Method for preparing cefodizime sodium

A technology of cefodizime sodium and compounds, applied in the field of drug synthesis, can solve the problems of high cost, low yield, complicated operation, etc., and achieve the effect of low cost, high yield and simple operation

Active Publication Date: 2010-07-14
QILU ANTIBIOTICS PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] Compound 7-amino-3-(5-carboxymethyl-4-methyl-1.3-thiazole-2-mercaptomethyl) cef-2-ene-2-carboxylic acid (IV) generated in route C needs to use Purification of macroporous resin, complicated operation and high cost; in route D, the reaction of cefotaxime acid and MMTA at high temperature has poor color and low yield, which increases the production cost
The post-processing work of these two routes is relatively cumbersome and the yield is low

Method used

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  • Method for preparing cefodizime sodium
  • Method for preparing cefodizime sodium
  • Method for preparing cefodizime sodium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] [Example 1] Synthesis of 7-amino-3-(5-carboxymethyl-4-methyl-1.3-thiazole-2-mercaptomethyl)cephalosporin-2-ene-2-carboxylic acid (IV)

[0035] Suspend 25g of the compound of formula (II) and 20g of the compound of formula (III) in 100ml of acetonitrile, add 250ml of boron trifluoride acetonitrile, stir at room temperature for 1hr, cool with ice water, add 300ml of water, and adjust the pH to 3.0 with ammonia. The crystals were cultivated for 1 hr, filtered with suction, and the filter cake was washed with 50 ml of water and 50 ml of acetone respectively, and dried under vacuum to obtain 26.7 g (yield 72.4%, purity 98.5%) of the compound of formula (IV).

Embodiment 2

[0036] [Example 2] Synthesis of 7-amino-3-(5-carboxymethyl-4-methyl-1.3-thiazole-2-mercaptomethyl)cephem-2-ene-2-carboxylic acid (IV)

[0037] Suspend 25g of the compound of formula (II) and 20g of the compound of formula (III) in 100ml of ethyl chloroacetate, pass in 19.5g of boron trifluoride gas, stir at room temperature for 1hr, cool down with ice water, add 200ml of water, ammonia The pH was adjusted to 2.8, the crystals were grown for 1 hr, and then filtered with suction. The filter cake was washed with 50 ml of water and 50 ml of acetone, and dried under vacuum to obtain 27.5 g (yield 73.3%, purity 98.2%) of the compound of formula (IV).

Embodiment 3

[0038] [Example 3] (6R, 7R)-7-[(2-amino-4-thiazolyl)-(methoxyimino)acetamido]-3-[[(5-carboxymethyl-4-methyl Synthesis of 2-thiazolyl)thio]methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2carboxylic acid (VI)

[0039] Suspend 26g of the compound of formula (IV) and 25g of the compound of formula (V) in 250ml of dichloromethane and 20ml of methanol, cool with ice water, add 18ml of triethylamine, react at the same temperature for 3hr, add 200ml of water for extraction, separate the water Layer, add 2g activated carbon to decolorize, filter, add 3N HCl to the filtrate to adjust the pH to 2.8, grow crystals for 1hr, filter with suction, and wash the filter cake with 100ml water and 50ml methanol respectively. It was vacuum dried to obtain 35.5 g (yield 93.9%, purity 98.3%) of the compound of formula (VI).

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Abstract

The invention relates to preparation of a cefodizime sodium. The preparation includes reacting compound of formula (II) and compound of formula (III) in presence of acid catalyst to obtain compound of formula (IN); acidylating compound of formula (IN) and compound of formula (V) to obtain compound of formula (VI) in mixed solution; generating compound of formula (I) by compound of formula (VI) inpresence of salt forming agents in mixed solution. The invention is easy to operate, high in yield, and low in cost.

Description

Technical field [0001] The invention relates to a method for preparing cephalosporin antibacterial drugs, in particular to a method for preparing cefodizime sodium, and belongs to the technical field of drug synthesis. Background technique [0002] Cefodizime sodium is a third-generation cephalosporin antibacterial drug, its chemical name is (6R, 7R)-7-[(2-amino-4-thiazolyl)-(methoxyimino)acetamido]- 3-[[(5-carboxymethyl-4-methyl-2-thiazolyl)thio]methyl]-8-oxo-5-thia-1-azabicyclo(4.2.0)octane-2 -Ene-2 carboxylic acid disodium salt (I), the chemical structure is as follows: [0003] [0004] The drug was developed by the German company Hoechst. Due to its duality of antibacterial and immune regulation, it has been widely used in clinical practice. [0005] At present, cefodizime sodium (I) is mainly prepared from cefodizime acid (VI), and the most important thing in the preparation process is the dissolution of cefodizime acid (VI). [0006] U.S. Patent No. 5,126,445 discloses route ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D501/36A61K31/546A61P31/04
Inventor 李凤侠范美菊王勇进
Owner QILU ANTIBIOTICS PHARMA
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