CN108033948A - A kind of preparation of De Lasha stars and its intermediate - Google Patents
A kind of preparation of De Lasha stars and its intermediate Download PDFInfo
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- CN108033948A CN108033948A CN201711463688.7A CN201711463688A CN108033948A CN 108033948 A CN108033948 A CN 108033948A CN 201711463688 A CN201711463688 A CN 201711463688A CN 108033948 A CN108033948 A CN 108033948A
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- GULIJBSAYSYMPP-CLFYSBASSA-N CCCOC(/C(/C(c(c(F)c1)cc(F)c1F)=O)=C\Nc(nc(c(F)c1)N)c1F)=O Chemical compound CCCOC(/C(/C(c(c(F)c1)cc(F)c1F)=O)=C\Nc(nc(c(F)c1)N)c1F)=O GULIJBSAYSYMPP-CLFYSBASSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
Abstract
A kind of preparation of De Lasha stars and its intermediate, the preparation method of the De Lasha stars, including by midbody compound, the purity of compound A 3 and compound W 4 are limited to ＞ 99.0%, the impurity compound of compound A 3 and compound W 4, compound 1 and the content of compound 2 are limited to less than 0.1%, are starting material with compound A 3 and compound W 4, are synthesized to obtain De Lasha stars according to the prior art.
Description
Technical field
The invention belongs to pharmaceutical technology field, the preparation of more particularly to a kind of De Lasha stars and its intermediate.
Background technology
De Lasha stars are wide spectrum fluoroquinolone antibiotics of new generation.This product is blue to leather compared with other quinoline ketone antiseptics
Family name's positive bacteria is more effective, particularly to the drug resistant methicillin-resistant staphylococcus aureus of other methods for quinolones antibacterial agents
(MRSA)。
De Lasha star chemistry is entitled：D-Glucose alcohol -1- deoxidation -1- methylaminos -, 1- (two fluoro- 2- pyrroles of 6- amino -3,5-
Piperidinyl) the fluoro- Isosorbide-5-Nitraes of the chloro- 6- of -8--dihydro -7- (3- hydroxyl -1- azelidinyls) -4- oxo -3- quinoline carboxylic acids, molecular weight is
635.97 structural formula is as follows：
U.S.'s Abbott Laboratories reaction scheme is document (WO2006015194)：
The reaction scheme of Japanese Yong Yong drugmakers is document (WO9711068)：
According to two lines, when the husky star (delafloxacin) of synthesis drawing obtains compound 7, one 0.1~0.2 is always had
Left and right impurity produces, and is ESI-MS according to LCMS the results shows molecular weight：[M+H]+684, thus it is speculated that impurity structure is compound 3,
3 structural formula of compound:
Through analyzing and researching, 3 source path of compound is as follows：
Two lines synthesize De Lasha stars (delafloxacin) in different ways, there is intermediate respectively in two lines
Compound A-3 and compound W-4；It is the important intermediate for synthesizing De Lasha stars (delafloxacin).
Impurity compound 1 and miscellaneous can be produced during above-mentioned two Compound Compound A-3 and compound W-4 is synthesized
Matter compound 2, compound 1 and 2 structural formula of compound are as follows：
Compound A-3 and compound W-4 are as important intermediate, and impurity compound therein 1 may proceed to compound 2
Reaction is participated in, impurity compound 3 is ultimately formed, so as to influence De Lasha stars (delafloxacin) bulk pharmaceutical chemicals quality.
We invent the conjunction of a kind of De Lasha stars (delafloxacin) intermediate impurities compound 1 and compound 2 for this
Into the purification process of method and analysis method, and intermediate.
The content of the invention
The present invention provides a kind of preparation method of De Lasha stars, and the described method includes by midbody compound, compound A-3
The impurity compound of ＞ 99.0%, compound A-3 and compound W-4 are limited to the purity of compound W-4, compound 1 is with changing
The content of compound 2 is limited to less than 0.1%, and the purity of gained De Lasha stars is higher than HPLC >=99.5%, and therein contaminated
Compound 3 does not detect.
The present invention has carried out the synthesis and analysis and research of De Lasha star intermediate impurities for this, there is provided the side solved the problems, such as
Method, can efficiently separate intermediate and impurity compound so that compound A-3 and compound W-4 purity ＞ 99.0%, it is contaminated
Compound 1 is less than 0.1% with compound 2, so as to improve De Lasha star bulk pharmaceutical chemicals quality.The present invention is real by the following technical programs
It is existing：
A kind of preparation method of De Lasha stars, the described method includes the purity of midbody compound A-3 is limited to ＞
The content of the impurity compound 1 of 99.0%, compound A-3 is limited to less than 0.1%, using compound A-3 as starting material according to
7 De Lasha stars of compound are prepared in following synthetic route
Or
The described method includes the purity of midbody compound W-4 is limited to ＞ 99.0%, the impurity chemical combination of compound W-4
The content of thing 2 is limited to less than 0.1%, using Compound Compound W-4 as starting material, is prepared according to following synthetic route
7 De Lasha stars of compound.
Preparation method of the present invention, the wherein preparation of compound A-3 and purification process, route are as follows：
Prepared by wherein compound A-3, carry out in organic solvent, organic solvent is selected from：Triethyl orthoformate, acetic anhydride,
Anhydrous formic acid, glacial acetic acid, toluene, acetonitrile, 1-methyl-2-pyrrolidinone, ethanol, ethyl acetate, water, 0~150 DEG C of reaction temperature.
Preferably wherein the purifying of compound A-3 is recrystallized using organic solvent, and the organic solvent is selected from：Methanol, ethanol, acetone,
Acetonitrile, tetrahydrofuran, isopropanol, water, 0~80 DEG C of reaction temperature；Most preferably, the weight that the purifying of wherein compound A-3 uses
Recrystallisation solvent is ethanol, and wherein ethanol consumption is 4~12 volumes times of compound A-3 weight, and 70~80 DEG C of reaction temperature, crystallizes
0~30 DEG C of temperature；When the crystallization time 0~3 is small；
Preparation method of the present invention, wherein the preparation of the compound W-4 and purification process, route are as follows：
Prepared by wherein compound W-4, reaction carries out in organic solvent, and organic solvent is selected from：Triethyl orthoformate, acetic acid
Acid anhydride, anhydrous formic acid, glacial acetic acid, toluene, acetonitrile, 1-methyl-2-pyrrolidinone, ethanol, ethyl acetate, water, reaction temperature 0~150
℃.Preferably, wherein compound W-4 purifying is recrystallized using organic solvent, and organic solvent is selected from methanol, ethanol, acetone, second
Nitrile, tetrahydrofuran, isopropanol, water, 0~80 DEG C of reaction temperature；Most preferably, the wherein purification process of compound W-4, use
Recrystallization solvent is ethanol, and wherein ethanol consumption is 4~12 volumes times of compound W-4 weight, and 70~80 DEG C of reaction temperature, is tied
Brilliant 0~30 DEG C of temperature；When the crystallization time 0~3 is small.
Preparation method of the present invention, wherein the preparation method of the impurity compound 1, route are as follows：
Reaction carries out in organic solvent, and organic solvent is selected from dichloromethane, ethyl acetate, triethyl orthoformate, acetic acid
Acid anhydride, anhydrous formic acid, glacial acetic acid, toluene, acetonitrile, 1-methyl-2-pyrrolidinone, ethanol, dimethyl sulfoxide (DMSO), n,N-Dimethylformamide,
N,N-dimethylacetamide, water, 0~150 DEG C of reaction temperature.
Preparation method of the present invention, wherein the preparation method of the impurity compound 2, route are as follows：
Reaction carries out in organic solvent, and organic solvent is selected from dichloromethane, ethyl acetate, acetic anhydride, primitive nail triethylenetetraminehexaacetic acid
Ester, acetic anhydride, anhydrous formic acid, glacial acetic acid, toluene, acetonitrile, 1-methyl-2-pyrrolidinone, ethanol, dimethyl sulfoxide (DMSO), N, N- dimethyl
Formamide, n,N-dimethylacetamide, water, 0~150 DEG C of reaction temperature.
The present invention further provides a kind of detection method of De Lasha stars, the method, step are as follows：
According to high performance liquid chromatography test, using octadecylsilane chemically bonded silica as filler (Thermo C184.6 ×
150mm, 5 μm) chromatographic column；Mobile phase A is 0.1% trifluoroacetic acid aqueous solution, and Mobile phase B is 0.1% trifluoroacetic acid acetonitrile；Press
Following table carries out gradient elution；Detection wavelength is 220nm；Flow velocity is 1.0ml per minute；Column temperature is 35 DEG C,
Using above chromatographic condition, according to HPLC methods using De Lasha stars bulk pharmaceutical chemicals as test sample, moral drawing can be detected
Midbody compound A-3 and compound W-4 in husky star bulk pharmaceutical chemicals；, and the content of impurity compound 1 and compound 2 and
The content of De Lasha stars.
It is described the present invention further provides a kind of De Lasha stars intermediate impurities compound 1 and the analysis method of compound 2
Method and step is as follows：
High performance liquid chromatography test, using octadecylsilane chemically bonded silica as filler (Thermo C18 4.6 ×
150mm, 5 μm) chromatographic column；Mobile phase A is 0.1% trifluoroacetic acid aqueous solution, and Mobile phase B is 0.1% trifluoroacetic acid acetonitrile；Press
Following table carries out gradient elution；Detection wavelength is 220nm；Flow velocity is 1.0ml per minute；Column temperature is 35 DEG C.
The intermediate impurities compound 1 and compound 2 in De Lasha star bulk pharmaceutical chemicals can be detected with above method.
The De Lasha stars being prepared with compound A-3 after purification, compound W-4 according to the prior art
(delafloxacin) bulk pharmaceutical chemicals, its Sino-German drawing sand star (delafloxacin) HPLC content >=99.5%, compound 3 are not examined
Go out.
Beneficial effects of the present invention
Synthesis and the analysis method of a kind of De Lasha stars intermediate impurities are provided in the present invention, is effectively synthesized contaminated
Compound 1 and compound 2, intermediate and impurity compound can be efficiently separated by providing analysis method, be obtained using means of purification
High-purity compound A-3 and compound W-4, purity purity ＞ 99.0%, impurity compound 1 are respectively less than 0.1% with compound 2.
Compound 3 is not detected by after the reaction was continued, improves De Lasha star bulk pharmaceutical chemicals purity.
Embodiment
The present invention is further illustrated by the following examples.
Embodiment 1
Prepare (2Z, 2'Z) -3,3'- ((3,5- difluoro pyridine -2,6- diyls) double (azane diyls)) double (2- (2,4,5- tri-
Fluoro benzoyl) ethyl acrylate) (compound 1)
(1) compound A-2 (5g, 20.3mmol), triethyl orthoformate (10ml), acetic anhydride (6ml) are mixed, risen
Temperature is to 120~130 DEG C, and when stirring 4 is small, system that the reaction was complete is cooled to 15~25 DEG C, adds acetonitrile (20ml), and water (3ml) stirs
Mix 10 minutes, be added dropwise to and fill 2,4- diaminourea -3,5- difluoro pyridine (1.2g, 8.1mmol), acetonitrile (20ml) it is anti-
Answer in bottle, be added dropwise be warming up to 60~70 DEG C stirring 10 it is small when.The reaction was complete, cools down, and filters, dry, obtains compound 1
4.0g, yield 75.1%.ESI-MS：[M+H]+658.
Embodiment 2
Prepare (2Z, 2'Z) -3,3'- ((3,5- difluoro pyridine -2,6- diyls) double (azane diyls)) it is double (2- (3- chloro- 2,
4,5- trifluoromethylbenzoyls) ethyl acrylate) (compound 2)
(1) compound W-2 (5g, 17.8mmol), triethyl orthoformate (10ml), acetic anhydride (6ml) are mixed, risen
Temperature is to 120~130 DEG C, and when stirring 4 is small, system that the reaction was complete is cooled to 15~25 DEG C, adds acetonitrile (20ml), and water (3ml) stirs
Mix 10 minutes, be added dropwise to and fill 2,4- diaminourea -3,5- difluoro pyridine (1.0g, 7.1mmol), acetonitrile (20ml) it is anti-
Answer in bottle, be added dropwise be warming up to 60~70 DEG C stirring 10 it is small when.The reaction was complete, cools down, and filters, dry, obtains compound 2
3.9g, yield 75.6%.ESI-MS：[M+H]+727.
Embodiment 3
Prepare 3- ((two fluoro- 2- pyridine radicals of 6- amino -3,5-) amino) -2- (2,4,5- trifluoromethylbenzoyls) acrylic acid second
Ester (compound A-3)
(1) compound A-2 (5g, 20.3mmol), triethyl orthoformate (10ml), acetic anhydride (6ml) are mixed, risen
Temperature is to 120~130 DEG C, and when stirring 4 is small, system that the reaction was complete is cooled to 15~25 DEG C, adds acetonitrile (20ml), and water (3ml) stirs
Mix 10 minutes, the mixed liquor for filling 2,4- diaminourea -3,5- difluoro pyridine (3.2g, 22.3mmol) and acetonitrile (20ml) be added dropwise,
It is added dropwise, when 10~30 DEG C of stirrings 1~2 of temperature control are small.The reaction was complete, and cooling, adds suitable quantity of water, filters, dry, obtains chemical combination
Thing A-3 7.5g, yield 92.0%.HPLC 94.6%, compound 1 4.7%.
(2) compound A-2 (5g, 20.3mmol), triethyl orthoformate (10ml), acetic anhydride (6ml) are mixed, risen
Temperature is to 120~130 DEG C, and when stirring 4 is small, system that the reaction was complete is cooled to 15~25 DEG C, adds, water (30ml), ethyl acetate
(30ml) is stirred 10 minutes, and liquid separation extraction, the drying of organic phase anhydrous sodium sulfate, is concentrated under reduced pressure, is dissolved with acetonitrile (20ml), is added dropwise
The mixed liquor of 2,4- diaminourea -3,5- difluoro pyridine (3.2g, 22.3mmol) and acetonitrile (20ml) is filled, is added dropwise, temperature control
When 10~30 DEG C of stirrings 1~2 are small.The reaction was complete, and cooling, adds suitable quantity of water, filters, dry, obtains compound A-3 7.9g,
HPLC 97.4%, compound 1 2.3%.Yield 97%.ESI-MS：[M+H]+402.1H NMR(400MHz,CDCl3)δ
11.33(d,1H),9.10(d,1H),7.44(td,1H),7.23(t,1H),7.15(t,1H),4.61(m,2H),4.14(q,
2H),1.15(s,3H).
Embodiment 4
3- ((two fluoro- 2- pyridine radicals of 6- amino -3,5-) amino) -2- (2,4,5- trifluoromethylbenzoyls) ethyl acrylate
(compound A-3) is purified
(1) by compound A-3 (10g, 24.9mmol)；Ethanol (80ml) is refluxed, and is cooled down, and is stirred, and is filtered, dry,
Obtain high-purity compound A-3 9.2g yields 92%.HPLC 99.6%, compound 1 0.07%.
Embodiment 5
Prepare 3- ((two fluoro- 2- pyridine radicals of 6- amino -3,5-) amino) -2- (the chloro- 2,4,5- trifluoromethylbenzoyls of 3-) third
Olefin(e) acid ethyl ester (compound W-4)
(1) compound W-2 (5g, 17.8mmol), triethyl orthoformate (8ml), acetic anhydride (6ml) are mixed, risen
Temperature is to 120~130 DEG C, and when stirring 4 is small, system that the reaction was complete is cooled to 15~25 DEG C, adds acetonitrile (20ml), and water (3ml) stirs
Mix 10 minutes, the mixed liquor for filling 2,4- diaminourea -3,5- difluoro pyridine (3.1g, 21.4mmol) and acetonitrile (20ml) be added dropwise,
It is added dropwise, when 10~30 DEG C of stirrings 1~2 of temperature control are small.The reaction was complete, and cooling, adds suitable quantity of water, filters, dry, obtains chemical combination
Thing W-4 7.1g, yield 91.5%.HPLC 94.0%, compound 2 4.6%.
(2) compound W-2 (5g, 17.8mmol), triethyl orthoformate (8ml), acetic anhydride (6ml) are mixed, risen
Temperature is to 120~130 DEG C, and when stirring 4 is small, system that the reaction was complete is cooled to 15~25 DEG C, adds, water (30ml), ethyl acetate
(30ml) is stirred 10 minutes, and liquid separation extraction, the drying of organic phase anhydrous sodium sulfate, is concentrated under reduced pressure, is dissolved with acetonitrile (20ml), is added dropwise
The mixed liquor of 2,4- diaminourea -3,5- difluoro pyridine (3.1g, 21.4mmol) and acetonitrile (20ml) is filled, is added dropwise, temperature control
When 10~30 DEG C of stirrings 1~2 are small.The reaction was complete, and cooling, adds suitable quantity of water, filters, dry, obtains compound W-4 7.3g,
HPLC 97.1%, compound 2 2.5%.Yield 94.1%.ESI-MS：[M+H]+436.1H NMR(400MHz,CDCl3)δ
11.31(d,1H),9.04(d,1H),7.41(td,1H),7.25(t,1H),4.65(m,2H),4.17(q,2H),1.11(s,
3H).
Embodiment 6
3- ((two fluoro- 2- pyridine radicals of 6- amino -3,5-) amino) -2- (the chloro- 2,4,5- trifluoromethylbenzoyls of 3-) acrylic acid
Ethyl ester (compound W-4) purifies
(1) by compound W-4 (10g, 22.9mmol)；Ethanol (80ml) is refluxed, and is cooled down, and is stirred, and is filtered, dry,
Obtain high-purity compound W-4 9.3g yields 93%.HPLC 99.7%, compound 20.06%.
Embodiment 7
A kind of preparation method of De Lasha stars, the described method includes by the midbody compound A-3's in above example
Purity is limited to ＞ 99.0%, and the content of the impurity compound 1 of compound A-3 is limited to less than 0.1%, using compound A-3 as
7 De Lasha stars of compound are prepared according to following synthetic route in starting material
It is not detected by compound 3
Embodiment 8
A kind of preparation method of De Lasha stars, the described method includes by the midbody compound W-4's in above example
Purity is limited to ＞ 99.0%, and the content of the impurity compound 2 of compound W-4 is limited to less than 0.1%, with Compound Compound
W-4 is starting material, and 7 De Lasha stars of compound are prepared according to following synthetic route.
It is not detected by compound 3
The invention is not limited in above-mentioned embodiment, those skilled in the art can also make a variety of changes accordingly,
But any scope that should all cover with equivalent or similar change of the invention in the claims in the present invention.
Claims (10)
1. a kind of preparation method of De Lasha stars, the described method includes the purity of midbody compound A-3 is limited to ＞
The content of the impurity compound 1 of 99.0%, compound A-3 is limited to less than 0.1%, using compound A-3 as starting material according to
7 De Lasha stars of compound are prepared in following synthetic route
Or
The described method includes the purity of midbody compound W-4 is limited to ＞ 99.0%, the impurity compound 2 of compound W-4
Content be limited to less than 0.1%, using Compound Compound W-4 as starting material, according to following being prepared of synthetic route
7 De Lasha stars of compound；
2. preparation method according to claim 1, the wherein preparation of compound A-3 and purification process, route are as follows：
Prepared by wherein compound A-3, carry out in organic solvent, organic solvent is selected from：Triethyl orthoformate, acetic anhydride are anhydrous
Formic acid, glacial acetic acid, toluene, acetonitrile, 1-methyl-2-pyrrolidinone, ethanol, ethyl acetate, water, 0~150 DEG C of reaction temperature.
3. preparation method according to claim 2, the wherein purifying of compound A-3 are recrystallized using organic solvent, described
Organic solvent is selected from：Methanol, ethanol, acetone, acetonitrile, tetrahydrofuran, isopropanol, water, 0~80 DEG C of reaction temperature.
4. the recrystallization solvent that the purifying of preparation method according to claim 3, wherein compound A-3 uses is ethanol,
Wherein ethanol consumption is 4~12 volumes times of compound A-3 weight, 70~80 DEG C of reaction temperature, 0~30 DEG C of crystallization temperature；Analysis
When brilliant time 0~3 is small.
5. preparation method according to claim 1, wherein the preparation of the compound W-4 and purification process, route are as follows：
Prepared by wherein compound W-4, reaction carries out in organic solvent, and organic solvent is selected from：Triethyl orthoformate, acetic anhydride,
Anhydrous formic acid, glacial acetic acid, toluene, acetonitrile, 1-methyl-2-pyrrolidinone, ethanol, ethyl acetate, water, 0~150 DEG C of reaction temperature.
6. the purifying of preparation method according to claim 5, wherein compound W-4 is recrystallized using organic solvent, You Jirong
Agent is selected from methanol, ethanol, acetone, acetonitrile, tetrahydrofuran, isopropanol, water, 0~80 DEG C of reaction temperature.
7. the purification process of preparation method according to claim 6, wherein compound W-4, the recrystallization solvent used for
Ethanol, wherein ethanol consumption are 4~12 volumes times of compound W-4 weight, 70~80 DEG C of reaction temperature, crystallization temperature 0~30
℃；When the crystallization time 0~3 is small.
8. preparation method according to claim 1, wherein the preparation method of the impurity compound 1, route are as follows：
Reaction carries out in organic solvent, and organic solvent is selected from dichloromethane, ethyl acetate, triethyl orthoformate, acetic anhydride, nothing
Water beetle acid, glacial acetic acid, toluene, acetonitrile, 1-methyl-2-pyrrolidinone, ethanol, dimethyl sulfoxide (DMSO), n,N-Dimethylformamide, N, N-
Dimethylacetylamide, water, 0~150 DEG C of reaction temperature.
9. preparation method according to claim 1, wherein the preparation method of the impurity compound 2, route are as follows：
Reaction carries out in organic solvent, and organic solvent is selected from dichloromethane, ethyl acetate, acetic anhydride, triethyl orthoformate, second
Acid anhydrides, anhydrous formic acid, glacial acetic acid, toluene, acetonitrile, 1-methyl-2-pyrrolidinone, ethanol, dimethyl sulfoxide (DMSO), N, N- dimethyl formyls
Amine, n,N-dimethylacetamide, water, 0~150 DEG C of reaction temperature.
10. a kind of detection method of De Lasha stars, the method, step are as follows：
According to high performance liquid chromatography test, using octadecylsilane chemically bonded silica as filler (Thermo C184.6 × 150mm,
5 μm) chromatographic column；Mobile phase A is 0.1% trifluoroacetic acid aqueous solution, and Mobile phase B is 0.1% trifluoroacetic acid acetonitrile；According to the form below into
Row gradient elution；Detection wavelength is 220nm；Flow velocity is 1.0ml per minute；Column temperature is 35 DEG C,
Using above chromatographic condition, according to HPLC methods using De Lasha stars bulk pharmaceutical chemicals as test sample, De Lasha stars can be detected
Midbody compound A-3 and compound W-4 in bulk pharmaceutical chemicals；, and impurity compound 1 and content and the moral drawing of compound 2
The content of Sha Xing.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113527262A (en) * | 2021-06-22 | 2021-10-22 | 安徽普利药业有限公司 | Refining method of delafloxacin and meglumine salt thereof |
| CN114031607A (en) * | 2021-11-16 | 2022-02-11 | 海南普利制药股份有限公司 | Refining method of delafloxacin and intermediate thereof |
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| DAVID M.: "Chlorination at the 8-position of a functionalized quinolone and the synthesis of quinolone antibiotic ABT-492", 《ORG. PROCESS. RES. DEV.》 * |
| 王小明: "新型喹诺酮类抗生素德拉沙星的合成研究", 《南京工业大学硕士论文》 * |
| 蔡明君等: "一种适合工业化生产的德拉沙星的合成方法", 《海峡药学》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113527262A (en) * | 2021-06-22 | 2021-10-22 | 安徽普利药业有限公司 | Refining method of delafloxacin and meglumine salt thereof |
| CN114031607A (en) * | 2021-11-16 | 2022-02-11 | 海南普利制药股份有限公司 | Refining method of delafloxacin and intermediate thereof |
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