CN102351843A - Synthesis method of 2-methyl piperazine lomefloxacin - Google Patents
Synthesis method of 2-methyl piperazine lomefloxacin Download PDFInfo
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Abstract
The invention relates to the technical field of chemical synthesis, in particular to a synthesis method of 2-methyl piperazine lomefloxacin. A report for synthesizing the compound is not yet heard, and Chinese patent CN101659654A discloses a preparation method of the compound. At present, the 2-methyl piperazine lomefloxacin is prepared by simulating the preparation method. The preparation method can be completed by four steps, wherein two-step reaction is needed in removal of a chelate compound and a tert-butoxy carbonyl, and each step is completed for long time. The synthesis method comprises the following three steps of: preparing 1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid into a 1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic oxalic acid boron chelate compound, preparing a 1-ethyl-6,8-difluoro-7-(2-methyl-4-tert-butoxy carbonyl-1-piperazine)-1,4-dihydro-4-oxoquinoline-3-carboxylic oxalic acid boron chelate compound, and preparing a 1-ethyl-6,8-difluoro-7-(2-methyl-1-piperazine)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (a compound of the formula XI, the 2-methyl piperazine lomefloxacin).
Description
Technical field
The present invention relates to chemosynthesis technical field, specifically a kind of synthesis method of 2-methylpiperazine lomefloxacin.
Background technology
2-methylpiperazine lomefloxacin chemical name is a 1-ethyl-6; 8-two fluoro-7-(2-methyl isophthalic acid-piperazinyl)-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid (hereinafter to be referred as 2-methylpiperazine lomefloxacin) is one of major impurity of fluoroquinolones lomefloxacin hydrochloride.More little good more at its content of lomefloxacin hydrochloride, but definitely be not difficult to accomplish.Content for 2-methylpiperazine lomefloxacin in the objective evaluation lomefloxacin hydrochloride bulk drug; 2-methylpiperazine lomefloxacin reference substance must be arranged; In order to the lomefloxacin hydrochloride control test; To detect the amount of 2-methylpiperazine lomefloxacin in the lomefloxacin hydrochloride; Thereby judge the whether conformance with standard requirement of lomefloxacin hydrochloride quality, reduce in the medicine impurity to greatest extent the harm of human body.Therefore need the highly purified 2-methylpiperazine lomefloxacin of preparation.
But, there is not the report that synthesizes this compound so far, Chinese patent CN101659654A (open day is on March 3rd, 2010) discloses a kind of preparation method of chemical compounds I.Its structural formula is following:
Ra is for being rudimentary alkoxyl group in the formula, and Rb is selected from hydrogen, basic metal, alkaline-earth metal or its oxyhydroxide.
At present, all be that imitative its method prepares 2-methylpiperazine lomefloxacin.This preparation method needs four steps just can accomplish, and wherein take off huge legendary turtle compound and tertbutyloxycarbonyl and need two-step reaction, and per step all needs the long period to accomplish.
Summary of the invention
The object of the present invention is to provide a kind of synthesis method of 2-methylpiperazine lomefloxacin, this method is easy, synthesis step is few.
Technical scheme of the present invention is following:
A. the preparation of formula IX compound (being 1-ethyl-6,7,8-three fluoro-1,4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound):
With H
3The mixed solution of BO and glacial acetic acid is heated to 85～110 ℃, drips diacetyl oxide with 6～15ml/min speed, after dropwising, is warming up to 105～110 ℃, reacts 30～60 minutes, is cooled to below 80 ℃, with H
3BO
3The formula VIII compound that mole number is 0.48～0.8 times (1-ethyl-6,7,8-three fluoro-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid) adds, then 110～120 ℃ of reactions, 2～10 hours; No formula VIII compound (1-ethyl-6 to the TLC detection reaction liquid; 7,8-three fluoro-1,4-dihydro-4-Oxoquinoline-3-carboxylic acid) after; Reduce to 20～30 ℃; (350～400rpm) times adding frozen water 500～1500ml, it is muddy that solution becomes gradually, separates out solid for ice-water bath cooling and stirring fast.Suction filtration, water are washed till till pH5～6, and 25～40 ℃ of vacuum-dryings are to constant weight.Get formula IX compound (1-ethyl-6,7,8-three fluoro-1,4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound); Reaction formula is following:
B. the preparation of formula X compound (being 1-ethyl-6,8-two fluoro-7-(2-methyl-4-tertbutyloxycarbonyl-1-piperazinyl)-1,4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound):
At formula IX compound (1-ethyl-6; 7; 8-three fluoro-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound) and in the acetonitrile solution; Adding formula IX compound (1-ethyl-6; 7; 8-three fluoro-1,4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound) the formula IV compound (4-tertbutyloxycarbonyl-2-methylpiperazine) and the triethylamine of 1.5～2.0 times of mole numbers, reflux 12～24 hours; After TLC detects no formula IX compound; Reduce to room temperature, under the speed magnetic agitation of 250～350rpm, it is added in the entry; It is muddy that solution becomes gradually, separates out brown particle shape thing.Suction filtration; Water is washed till till pH5～6, to constant weight, obtains formula X compound (1-ethyl-6 in 25～40 ℃ of vacuum-dryings; 8-two fluoro-7-(2-methyl-4-tertbutyloxycarbonyl-1-piperazinyl)-1,4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound); Reaction formula is following:
C. formula XI compound is claimed the preparation of 2-methylpiperazine lomefloxacin (being 1-ethyl-6,8-two fluoro-7-(2-methyl isophthalic acid-piperazinyl)-1,4-dihydro-4-Oxoquinoline-3-carboxylic acid) again:
With formula X compound, 95% ethanol and water; At room temperature drip concentration 6mol/L hydrochloric acid with 6～15ml/min speed; Be heated to and refluxed 2～6 hours; To the no formula compound X of TLC detection; Remove ethanol under reduced pressure; After reducing to room temperature (20～30 ℃), suction filtration obtains 2-methylpiperazine lomefloxacin hydrochloride after the washing.With 5% (W/W) NaOH solution adjust pH to 10～11; Dissolve above-mentioned solids; Use the glacial acetic acid adjust pH to 5-6 again gained solution; Be cooled to 0 ℃～5 ℃, suction filtration gets 2-methylpiperazine lomefloxacin crude product, and water is given a baby a bath on the third day after its birth time; Till not having glacial acetic acid tart flavour; 95%V/V ethanol drip washing one time (being fast dry) promptly gets 2-methylpiperazine lomefloxacin (formula XI compound), the HPLC detection level.Reaction formula is following:
Further, the H described in the A step
3The mixed solution of BO and glacial acetic acid, the ml vol of glacial acetic acid are H
3BO
3100～160 times of mole number.
Further, the dropping diacetyl oxide described in the A step, the ml vol of dropping are H
3340～400 times of BO mole number.
Further, described in the B step in formula IX compound and acetonitrile solution, the ml vol of acetonitrile be formula IX compound mole number 250-1000 doubly.
Further, the triethylamine described in the B step, its ml vol are 300～500 times of formula IX compound mole number.
Further, the water described in the B step, its ml vol are 10000～15000 times of formula IX compound mole numbers.
Further, 95% ethanol described in the C step, its ml vol are 30000～60000 times of formula compound X mole number.
Further, the water described in the C step, its ml vol are 9000～18000 times of formula compound X mole number.
Further, the concentration 6mol/L hydrochloric acid described in the C step, the ml vol of its adding are 30000～60000 of formula compound X mole number.
The invention has the beneficial effects as follows:
1. with quinoline carboxylic acid's (1-ethyl-6; 7; 8-three fluoro-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid) be raw material; Rather than it is such with quinoline carboxylic ester (1-ethyl-6 by all documents; 7; 8-three fluoro-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid ethyl ester) is feedstock production huge legendary turtle compound (1-ethyl-6,7,8-three fluoro-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound); A kind of new method for preparing the huge legendary turtle compound is provided, and has eliminated the use of the very strong reagent of this toxicity of zinc chloride, reduced harm operator;
2. only need a step to accomplish by formula X compound 2-methylpiperazine lomefloxacin, and the reaction times shorten, reduced the use of methylene dichloride, ethyl acetate equal solvent, save the process of multistep precipitation and extraction.
Embodiment
Embodiment 1
The first step. formula IX compound is a 1-ethyl-6,7,8-three fluoro-1, the preparation of 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound:
Take into account and add boric acid 1.94g and acetate 4ml in the 100ml four-hole bottle of Drop-adding device in that mechanical stirring, spherical condensation tube, temperature are housed, stir down reacting by heating liquid to 90 ℃.Drip diacetyl oxide 11.5ml, drip with 6～15ml/min speed, 110 ℃ were reacted 30 minutes; Be cooled to below 80 ℃; Add 1-ethyl-6,7,8-three fluoro-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid (compound VIII) 6.78g (0.025mol); About 8 hours of reflux is reduced to room temperature after the no compound VIII in the TLC detection reaction liquid, and the ice-water bath cooling also adds frozen water 50ml under the stirring fast; Become muddy gradually, separate out solid.Suction filtration, water are washed till till the neutrality (pH5～6), and vacuum-drying is to constant weight below 40 ℃.
Second step. formula X compound is a 1-ethyl-6,8-two fluoro-7-(2-methyl-4-tertbutyloxycarbonyl-1-piperazinyl)-1, the preparation of 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound:
Mechanical stirring is being housed; Spherical condensation tube; Add 1-ethyl-6 in the 100ml four-hole bottle of thermometer; 7; 8-three fluoro-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound (being formula IX compound) 4.0g (0.20mol) and acetonitrile 50ml; Open stirring; Add 4-tertbutyloxycarbonyl-2-methylpiperazine (formula IV compound) 3.0g and triethylamine 4.0ml subsequently; Reflux 24 hours; Reduce to room temperature after the TLC detection reaction is complete; Under speed 250rpm magnetic agitation, it is slowly added in the beaker that fills 150ml water; Become muddy gradually, separate out brown particle shape solid.Suction filtration, water are washed till till the neutrality (pH5～6), and 40 ℃ of vacuum-dryings are to constant weight.
The 3rd. formula XI compound claims that again 2-methylpiperazine lomefloxacin is a 1-ethyl-6,8-two fluoro-7-(2-methyl isophthalic acid-piperazinyl)-1, the preparation of 4-dihydro-4-Oxoquinoline-3-carboxylic acid:
, the 100ml four-hole bottle of mechanical stirring, spherical condensation tube, thermometer adds 1-ethyl-6 in being housed; 8-two fluoro-7-(2-methyl-4-tertbutyloxycarbonyl-1-piperazinyl)-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound (compound X) 2.36g, 95% ethanol 60ml and water 20ml; Drip 6mol/L hydrochloric acid 30ml under the room temperature; Reflux removed ethanol under reduced pressure to reacting completely in about 4 hours, reduce to room temperature after; Filter, obtain 2-methylpiperazine lomefloxacin hydrochloride after the washing.With 5% (W/W) NaOH solution adjust pH to 11; Dissolve above-mentioned solids; Use the glacial acetic acid adjust pH to 5-6 again gained solution; Be cooled to 0 ℃～5 ℃; Suction filtration gets 2-methylpiperazine lomefloxacin crude product, and water is given a baby a bath on the third day after its birth time, ethanol drip washing one time; Obtain 2-methylpiperazine lomefloxacin elaboration, HPLC analyzes content and reaches more than 98.0%.
Embodiment 2
The first step. formula IX compound is a 1-ethyl-6,7,8-three fluoro-1, the preparation of 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound:
Take into account and add boric acid 19.4g and acetate 40ml in the 1000ml four-hole bottle of Drop-adding device in that mechanical stirring, spherical condensation tube, temperature are housed, stir down reacting by heating liquid to 90 ℃.Drip diacetyl oxide 120ml, drip with 6～15ml/min speed, 110 ℃ were reacted 30 minutes; Be cooled to below 60 ℃; Add 1-ethyl-6,7,8-three fluoro-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid (compound VIII) 67.8g (0.25mol); About 8 hours of reflux is reduced to room temperature behind the no formula VIII compound in the TLC detection reaction liquid, and the ice-water bath cooling also adds frozen water 600ml under the stirring fast; Become muddy gradually, separate out solid.Suction filtration, water are washed till till the neutrality (pH5～6), and vacuum-drying is to constant weight below 40 ℃.
Second step. formula X compound is a 1-ethyl-6,8-two fluoro-7-(2-methyl-4-tertbutyloxycarbonyl-1-piperazinyl)-1, the preparation of 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound:
Mechanical stirring is being housed; Spherical condensation tube; Add 1-ethyl-6 in the 500ml four-hole bottle of thermometer; 7; 8-three fluoro-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound (being the compound IX) 16g (0.04mol) and acetonitrile 200ml; Open stirring; Add 4-tertbutyloxycarbonyl-2-methylpiperazine (formula IV compound) 20g and triethylamine 16ml subsequently; Reflux 24 hours; Reduce to room temperature after the TLC detection reaction is complete; Under speed 300rpm magnetic agitation, it is slowly added in the beaker that fills 800ml water; Become muddy gradually, separate out brown particle shape solid.Suction filtration, water are washed till till the neutrality (pH5～6), and 40 ℃ of vacuum-dryings are to constant weight.
The 3rd. formula XI compound claims that again 2-methylpiperazine lomefloxacin is a 1-ethyl-6,8-two fluoro-7-(2-methyl isophthalic acid-piperazinyl)-1, the preparation of 4-dihydro-4-Oxoquinoline-3-carboxylic acid:
, the 5000ml four-hole bottle of mechanical stirring, spherical condensation tube, thermometer adds 1-ethyl-6 in being housed; 8-two fluoro-7-(2-methyl-4-tertbutyloxycarbonyl-1-piperazinyl)-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound (compound X) 7.8g, 95% ethanol 100ml and water 40ml; Drip 6mol/L hydrochloric acid 110ml under the room temperature; About 4 hours of reflux is to reacting completely; Remove ethanol under reduced pressure; After reducing to room temperature; Filter, obtain 2-methylpiperazine lomefloxacin hydrochloride after the washing.With 5% (W/W) NaOH solution adjust pH to 11; Dissolve above-mentioned solids; Use the glacial acetic acid adjust pH to 5-6 again gained solution; Be cooled to 0 ℃～5 ℃; Suction filtration gets 2-methylpiperazine lomefloxacin crude product, washes ethanol drip washing one time three times; Obtain 2-methylpiperazine lomefloxacin elaboration, HPLC analyzes content and reaches more than 98.0%.
Embodiment 3
The first step. formula IX compound is a 1-ethyl-6,7,8-three fluoro-1, the preparation of 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound:
Take into account and add boric acid 77.5g and acetate 160ml in the 3000ml four-hole bottle of Drop-adding device in that mechanical stirring, spherical condensation tube, temperature are housed, stir down reacting by heating liquid to 90 ℃.Drip diacetyl oxide 475ml, drip with 6～15ml/min speed, 110 ℃ were reacted 30 minutes; Be cooled to below 90 ℃; Add 1-ethyl-6,7,8-three fluoro-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid (compound VIII) 217g (0.80mol); About 8 hours of reflux is reduced to room temperature after the no compound VIII in the TLC detection reaction liquid, and the ice-water bath cooling also adds frozen water 1000ml under the stirring fast; Become muddy gradually, separate out solid.Suction filtration, water are washed till till the neutrality (pH5～6), and vacuum-drying is to constant weight below 40 ℃.
Second step. formula X compound is a 1-ethyl-6,8-two fluoro-7-(2-methyl-4-tertbutyloxycarbonyl-1-piperazinyl)-1, the preparation of 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound:
Mechanical stirring is being housed; Spherical condensation tube; Add 1-ethyl-6 in the 2000ml four-hole bottle of thermometer; 7; 8-three fluoro-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound (being the compound IX) 80g (0.40mol) and acetonitrile 1000ml; Open stirring; Add 4-tertbutyloxycarbonyl-2-methylpiperazine (formula IV compound) 80g and triethylamine 80ml subsequently; Reflux 24 hours; Reduce to room temperature after the TCL detection reaction is complete; Under speed 350rpm magnetic agitation, it is slowly added in the beaker that fills 3000ml water; Become muddy gradually, separate out brown particle shape solid.Suction filtration, water are washed till till the neutrality (pH5～6), and 40 ℃ of vacuum-dryings are to constant weight.
The 3rd. formula XI compound claims that again 2-methylpiperazine lomefloxacin is a 1-ethyl-6,8-two fluoro-7-(2-methyl isophthalic acid-piperazinyl)-1, the preparation of 4-dihydro-4-Oxoquinoline-3-carboxylic acid:
, the 5000ml four-hole bottle of mechanical stirring, spherical condensation tube, thermometer adds 1-ethyl-6 in being housed; 8-two fluoro-7-(2-methyl-4-tertbutyloxycarbonyl-1-piperazinyl)-1; 4-dihydro-4-Oxoquinoline-3-carboxylic acid oxalic acid boron huge legendary turtle compound (compound X) 118g, 95% ethanol 1500ml and water 450ml; Drip 6mol/L hydrochloric acid 1500ml under the room temperature; About 4 hours of reflux is to reacting completely; Remove ethanol under reduced pressure; After reducing to room temperature; Filter, obtain 2-methylpiperazine lomefloxacin hydrochloride after the washing.With 5% (W/W) NaOH solution adjust pH to 11; Dissolve above-mentioned solids; Use the glacial acetic acid adjust pH to 5-6 again gained solution; Be cooled to 0 ℃～5 ℃; Suction filtration gets 2-methylpiperazine lomefloxacin crude product, washes ethanol drip washing one time three times; Obtain 2-methylpiperazine lomefloxacin elaboration, HPLC analyzes content and reaches more than 98.0%.
Obviously, the above embodiment of the present invention only be for clearly the present invention is described and is done for example, and be not to be qualification to embodiment of the present invention.For the those of ordinary skill in affiliated field, on the basis of above-mentioned explanation, can also make other multi-form variation or change.Here can't give exhaustive to all embodiments.Everyly belong to the row that conspicuous variation that technical scheme of the present invention extends out or change still are in protection scope of the present invention.
Claims (9)
1. the synthesis method of a 2-methylpiperazine lomefloxacin is characterized in that may further comprise the steps:
The preparation of A, formula IX compound:
With H
3The mixed solution of BO and glacial acetic acid is heated to 85～110 ℃, drips diacetyl oxide with 6～15ml/min speed, after dropwising, is warming up to 105～110 ℃, reacts 30～60 minutes, is cooled to below 80 ℃, with H
3BO
3The formula VIII compound that mole number is 0.48～0.8 times adds; Then 110～120 ℃ of reactions 2～10 hours; To the TLC detection reaction liquid behind the no formula VIII compound; Reduce to 20～30 ℃; Ice-water bath cooling and under speed 350～400rpm stirs; Add frozen water 500～1500ml, it is muddy that solution becomes gradually, separates out solid; Suction filtration, water are washed till till pH5～6, and 25～40 ℃ of vacuum-dryings are to constant weight; Get formula IX compound; Reaction formula is following:
The preparation of B, formula X compound:
In formula IX compound and acetonitrile solution; Formula IV compound and triethylamine that adding formula IX compound mole number is 1.5～2.0 times; Reflux 12～24 hours; After TCL detects no formula IX compound; Reduce to room temperature, under the speed magnetic agitation of 250～350rpm, it is added in the entry; It is muddy that solution becomes gradually, separates out brown particle shape thing; Suction filtration, water are washed till till pH5～6, to constant weight, obtain formula X compound in 25～40 ℃ of vacuum-dryings; Reaction formula is following:
C, formula XI compound are claimed the preparation of 2-methylpiperazine lomefloxacin again:
With formula X compound, 95% ethanol and water, at room temperature drip concentration 6mol/L hydrochloric acid with 6～15ml/min speed, be heated to and refluxed 2～6 hours; After detecting no formula X compound to TLC, remove ethanol under reduced pressure, reduce to room temperature after; Suction filtration obtains 2-methylpiperazine lomefloxacin hydrochloride after the washing; With 5%NaOH solution adjust pH to 10～11, dissolve above-mentioned solids, use the glacial acetic acid adjust pH to 5-6 again gained solution, be cooled to 0 ℃～5 ℃, suction filtration gets 2-methylpiperazine lomefloxacin crude product, and water is given a baby a bath on the third day after its birth time, till not having glacial acetic acid tart flavour; 95%V/V ethanol drip washing one time, getting formula XI compound is 2-methylpiperazine lomefloxacin thing, the HPLC detection level; Reaction formula is following:
2. the synthesis method of a kind of 2-methylpiperazine lomefloxacin as claimed in claim 1 is characterized in that the H described in the A step
3The mixed solution of BO and glacial acetic acid, the ml vol of glacial acetic acid are H
3BO
3100～160 times of mole numbers.
3. the synthesis method of a kind of 2-methylpiperazine lomefloxacin as claimed in claim 1 is characterized in that the dropping diacetyl oxide described in the A step, and the ml vol of dropping is H
3340～400 times of BO mole number.
4. the synthesis method of a kind of 2-methylpiperazine lomefloxacin as claimed in claim 1, it is characterized in that described in the B step in formula IX compound and acetonitrile solution, the ml vol of acetonitrile be formula IX compound mole number 250-1000 doubly.
5. the synthesis method of a kind of 2-methylpiperazine lomefloxacin as claimed in claim 1 is characterized in that the triethylamine described in the B step, and its ml vol is 300～500 times of formula IX compound mole number.
6. the synthesis method of a kind of 2-methylpiperazine lomefloxacin as claimed in claim 1 is characterized in that the water described in the B step, and its ml vol is 10000～15000 times of formula IX compound mole numbers.
7. the synthesis method of a kind of 2-methylpiperazine lomefloxacin as claimed in claim 1 is characterized in that 95% ethanol described in the C step, and its ml vol is 30000～60000 times of formula compound X mole number.
8. the synthesis method of a kind of 2-methylpiperazine lomefloxacin as claimed in claim 1 is characterized in that the water described in the C step, and its ml vol is 9000～18000 times of formula compound X mole number.
9. the synthesis method of a kind of 2-methylpiperazine lomefloxacin as claimed in claim 1 is characterized in that the concentration 6mol/L hydrochloric acid described in the C step, and the ml vol of its adding is 30000～60000 of a formula compound X mole number.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114195760A (en) * | 2021-12-06 | 2022-03-18 | 江苏吉贝尔药业股份有限公司 | Lomefloxacin hydrochloride impurity and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005009970A1 (en) * | 2003-07-28 | 2005-02-03 | Matrix Laboratories Ltd | An improved process for the preparation of gatifloxacin |
| CN1616456A (en) * | 2004-09-28 | 2005-05-18 | 南京圣和药业有限公司 | Preparation of catifloxacin and purifying method |
| WO2005047260A1 (en) * | 2003-11-13 | 2005-05-26 | Quimica Sintetica, S.A. | Process for preparing gatifloxacin |
| CN101659654A (en) * | 2008-08-28 | 2010-03-03 | 四川科伦药物研究有限公司 | 2-Methylpiperazine fluoroquinolone compound and preparation method and application thereof |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005009970A1 (en) * | 2003-07-28 | 2005-02-03 | Matrix Laboratories Ltd | An improved process for the preparation of gatifloxacin |
| WO2005047260A1 (en) * | 2003-11-13 | 2005-05-26 | Quimica Sintetica, S.A. | Process for preparing gatifloxacin |
| CN1616456A (en) * | 2004-09-28 | 2005-05-18 | 南京圣和药业有限公司 | Preparation of catifloxacin and purifying method |
| CN101659654A (en) * | 2008-08-28 | 2010-03-03 | 四川科伦药物研究有限公司 | 2-Methylpiperazine fluoroquinolone compound and preparation method and application thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114195760A (en) * | 2021-12-06 | 2022-03-18 | 江苏吉贝尔药业股份有限公司 | Lomefloxacin hydrochloride impurity and preparation method thereof |
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