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Preparation method of moxifloxacin hydrochloride

A technology of moxifloxacin hydrochloride and organic acid is applied in the field of preparation of moxifloxacin hydrochloride, and can solve the problems of difficulty in product purification, increased synthesis steps, increased types and quantities of reagents, and the like

Inactive Publication Date: 2012-09-19
郭峰
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0020] Judging from the various routes of synthesizing moxifloxacin above, they all involve the structural analysis of two key intermediates, quinolinic acid and (S, S)-2,8-diazabicyclo[4.3.0]nonane. Modification, from the economical point of view of the synthetic route, has increased the steps of synthesis, the types and quantities of reagents used will inevitably increase, which will inevitably bring more difficulties to the purification of products, and the total yield of synthesis will inevitably decrease. For industrialization, It will inevitably put forward higher requirements for labor protection, safety, and environmental protection, and the pressure on production costs will inevitably increase

Method used

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  • Preparation method of moxifloxacin hydrochloride
  • Preparation method of moxifloxacin hydrochloride
  • Preparation method of moxifloxacin hydrochloride

Examples

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Effect test

Embodiment 1

[0030] 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl 】-The preparation of 4-oxo-3-quinoline carboxylic acid: add 50 grams (0.182 moles) 1-cyclopropyl-6,7-difluoro-8-methoxy-4 in the there-necked flask of 1000 milliliters -Oxo-1,4-dihydro-3-quinolinecarboxylic acid, 500 ml of N,N-dimethylformamide, dissolved under stirring, the above solution was cooled to 10 degrees Celsius, and 26 ml (0.204 mole) (S, S)-2,8-diazabicyclo【4.3.0】nonane, after adding, a large amount of solids were precipitated, under stirring, 18 grams (0.182 moles) of triethylamine was added and heated to 50 Celsius, and stirred at 40-50 Celsius for 8 hours, followed by thin-plate chromatography. After the reaction, add 100 ml of water and stir for 2 hours, filter, wash the filter cake with a small amount of water, and vacuum-dry at 70 Celsius to obtain 64 grams of solid powder .

Embodiment 2

[0032]1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl 】-The preparation of 4-oxo-3-quinoline carboxylic acid: add 50 grams (0.182 moles) 1-cyclopropyl-6,7-difluoro-8-methoxy-4 in the there-necked flask of 1000 milliliters -Oxo-1,4-dihydro-3-quinolinecarboxylic acid, 500 milliliters of dimethyl sulfoxide, dissolved under stirring, the above solution was cooled to 10 degrees Celsius, and 26 milliliters (0.204 moles) (S , S)-2,8-diazabicyclo【4.3.0】nonane, after the addition was completed, a large amount of solids were precipitated, under stirring, 14 grams (0.182 moles) of pyridine was added, heated to 50 degrees Celsius, and at 50- Stir at 60 degrees Celsius for 8 hours, thin-plate chromatography followed the reaction, after the reaction, add 100 milliliters of water and stir for 2 hours, filter, the filter cake is washed with a small amount of water, and vacuum-dried at 70 degrees Celsius to obtain 66 grams of solid powder.

Embodiment 3

[0034] 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl 】-The preparation of 4-oxo-3-quinoline carboxylic acid: add 50 grams (0.182 moles) 1-cyclopropyl-6,7-difluoro-8-methoxy-4 in the there-necked flask of 1000 milliliters -Oxo-1,4-dihydro-3-quinolinecarboxylic acid, 500 ml of N,N-dimethylformamide and dimethyl sulfoxide mixed solvent (volume ratio is 1:1), dissolved under stirring , the above solution was cooled to 10 degrees Celsius, and 26 milliliters (0.204 moles) of (S, S)-2,8-diazabicyclo[4.3.0]nonane were added under constant stirring. After adding, a large amount of solids were precipitated. Under stirring, add 23.5 grams (0.182 moles) of diisopropylethylamine, heat to 50 degrees Celsius, and stir at 55-65 degrees Celsius for 8 hours, thin-plate chromatography follows the reaction, after the reaction finishes, add 100 milliliters of water and stir for 2 hour, filtered, and the filter cake was washed with a small amount ...

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Abstract

The invention relates to a preparation method of moxifloxacin hydrochloride, which comprises the steps of: (a) in an organic solvent, carrying out condensation on 1-cyclopropyl-6, 7-difluoro-8-methoxy-4-oxo-1, 4-dihydro-3-quinoline carboxylic acid and (S, S)-2, 8-diazabicyclo (4. 3. 0) nonane under the catalysis of tertiary amine to produce 1-cyclopropyl-6-fluoro-1, 4- dihydro-8-methoxy-7-((4aS, 7aS) octahydro-6H-pyrrole (3, 4-b) pyridine-6-group)-4-oxo-3- quinoline carboxylic acid; (b) in an organic solvent, reacting1-cyclopropyl-6-fluoro-1, 4- dihydro-8-methoxy-7-((4aS, 7aS) octahydro-6H-pyrrole (3, 4-b) pyridine-6-group)-4-oxo-3-quinoline carboxylic acid with pure chiral organic acid to produce easily purified complex salt; and (c) reacting the complex salt with hydrochloric acid or hydrogen chloride gas in water solution of a water-soluble organic solvent to produce moxifloxacin hydrochloride of a certain crystal form. The method has the advantages that reaction route is simple, raw materials are cheap and easy to obtain, reaction conditions are mild and easy to control; therefore, the method is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of moxifloxacin hydrochloride, and the compound is used for treating acute sinus adenitis, acute exacerbation of chronic bronchitis, acquired pneumonia, skin infection and the like. Background technique [0002] Moxifloxacin (moxifloxacin, 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) is the fourth generation of fluoroquinolone antibacterial drugs, it has a broad-spectrum antibacterial effect, has been used as a chemotherapeutic agent for humans and animals, and can effectively It can treat infections caused by various bacteria and can also be used for antisepsis of materials. It consists of compound (S,S)-2,8-diazabicyclo[4.3.0]nonane and compound 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo- 1,4-dihydro-3-quinolinecarboxylic acid condensation generation. The structure is as follows: [0003] [0004] 1-cyclopropyl-6-fluoro-1...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04
Inventor 郭峰
Owner 郭峰
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