero nephrotoxicity, can be administered alone, has no central nervous system toxicity, and does not induce seizures. Clinically, it is widely used in acute and chronic infections caused by gram-negative aerobic bacteria, gram-positive aerobic bacteria and anaerobic bacteria that are sensitive to apenem. In addition, biapenem has a good curative effect in the treatment of plastic surgery infection, gynecological infection and ear, nose and throat infectio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D519/06
Inventor 赵鹏任鹏苏昌明陈波
Owner SHENZHEN HAIBIN PHARMA
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