CN107778308A - Compound and preparation method thereof - Google Patents
Compound and preparation method thereof Download PDFInfo
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- CN107778308A CN107778308A CN201610735589.9A CN201610735589A CN107778308A CN 107778308 A CN107778308 A CN 107778308A CN 201610735589 A CN201610735589 A CN 201610735589A CN 107778308 A CN107778308 A CN 107778308A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
The present invention proposes a kind of compound and preparation method thereof, wherein, compound has structure shown in formula 1, using the compound as standard items or reference substance, can be efficiently used for carrying out quality control to MOXIFLOXACIN bulk drug and formulation products.
Description
Technical field
The present invention relates to medicinal chemistry art, and specifically, the present invention relates to compound and preparation method thereof.
Background technology
Moxifloxacin hydrochloride (Moxifloxacin Hydrochloride) is the of Bayer A.G (Bayer) exploitation
4 generation QNSs, its pharmacological action show that the medicine is shown to gram positive bacteria, gram-negative bacteria, anaerobism in vitro
Bacterium, acid fast bacteria, atypical microorganism such as mycoplasma, Chlamydia and Legionella have broad spectrum antibiotic activity, and the antibacterial with wide spectrum is lived
Property, for treating the adult with the upper respiratory tract and ALRI, 0.5% moxifloxacin hydrochloride eye drops can be used for controlling
Treat neonate's bacterial conjunctivitis.
But the quality evaluating method of current moxifloxacin hydrochloride medicine could be improved.
The content of the invention
It is contemplated that at least solves one of technical problem in correlation technique to a certain extent.Therefore, the present invention
One purpose is to propose compound and preparation method thereof described in a kind of formula 1.The compound can be efficiently used for MOXIFLOXACIN
The quality control of medicine, i.e., compound can be used as standard items shown in formula 2 or reference substance is used for MOXIFLOXACIN bulk drug and preparation produces
The quality control of product.
According to an aspect of the present invention, the present invention proposes a kind of compound, and the compound has to be tied shown in formula 1
Structure,
During the quality testing of MOXIFLOXACIN bulk drug and preparation is carried out, inventor has found MOXIFLOXACIN raw material and system
Contain 1 impurity in agent, its structure is determined through carefully studying, the impurity has structure shown in formula 1.Inventor point
Analysis, the generation of the impurity is in the building-up process of moxifloxacin hydrochloride, because of side chain (S, S) -2,8- diazabicyclos [4.3.0]
Nonane with selective difference during two fluorine substitution reactions on quinolone parent nucleus phenyl ring and it is caused, and then closed with MOXIFLOXACIN
Into being transferred to finished product.The impurity is the isomer of MOXIFLOXACIN, and being named as 1- cyclopropyl -6-, (S, S-2,8- diaza are double
Ring [4.3.0] nonane -8- bases) the fluoro- 8- methoxies -4- oxos -1,4- dihydros -3- quinoline carboxylic acids of -7-.
According to the second aspect of the invention, the invention also provides a kind of method for preparing compound indicated before, including：
(1) reaction is hydrolyzed in compound shown in formula 2, to obtain compound shown in formula 3；
(2) compound shown in compound shown in formula 3 and formula 4 is reacted, to obtain compound shown in formula 1,
Therefore, quality control of the compound for MOXIFLOXACIN bulk drug and preparation shown in the higher formula 1 of purity is prepared
Fixture is significant.
In addition, compound shown in formula 1 according to the above embodiment of the present invention can also have technology additional as follows
Feature：
In some embodiments of the invention, in step (1), compound shown in formula 2 is entered in hydrochloric acid and methanol solution
The row hydrolysis.
In some embodiments of the invention, in step (1), the hydrolysis is under conditions of 50-60 degrees Celsius
Carry out 14-16 hour completions.
In some embodiments of the invention, in step (1), the concentration of the hydrochloric acid is 36 volume %, the hydrochloric acid with
The volume ratio of the methanol is 10-20：100.
In some embodiments of the invention, in step (1), compound shown in formula 2 and the mass volume ratio of the hydrochloric acid
For 1g：2-10ml.
In some embodiments of the invention, in step (2), compound shown in compound shown in formula 3 and formula 4 be containing
Carried out in the organic solvent of alkali, the organic solvent is at least one of Isosorbide-5-Nitrae dioxane, DMF, acetonitrile.
In some embodiments of the invention, in step (2), it is triethylamine that the alkali, which is,.
In some embodiments of the invention, in step (2), compound shown in formula 3 is in 80- with compound shown in formula 4
React what 4-20 hours completed under 100 degrees Celsius.
In some embodiments of the invention, in step (2), the mass ratio of compound shown in formula 3 and compound shown in formula 4
For 0.7-1.3：1.
In some embodiments of the invention, in step (2), concentration of the triethylamine in the organic solvent is
0.1-0.3 volumes %.
Brief description of the drawings
Fig. 1 is the HPLC-MS figures of compound shown in formula 1 that preparation method according to embodiments of the present invention obtains.
Fig. 2 is compound shown in formula 1 that preparation method according to embodiments of the present invention obtains1H NMR scheme.
Fig. 3 is compound shown in formula 1 that preparation method according to embodiments of the present invention obtains13C-NMR schemes.
Fig. 4 be compound shown in formula 1 that preparation method according to embodiments of the present invention obtains HMBC (1H→13C) full figure.
Fig. 5 be compound shown in formula 1 that preparation method according to embodiments of the present invention obtains HMBC (1H→13C) full figure
Partial enlarged drawing.
Fig. 6 be compound shown in formula 1 that preparation method according to embodiments of the present invention obtains HMBC (1H→13C) full figure
Partial enlarged drawing.
Fig. 7 is the HSQC figures of compound shown in formula 1 that preparation method according to embodiments of the present invention obtains.
Embodiment
Embodiments of the invention are described below in detail, the example of the embodiment is shown in the drawings, wherein from beginning to end
Same or similar label represents same or similar element or the element with same or like function.Below with reference to attached
The embodiment of figure description is exemplary, it is intended to for explaining the present invention, and is not considered as limiting the invention.
The present invention is the following discovery based on inventor and completed：
Impurity of the drug is typically referred to present in medicine, chemical constitution and the inconsistent any composition of the medicine.In medicine
It can be lessened the curative effect containing impurity, influence the stability of medicine, some even to human health or produces other toxic side effects.
Therefore, relevant material is detected, control pharmaceutical purity is extremely important.Inventor to multiple batches of MOXIFLOXACIN medicine material medicine with
And during preparation carries out quality testing, find in each batch MOXIFLOXACIN medicine material and preparation all common containing one
It impurity, the analysis found that, determine the impurity for the compound shown in formula 1：
Compound
Thus, in the first aspect of the present invention, the present invention proposes a kind of compound.According to an embodiment of the invention, should
Compound has structural formula shown in formula 1：
Using the compound as standard items or reference substance, the matter of MOXIFLOXACIN bulk drug and preparation can be efficiently used for
Amount control.
According to an embodiment of the invention, compound shown in formula 1 is chemical entitled：1- cyclopropyl -6- (S, S-2,8- diazas
Bicyclic [4.3.0] nonane -8- bases) the fluoro- 8- methoxies -4- oxos -1,4- dihydros -3- quinoline carboxylic acids of -7-.According to the implementation of the present invention
Example, inventor have found that compound shown in formula 1 is prevalent in not as impurity in the progress quality testing of MOXIFLOXACIN medicine
In Xisha star bulk drug and its preparation.Verify that the compound is in MOXIFLOXACIN building-up process by structural confirmation and quality analysis
It is caused due to the selective difference in two fluorine substitution reactions on quinolone parent nucleus phenyl ring.Thus, it is possible to by the institute of formula 1
Show that compound carries out quality testing and quality control as standard items or reference substance to MOXIFLOXACIN medicine, may contain for controlling
There is the quality of the MOXIFLOXACIN medicine of the impurity.
The preparation method of compound
In order to which the compound shown in formula 1 is used to carry out quality testing, it is necessary to there is high-purity to MOXIFLOXACIN medicine
Compound be used as reference substance, for control may be containing the impurity MOXIFLOXACIN medicine quality.Therefore, the present invention's
Second aspect, the method that the present invention proposes compound shown in a kind of formula 1.
According to a particular embodiment of the invention, this method includes：
(1) reaction is hydrolyzed in compound shown in formula 2, to obtain compound shown in formula 3；
(2) compound shown in compound shown in formula 3 and formula 4 is reacted, to obtain compound shown in formula 1,
Compound shown in factor 1 is the process contaminants of moxifloxacin hydrochloride, therefore it is husky in Moses that the compound is prepared
There is very important meaning in star bulk drug and preparation research.There is the method for compound shown in above-mentioned formula 1 experiment to grasp
Make the height of compound purity shown in simple, workable, prepared formula 1.Chemical combination shown in the formula 1 being prepared using this method
Thing can as the reference substance of the impurity of the drug in moxifloxacin hydrochloride, and after demarcation can be used for moxifloxacin hydrochloride quality
Research.
According to a particular embodiment of the invention, chemical combination shown in the formula 1 of the specific embodiment of the invention is described below in detail
The method of thing.
S100：The hydrolysis of compound shown in formula 2
(1) reaction is hydrolyzed in compound shown in formula 2, to obtain compound shown in formula 3.According to the specific of the present invention
Embodiment, reaction equation are as follows：
According to a particular embodiment of the invention, compound shown in formula 2 is that the hydrolysis is carried out in hydrochloric acid and methanol solution
Reaction.It is possible thereby to effectively compound shown in formula 2 is hydrolyzed.And then improve reaction efficiency and shownization of formula 3
The yield of compound.
According to a particular embodiment of the invention, above-mentioned hydrochloric acid used can be the hydrochloric acid that concentration is 36 volume %, and should
Hydrochloric acid and the volume ratio of methanol usage amount are 10-20：100.And then it can be provided effectively for the hydrolysis of compound shown in formula 2
Reaction system, improve hydrolysis effect.
According to a particular embodiment of the invention, compound shown in formula 2 and the mass volume ratio of above-mentioned hydrochloric acid are 1g：2-
10ml.Inventor has found that, if hydrochloric acid dosage is too low, compounds substrate shown in formula 2 is fully converted to the time of product formula 3 significantly
Extend, because the reaction later stage is heterogeneous system, the precipitation of compound product shown in formula 3 is by chemical combination shown in wrapping portion substrate formula 2
Thing, cause compound ratio transformation shown in substrate formula 2 relatively low；, can be to product because reaction is alcohol-water system if hydrochloric acid dosage is excessive
Compound shown in formula 3 has larger dissolubility, and then causes the hydrolysis yield of the step relatively low.Therefore, inventor passes through a large amount of
Experiment, it is 1g that research, which finds to control the mass volume ratio of compound and hydrochloric acid shown in formula 2,：2-10ml, hydrolysis can be significantly improved
Reaction efficiency, improve compound yield shown in formula 3.
According to a particular embodiment of the invention, hydrolysis be under conditions of 50-60 degrees Celsius carry out 14-16 hours it is complete
Into.And then compound shown in formula 2 can be caused to be fully hydrolyzed, improve the yield of compound shown in formula 3.Inventor's discovery, such as
Fruit control hydrolysis is too low, and the compound hydrolysis of substrate formula 2 greatly prolongs for the time of the compound of product formula 3.Because system is reacted
Temperature is close to reflux temperature, therefore reaction temperature is close to the system upper limit.If the reaction time is too short, substrate formula 2 is changed in system
The conversion ratio of compound can be relatively low, and the reaction time is long, and the conversion ratio of the compound of substrate formula 2 has tended towards stability, because of the reaction time
Extend, the step process period will be caused to extend.Therefore, control above-mentioned hydrolysis condition can further improve hydrolysis efficiency and
The compound yield of formula 3.
According to a particular embodiment of the invention, above-mentioned steps (1) comprises the following steps that：
Reaction：Compound, 100mL absolute methanols shown in 10g formulas 2 are added in 250mL round-bottomed flasks, after stirring and evenly mixing again
The volume % of 10-20mL 36 hydrochloric acid is slowly added to, charging finishes；System is warming up to 50-60 DEG C, at this temperature stirring reaction 14-
16h；
Post processing：After reaction terminates, system is cooled to 10 DEG C, stirring and crystallizing 2h, and system decompression filtration, filter cake uses 20mL
Absolute methanol washs, and after being dried in vacuo 8-20h at 60-80 DEG C, obtains compound shown in formula 3, yield：83-97%；
S200：The compound shown in preparation of compounds of formula 1 shown in compound and formula 4 as shown in formula 3
(2) compound shown in compound shown in formula 3 and formula 4 is reacted, to obtain compound shown in formula 1.According to this hair
Bright specific embodiment, reaction equation are as follows：
According to a particular embodiment of the invention, compound shown in compound shown in formula 3 and formula 4 is organic molten containing alkali
Carried out in agent.According to the specific example of the present invention, organic solvent can be at least one in Isosorbide-5-Nitrae dioxane, DMF, acetonitrile
Kind.Thus in above-mentioned organic solvent system, compound shown in compound shown in formula 3 and formula 4 can be caused fully to react,
And then improve the yield of compound shown in formula 1.
According to a particular embodiment of the invention, the alkali contained in above-mentioned organic solvent can be thought as triethylamine.It is possible thereby to
Further promote compound shown in formula 3 to be reacted with compound shown in formula 4, and cause compound shown in formula 4 optionally
The fluorine on 6 on compound quinolone phenyl ring shown in substitution formula 3, and then compound shown in formula 1 can effectively be prepared.
According to the specific example of the present invention, triethylamine is the acid binding agent of step reaction, and main function is that will be produced in reaction
Hydrogen fluoride be changed into the hydrofluoride of triethylamine, to promote to react more preferable conversion.Therefore, by adding appropriate triethylamine
The reaction efficiency of the step can be further improved, improves the yield of the compound of formula 1.
According to a particular embodiment of the invention, compound shown in formula 3 and compound shown in formula 4 are under 80-100 degrees Celsius
What reaction 4-20 hours completed.It is possible thereby to so that compound shown in formula 3 is fully reacted with compound shown in formula 4, to enter one
Walk the yield of compound shown in raising formula 1.
According to the specific example of the present invention, inventor has found that reaction temperature is too low or the reaction time is too short, and substrate formula 3 is changed
The conversion ratio of compound is all relatively low, because the polarity of the compound of substrate formula 3, the compound of product formula 1 and accessory substance MOXIFLOXACIN is nearer, body
The incomplete conversion of system will cause the complexity of postprocessing working procedures.System is chosen is reacted at a relatively high temperature, mainly
To accelerate the step reaction rate, content of the compound of increase product formula 1 in system, it is easy to the follow-up compound of product formula 1
Separation and purifying.
According to a particular embodiment of the invention, the mass ratio of compound shown in formula 3 and compound shown in formula 4 is 0.7-1.3：
1.It is possible thereby to so that compound shown in formula 3 is fully reacted with compound shown in formula 4, while save cost of material.
According to a particular embodiment of the invention, the concentration of triethylamine in organic solvent is 0.1-0.3 volumes %.Thus plus
Entering the triethylamine of aforementioned proportion can further promote compound shown in formula 3 to be reacted with compound shown in formula 4 so that shown in formula 4
Compound optionally substitutes the fluorine on 6 on compound quinolone phenyl ring shown in formula 3, and then formula can effectively be prepared
Compound shown in 1.
Embodiment 1
Reaction：Compound, 100mL absolute methanols shown in 10g formula 2 are added in 250mL round-bottomed flasks, after stirring and evenly mixing
13.3mL 36% hydrochloric acid is slow added into, charging finishes；System is warming up to 65 DEG C, at this temperature stirring reaction 15h；
Post processing：After reaction terminates, system is cooled to 10 DEG C, stirring and crystallizing 2h, and system decompression filtration, filter cake uses 20mL
Absolute methanol washs, and after being dried in vacuo 8h at 60 DEG C, obtains compound shown in 8.86g formulas 3, yield：96.83%；
Embodiment 2
Reaction：Compound, 120mL absolute ethyl alcohols shown in 12g formula 2 are added in 250mL round-bottomed flasks, after stirring and evenly mixing
19mL 36% hydrochloric acid is slow added into, charging finishes；System is warming up to 75 DEG C, at this temperature stirring reaction 12h；
Post processing：After reaction terminates, system is cooled to 15 DEG C, stirring and crystallizing 3h, and system decompression filtration, filter cake uses 20mL
Absolute ethyl alcohol washs, and after being dried in vacuo 10h at 70 DEG C, obtains compound shown in 9.15g formulas 3, yield：83.79%；
Embodiment 3
Reaction：Compound, 150mL isopropanols shown in 8g formula 2 are added in 250mL round-bottomed flasks, after stirring and evenly mixing again
11.6mL 36% hydrochloric acid is slowly added to, charging finishes；System is warming up to 83 DEG C, at this temperature stirring reaction 8h；
Post processing：After reaction terminates, system is cooled to 10 DEG C, stirring and crystallizing 2h, and system decompression filtration, filter cake uses 20mL
Isopropanol washs, and after being dried in vacuo 12h at 80 DEG C, obtains compound shown in 6.77g formulas 3, yield：92.87%；
Embodiment 4
Reaction：Compound, 180mL drinking water shown in 15g formula 2 are added in 250mL round-bottomed flasks, after stirring and evenly mixing again
24mL 36% hydrochloric acid is slowly added to, charging finishes；System is warming up to 95 DEG C, at this temperature stirring reaction 12h；
Post processing：After reaction terminates, system is cooled to 15 DEG C, stirring and crystallizing 3h, and system decompression filtration, filter cake uses 40mL
Water washing is drunk, after being dried in vacuo 15h at 85 DEG C, obtains compound shown in 12.14g formulas 3, yield：88.61%；
Embodiment 5
Reaction：Compound, 100mL drinking water and the anhydrous second of 100mL shown in 12g formula 2 are added in 250mL round-bottomed flasks
Alcohol, is slow added into 19mL 36% hydrochloric acid after stirring and evenly mixing, charging finishes；System is warming up to 90 DEG C, and stirring is anti-at this temperature
Answer 20h；
Post processing：After reaction terminates, system is cooled to 10 DEG C, stirring and crystallizing 2h, and system decompression filtration, filter cake uses 20mL
Water washing is drunk, after being dried in vacuo 15h at 80 DEG C, obtains compound shown in 9.52g formulas 3, yield：87.18%；
Embodiment 6
Reaction：Compound, 50mL Isosorbide-5-Nitraes-dioxane shown in 5g formulas 3 are added in 100mL round-bottomed flask, stirring is mixed
It is even after disposably adding compound shown in 4.27g formula 4 in system, it is rear disposable to add 7mL triethylamines；Charging finishes, body
System is warming up to 85 DEG C, at this temperature stirring reaction 5h.
Post processing：After reaction terminates, system is cooled to 70 DEG C, and reaction solution is concentrated under reduced pressure into dry, obtains brownish black grease formula 1
Shown crude compound.
Purifies and separates：To compound shown in prepared crude product formula 1, column chromatography purifies and separates (eluant, eluent；Ethyl acetate:
Methanol=5:1), the component liquid of compound shown in formula 1 is concentrated under reduced pressure into dry, obtains compound shown in 1.12g brown solids formula 1,
Yield 16.47%.
Embodiment 7
Reaction：Compound, 60mL DMF shown in 8g formulas 3 are added in 100mL round-bottomed flask, is stirred and evenly mixed after system
In compound shown in the disposable formula 4 for adding 10.26g, it is rear disposable to add 15mL triethylamines；Charging is finished, and system is warming up to
95 DEG C, stirring reaction 4h at this temperature.
Post processing：After reaction terminates, system is cooled to 80 DEG C, and reaction solution is concentrated under reduced pressure into dry, obtains brownish black grease formula 1
Shown crude compound.
Purifies and separates：To compound shown in prepared crude product formula 1, column chromatography purifies and separates (eluant, eluent；Ethyl acetate:
Methanol=5:2), the component liquid of compound shown in formula 1 is concentrated under reduced pressure into dry, obtains compound shown in 0.96g brown solids formula 1,
Yield 8.82%.
Embodiment 8
Reaction：Compound, 80mL acetonitriles shown in 10g formulas 3 are added in 100mL round-bottomed flask, is stirred and evenly mixed after body
Compound shown in 8.55g formula 4, rear disposable addition 18.8mL triethylamines are disposably added in system；Charging finishes, system heating
To 80 DEG C, stirring reaction 20h at this temperature.
Post processing：After reaction terminates, system is cooled to 50 DEG C, and reaction solution is concentrated under reduced pressure into dry, obtains brownish black grease formula 1
Shown crude compound.
Purifies and separates：To compound shown in prepared crude product formula 1, column chromatography purifies and separates (eluant, eluent；Ethyl acetate),
The component liquid of compound shown in formula 1 is concentrated under reduced pressure into dry, obtains compound shown in 1.31g brown solids formula 1, yield 9.63%.
Embodiment 9
The Structural Identification of compound shown in formula 1
To compound shown in the formula 1 after above-mentioned purifies and separates, carry out corresponding HPLC-MS,1HNMR, its corresponding experiment
Data and interpretation of result are as shown in the table：
A：HPLC-MS is analyzed, and as a result sees Fig. 1.Wherein, quasi-molecular ions [M+1]：402.2.
B：1HNMR is analyzed, and as a result sees Fig. 2.
C：13C-NMR is analyzed, and as a result sees Fig. 3.
Molecular formula, C21H24FN3O
1HNMR (400MHz, DMSO), δ：8.59 (s, 1H), 7.16~7.18 (S, 1H), 4.18 (s, 2H), 4.00 (S,
4H), 3.09~3.11 (m, 3H), 2.82 (m, 2H), 2.58 (m, 1H), 1.61~1.78 (m, 3H), 1.36 (m, 1H), 1.15~
1.23 (m, 3H), 1.10~1.30 (m, 2H)；(referring to Fig. 2)
To sum up state, foundation HPLC-MS,1HNMR testing results understand that compound structure shown in prepared formula 1 is as follows：
Fig. 4 be the isolated compound of formula 1 HMBC (1H→13C) full figure, Fig. 5 and Fig. 6 be respectively HMBC (1H→13C)
The partial enlarged drawing of full figure.Fig. 7 is the HSQC figures of compound shown in formula 1.It is possible thereby to compound shown in formula 1 is further proved
Structural formula.
In the description of this specification, reference term " one embodiment ", " some embodiments ", " example ", " specifically show
The description of example " or " some examples " etc. means specific features, structure, material or the spy for combining the embodiment or example description
Point is contained at least one embodiment or example of the present invention.In this manual, to the schematic representation of above-mentioned term not
Identical embodiment or example must be directed to.Moreover, specific features, structure, material or the feature of description can be any
Combined in an appropriate manner in individual or multiple embodiments or example.In addition, in the case of not conflicting, the technology of this area
Different embodiments or example and the feature of different embodiments or example described in this specification can be combined by personnel
And combination.
Although embodiments of the invention have been shown and described above, it is to be understood that above-described embodiment is example
Property, it is impossible to limitation of the present invention is interpreted as, one of ordinary skill in the art within the scope of the invention can be to above-mentioned
Embodiment is changed, changed, replacing and modification.
Claims (11)
- A kind of 1. compound, it is characterised in that the compound has structure shown in formula 1,
- A kind of 2. method for preparing compound described in claim 1, it is characterised in that including：(1) reaction is hydrolyzed in compound shown in formula 2, to obtain compound shown in formula 3；(2) compound shown in compound shown in formula 3 and formula 4 is reacted, to obtain compound shown in formula 1,
- 3. according to the method for claim 2, it is characterised in that in step (1), compound shown in formula 2 is in hydrochloric acid and first The hydrolysis is carried out in alcoholic solution.
- 4. according to the method for claim 2, it is characterised in that in step (1), the hydrolysis is Celsius in 50-60 14-16 hour completions are carried out under conditions of degree.
- 5. according to the method for claim 3, it is characterised in that in step (1), the concentration of the hydrochloric acid is 36 volume %, The volume ratio of the hydrochloric acid and the methanol is 10-20：100.
- 6. according to the method for claim 5, it is characterised in that in step (1), compound shown in formula 2 and the hydrochloric acid Mass volume ratio is 1g：2-10ml.
- 7. according to the method for claim 2, it is characterised in that in step (2), chemical combination shown in compound shown in formula 3 and formula 4 Thing is carried out in the organic solvent containing alkali, and the organic solvent is at least one in Isosorbide-5-Nitrae dioxane, DMF, acetonitrile Kind.
- 8. according to the method for claim 7, it is characterised in that in step (2), it is triethylamine that the alkali, which is,.
- 9. according to the method for claim 8, it is characterised in that in step (2), compound shown in formula 3 and chemical combination shown in formula 4 Thing is to react 4-20 hours under 80-100 degrees Celsius to complete.
- 10. according to the method for claim 2, it is characterised in that in step (2), compound shown in formula 3 and shownization of formula 4 The mass ratio of compound is 0.7-1.3：1.
- 11. according to the method for claim 8, it is characterised in that in step (2), the triethylamine is in the organic solvent In concentration be 0.1-0.3 volumes %.
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| CN110878047A (en) * | 2019-12-09 | 2020-03-13 | 怀化学院 | Gatifloxacin carboxylic acid and its synthesis method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945399A (en) * | 2014-03-26 | 2015-09-30 | 南京优科生物医药研究有限公司 | Method for preparing Moxifloxacin impurity C |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104945399A (en) * | 2014-03-26 | 2015-09-30 | 南京优科生物医药研究有限公司 | Method for preparing Moxifloxacin impurity C |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110878047A (en) * | 2019-12-09 | 2020-03-13 | 怀化学院 | Gatifloxacin carboxylic acid and its synthesis method |
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Application publication date: 20180309 |