Preparation method for cephalosporin anti-infective drug

An anti-infection and cephalosporin technology, applied in the direction of organic chemistry, etc., can solve the problems of low yield of cefoxitone, unsuitable for large-scale industrial production, and high synthesis cost, and achieve easy operation of reaction conditions, good appearance and color, and production low cost effect

Active Publication Date: 2015-11-04
SHANDONG LUOXIN PARMACEUTICAL GROUP STOCK CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] This synthetic route is relatively short, but the productive rate of final cefazedone is on the low side, and its synthetic cost will increase accordingly, is not suitable for industrialized large-scale production

Method used

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  • Preparation method for cephalosporin anti-infective drug
  • Preparation method for cephalosporin anti-infective drug
  • Preparation method for cephalosporin anti-infective drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] 1) p-methoxybenzyl 7-phenylacetamido-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-3-cephem-4-carboxylate ( GTDE) preparation

[0030] Add 600mL acetone into the dry reaction vessel, heat to 50°C, add 102.5gGCLE (content 95%, technical grade, 0.2mol) into the acetone, stir to dissolve, add 29.1g 2-mercapto-5-methyl-1, 3,4-Thiadiazole (MMTD, 0.22mol), the reaction temperature is controlled at 50-55°C, and the reaction time is 2 hours. After the reaction is completed, add water to crystallize, filter with suction, wash with a small amount of water, and dry under vacuum below 40°C. 112.8 g GTDE (0.192 mol), yield 96%, HPLC purity 99.2%.

[0031] 2) Preparation of 7-amino-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (TDA)

[0032]Add 112.8g GTDE (0.192mol) and 225.6g p-cresol prepared in step 1) into the reaction kettle, control the temperature at 45-50°C, stir and react for 6 hours; cool to 40°C after the reaction is complete, and add 564g aceti...

Embodiment 2

[0038] 1) p-methoxybenzyl 7-phenylacetamido-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-3-cephem-4-carboxylate ( GTDE) preparation

[0039] Add 600mL acetone into the dry reaction vessel, heat to 50°C, add 198.2gGCLE (content 98.3%, technical grade, 0.4mol) into the acetone, stir to dissolve, add 63.5g 2-mercapto-5-methyl-1, 3,4-Thiadiazole (MMTD, 0.48mol), the reaction temperature is controlled at 50-55°C, and the reaction time is 3 hours. After the reaction is completed, add water to crystallize, filter with suction, wash with a small amount of water, and dry under vacuum below 40°C. 223.9 g GTDE (0.38 mol), yield 95%, HPLC purity 98.9%.

[0040] 2) Preparation of 7-amino-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (TDA)

[0041] Add 223.9g GTDE (0.38mol) and 2239g p-cresol prepared in step 1) into the reaction kettle, control the temperature at 45-50°C, stir and react for 1 hour; cool to 40°C after the reaction is complete, add 3360g ethyl ace...

Embodiment 3

[0047] 1) p-methoxybenzyl 7-phenylacetamido-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-3-cephem-4-carboxylate ( GTDE) preparation

[0048] Add 1000mL acetone into the dry reaction vessel, heat to 50°C, add 263gGCLE (content 92.5%, industrial grade, 0.5mol) into the acetone, stir to dissolve, add 76.02g 2-mercapto-5-methyl-1,3 , 4-Thiadiazole (MMTD, 0.575mol), the reaction temperature is controlled at 50-55°C, and the reaction time is 3 hours. After the reaction is completed, add water to crystallize, filter with suction, wash with a small amount of water, and dry under vacuum below 40°C to obtain 284.6 g GTDE (0.485 mol), yield 97%, HPLC purity 99.3%.

[0049] 2) Preparation of 7-amino-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (TDA)

[0050] Add 284.6g GTDE (0.485mol) and 1707.6g p-cresol prepared in step 1) into the reactor, control the temperature at 45-50°C, stir and react for 3 hours; cool to 40°C after the reaction is complete, and add 28...

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Abstract

The invention relates to a preparation method for a cephalosporin anti-infective drug-cefazedone sodium, belonging to the field of pharmaceutical synthesis. According to the invention, the method uses GCLE as a raw material to substitute 7-ACA and overcomes the defects of low yield, high pollution and the like in prior art; the preparation method with mild reaction conditions, little side reaction and simple process is provided; meanwhile, the method has the advantages of cheap and easily-available raw materials, low cost, high product yield, high product purity and applicability to industrial production.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a method for preparing cefzidone sodium, a cephalosporin anti-infective drug. Background technique [0002] Cefazedone sodium (cefazedone sodium) was developed by E Merck, Darmstadt laboratory in the late 1970s and is the first generation of cephalosporin antibiotics. In 1979, Merck was the first to go public in Germany, and then it was listed in neighboring countries, South Korea, Romania, Taiwan and other countries and regions. Cefozione sodium is a semi-synthetic cephalosporin antibiotic, which mainly inhibits and kills bacteria by interfering with and preventing the synthesis of bacterial cell walls. It has good antibacterial activity against common clinical Gram-positive and some Gram-negative bacteria, and some anaerobic bacteria, and can be used for respiratory system, urinary system, gastrointestinal tract infection, gynecology, peritoneum, skin, soft tissue and plastic sur...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/36C07D501/06C07D501/04C07D501/12
CPCC07D501/04C07D501/06C07D501/12C07D501/36
Inventor 王军左翠永高菲菲
Owner SHANDONG LUOXIN PARMACEUTICAL GROUP STOCK CO LTD
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