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A kind of preparation method of moxifloxacin hydrochloride

A technology of moxifloxacin hydrochloride and boric acid, applied in the field of preparation of moxifloxacin hydrochloride, can solve the problems of low yield, unsuitable for industrial production, complicated operation, etc., and achieve the effect of high yield

Inactive Publication Date: 2017-12-29
王润理 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The purpose of the present invention is to overcome the defects of low yield, complicated operation and unsuitable for industrialized production in the existing preparation method of moxifloxacin hydrochloride, and provide a kind of moxifloxacin hydrochloride which is simple, stable, suitable for industrial scale production and high yield. The preparation method of cifloxacin

Method used

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  • A kind of preparation method of moxifloxacin hydrochloride
  • A kind of preparation method of moxifloxacin hydrochloride

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] A preparation method for moxifloxacin hydrochloride, comprising the following steps:

[0032] Under nitrogen protection, 6.2g (100mmol) of boric acid (100mmol) and 35.7g (350mmol) of acetic anhydride were added to a three-necked flask and heated to 95°C for contact reaction for 1 hour, then cooled to 75°C; glycine (2.3g) was added and then 1-cyclo Propyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid ethyl ester 23.3g (72mmol), continue stirring at 75°C for 1.5 Hour, TLC monitors that reaction is complete, is cooled to room temperature, adds acetonitrile (86ml) and N-methylmorpholine 21.2g (210mmol), then with (S, S)-2,8-diazabicyclo[4.3.0] React 8.6g (68mmol) of nonane at 65°C for 1.5 hours, cool down to room temperature, filter out insoluble matter, add methanol (170ml), add concentrated hydrochloric acid dropwise at room temperature, adjust the pH value to 1.5, stir for 2 hours, then cool down to - Crystallize at 8°C, filter with suction, wash w...

Embodiment 2

[0034] A preparation method for moxifloxacin hydrochloride, comprising the following steps:

[0035]Under the protection of nitrogen, 6.2g (100mmol) of boric acid (100mmol) and 35.7g (350mmol) of acetic anhydride were added to a three-necked flask and heated to 85°C for contact reaction for 1 hour, then cooled to 75°C; glycine (2.6g) was added and then 1-cyclo Propyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid ethyl ester 21.7g (67mmol), continue stirring at 75°C for 2 Hour, TLC monitoring reaction is complete, is cooled to room temperature, adds acetonitrile 80ml (2 times of nonane weight) and N-methylmorpholine 23.8g (235mmol), then with (S, S)-2,8-diazepine Bicyclo[4.3.0]nonane 8.1g (64mmol) reacted at 60°C for 1 hour, cooled to room temperature, filtered off insoluble matter, added methanol (160ml), added dropwise concentrated hydrochloric acid at room temperature, adjusted the pH value to 1, and stirred After 2 hours, cool down to -5°C for crystal...

Embodiment 3

[0037] A preparation method for moxifloxacin hydrochloride, comprising the following steps:

[0038] Under the protection of argon, 6.2g (100mmol) of boric acid (100mmol) and 40.8g (400mmol) of acetic anhydride were added to a three-necked flask and heated to 90°C for contact reaction for 1 hour, then cooled to 80°C; glycine (1g) was added and then 1-cyclo Propyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid ethyl ester 20.4g (63mmol), continue stirring at 80°C for 1.5 Hour, TLC monitors that reaction is complete, is cooled to room temperature, adds acetonitrile (75ml) and N-methylmorpholine 16.2g (160mmol), then with (S, S)-2,8-diazabicyclo[4.3.0] React 7.3g (58mmol) of nonane at 70°C for 2 hours, cool down to room temperature, filter out insoluble matter, add methanol (150ml), add concentrated hydrochloric acid dropwise at room temperature, adjust the pH value to 3, stir for 2 hours, then cool down to - Crystallize at 10°C, filter with suction, wash wi...

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Abstract

The invention discloses a preparation method of moxifloxacin hydrochloride. The method includes the following steps of making boric acid and acetic anhydride make contact and react for 1 h at a temperature of 85-105 DEG C in protection gas, lowering the temperature to 75-80 DEG C, adding a stable promoter and 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid ethyl ester, continuing to conduct stirring for the reaction for 1.5-3 h at a temperature of 75-80 DEG C, conducting monitoring and tracking till the reaction ends, cooling to the room temperature, adding acetonitrile and organic amine to make the mixture react with (S,S)-2,8-diazabicyclo[4.3.0]nonane for 1-2 h at a temperature of 60-70 DEG C, cooling to the room temperature, adding methyl alcohol, dropwise adding concentrated hydrochloric acid at a temperature of 5-10 DEG C, adjusting the pH value to 1-3, conducting stirring for 2 h, cooling to a temperature of -10 DEG C to -5 DEG C, conducting crystallization and suction filtration, conducting washing through cold ethyl alcohol, conducting decompression drying, and obtaining moxifloxacin hydrochloride. The stable promoter is selected from one or more of glycine, serine and threonine. The method is high in yield, simple in operation and aftertreatment and suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a preparation method of moxifloxacin hydrochloride. Background technique [0002] Moxifloxacin hydrochloride, chemical name: 1-cyclopropyl-7-(S,S-2,8-diazabicyclo[4.3.0]nonan-8-yl)-6-fluoro -8-Methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid hydrochloride is a broad-spectrum and 8-methoxyfluoroquinolone antibacterial drug with antibacterial activity. It can effectively treat infections caused by a variety of bacteria, and shows good activity against Gram-positive bacteria and atypical pathogens. The specific structural formula is as follows: [0003] [0004] Researchers in this field have conducted extensive research on the methods of synthesizing moxifloxacin, but there are still many problems in these methods, which affect the large-scale production of moxifloxacin. [0005] EP0550903 discloses the use of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D471/04
CPCC07D471/04
Inventor 王润理陈勇徐艳
Owner 王润理