CN104876911A - Simple method for synthesizing delafloxacin - Google Patents
Simple method for synthesizing delafloxacin Download PDFInfo
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- CN104876911A CN104876911A CN201410068991.7A CN201410068991A CN104876911A CN 104876911 A CN104876911 A CN 104876911A CN 201410068991 A CN201410068991 A CN 201410068991A CN 104876911 A CN104876911 A CN 104876911A
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- lasha star
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- 238000000034 method Methods 0.000 title claims abstract description 17
- DYDCPNMLZGFQTM-UHFFFAOYSA-N delafloxacin Chemical compound C1=C(F)C(N)=NC(N2C3=C(Cl)C(N4CC(O)C4)=C(F)C=C3C(=O)C(C(O)=O)=C2)=C1F DYDCPNMLZGFQTM-UHFFFAOYSA-N 0.000 title abstract 3
- 229950006412 delafloxacin Drugs 0.000 title abstract 3
- 230000002194 synthesizing effect Effects 0.000 title abstract 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 16
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 16
- 239000002994 raw material Substances 0.000 claims abstract description 11
- 230000007062 hydrolysis Effects 0.000 claims abstract description 9
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 9
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 6
- 238000009833 condensation Methods 0.000 claims abstract 2
- 230000005494 condensation Effects 0.000 claims abstract 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 10
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 7
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 5
- ADVOBTAWDYIPGR-UHFFFAOYSA-N ethyl 3-oxohexanoate 3-(trifluoromethyl)benzonitrile Chemical class C(C)OC(CC(=O)CCC)=O.FC(C=1C=CC=C(C#N)C1)(F)F ADVOBTAWDYIPGR-UHFFFAOYSA-N 0.000 claims description 5
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 5
- -1 3-chloro-2,4,5-trifluoromethyl benzonitrile ethyl acetoacetic acid ethyl ester Chemical compound 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000002798 polar solvent Substances 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 239000000376 reactant Substances 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 3
- 235000015320 potassium carbonate Nutrition 0.000 claims description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003233 pyrroles Chemical class 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- CPWNLBDWIDFSBT-UHFFFAOYSA-N 5-(3-chloro-2,4,5-trifluorophenyl)-5-oxopentanoic acid Chemical compound C1=C(C(=C(C(=C1F)F)Cl)F)C(=O)CCCC(=O)O CPWNLBDWIDFSBT-UHFFFAOYSA-N 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 5
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
- 0 *C(CC(c(cc(c(F)c1Cl)F)c1F)=O)=O Chemical compound *C(CC(c(cc(c(F)c1Cl)F)c1F)=O)=O 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- AKAMNXFLKYKFOJ-UHFFFAOYSA-N 2,4,5-trifluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C=C1F AKAMNXFLKYKFOJ-UHFFFAOYSA-N 0.000 description 1
- GCIUCMRUMOAHKR-UHFFFAOYSA-N 3,5-difluoropyridine-2,6-diamine Chemical compound NC1=NC(N)=C(F)C=C1F GCIUCMRUMOAHKR-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- VLRGXXKFHVJQOL-UHFFFAOYSA-N 3-chloropentane-2,4-dione Chemical compound CC(=O)C(Cl)C(C)=O VLRGXXKFHVJQOL-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- YUPLNQPVHQVNEX-UHFFFAOYSA-N NC(C(F)=C1)NC(N)=C1F Chemical compound NC(C(F)=C1)NC(N)=C1F YUPLNQPVHQVNEX-UHFFFAOYSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- UQUPQEUNHVVNKW-UHFFFAOYSA-N azetidin-1-ium-3-ol;chloride Chemical compound Cl.OC1CNC1 UQUPQEUNHVVNKW-UHFFFAOYSA-N 0.000 description 1
- GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940124307 fluoroquinolone Drugs 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention provides a simple method for synthesizing delafloxacin, and belongs to the medicament synthesis field. The method provided by the invention is a preparation method taking 3-chloro-2, 4, 5-trifluorobenzoylethylacetate as raw material, and finishing the reaction after five steps of condensation, substitution, cyclization, re-substritution and hydrolysis in one pot, so that the route for synthesis of the delafloxacin is shortened, the reaction condition is simple, post-treatment is simple, industrialization production is facilitated, and the yield and purity are improved.
Description
Technical field:
The present invention relates to a kind of easy method synthesis De Lasha star, belong to technical field of medicine synthesis.
Background technology:
De Lasha star is a kind of new fluoroquinolone compound, its action target spot is DNA of bacteria topoisomerase, this product has outstanding broad spectrum antibiotic activity and fungicidal activity, and its antimicrobial spectrum comprises the staphylococcus of responsive to quinolones to resistance and suis and to the faecalis of vancomycin sensitive and resistance and anerobe etc.Clinically show that it can be applicable to treatment community acquired pneumonia and skin soft-tissue infection, and treatment respiratory tract and urinary system infection.
At present, the synthesis for De Lasha star mainly contains following two kinds:
1, Chinese patent CN1201459A starts to synthesize De Lasha star from chloro-2,4, the 5-trifluoromethyl benzonitrile ethyl acetoacetic acid ethyl esters of 3-.What adopt in this reaction is the high temperature cyclization of DMF and salt of wormwood, and easily produce impurity, also need after cyclization to be hydrolyzed, reactions steps increases, and productive rate is lower.Reaction scheme is as follows:
2, being published in organic chemistry magazine (Org Process Res & Dev2006,4,751) and providing the new synthetic method of De Lasha star, is starting raw material from 2,4,5-trifluoro-benzoic acid, synthesis De Lasha star.Because need to carry out Selective chlorination at 8 in this reaction, so 7 hydroxyls need protection, reactions steps increases.And when 8 are carried out chloro, the substituting group of 7 easily ruptures, and severe reaction conditions, reaction yield is low, is not suitable for scale operation.Reaction scheme is as follows:
Summary of the invention:
The object of the invention is to chloro-2,4, the 5-trifluoromethyl benzonitrile ethyl acetoacetic acid ethyl esters of 3-for raw material, by single stage method, easily, prepare De Lasha star efficiently.
The present invention realizes by the following method, with 3-chloro-2,4,5-trifluoromethyl benzonitrile ethyl acetoacetic acid ethyl ester is raw material, with triethyl orthoformate and aceticanhydride reflux, reacted rear steaming except aceticanhydride and triethyl orthoformate, then added N-Methyl pyrrolidone and dissolve, then alkali exists 3 in situation, 5-bis-fluoro-2,6-diamino-pyridine is added drop-wise in above-mentioned solution, after HPLC monitoring reaction completes, adds catalyzer cyclization, after to be done, directly again added by 3-hydroxy azetidine, last direct hydrolysis obtains product, its synthetic route:
The present invention adopts one pot to change reaction, and simple to operate, condition is controlled, can obtain the De Lasha star of higher degree, shorten reaction time simultaneously, decrease operation steps and loss of product, improve the yield of De Lasha star.
One kettle way of the present invention produces De Lasha star, and its hydrolysis is hydrolyzed in polar solvent in the basic conditions, and temperature of reaction is 0 DEG C ~ 100 DEG C, and the reaction times is 2h ~ 10h.Preferentially choose 70 DEG C, reaction 4h.
One of the present invention easy method synthesis De Lasha star, its raw material 3-chloro-2,4, the mol ratio of 5-trifluoromethyl benzonitrile ethyl acetoacetic acid ethyl ester and reactant is 1: (1.0 ~ 2.0), the ratio of its Raw and reactant preferably 1: (1.1 ~ 1.2), because the very few reaction of raw material is incomplete, raw material too much affects the next step, and the purity of product is not enough.
Temperature of reaction is 0 DEG C ~ 100 DEG C, and the reaction times is 2h ~ 10h, and wherein preferable temperature is 35 DEG C ~ 55 DEG C, and the reaction times is 8 ~ 10h
Solvent required for reaction is N, dinethylformamide, N, N-dimethylacetamide amine amide, N-Methyl pyrrolidone, methyl-sulphoxide, 1, the mixed solvent of one or more in 4-dioxane, wherein preferred DMF and N-Methyl pyrrolidone, the solubleness of raw material and reactant is better compared with other, shorten the reaction times, improve reaction conversion ratio.
Answer required alkali to be the mixed base of one or more in salt of wormwood, sodium carbonate, sodium hydroxide, potassium hydroxide, diethylamine, triethylamine, 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene (DBU), pyridine, pyrroles.Wherein preferred DBU, the by product that reaction produces is less.
The catalyzer used in reaction is magnesium chloride, the mixing of one or more in lithium chloride, magnesium chloride, iron trichloride, cuprous chloride.Wherein preferred magnesium chloride and lithium chloride.Its consumption is less, does not need removing, directly can carry out the next step.
Being hydrolyzed required alkali in reaction is potassium hydroxide, sodium hydroxide, lithium hydroxide, wherein preferred potassium hydroxide.Required polar solvent is methyl alcohol, ethanol, n-propyl alcohol, Virahol, isopropylcarbinol.Wherein preferred alcohol and Virahol.
The present invention has following advantage in sum:
1 raw material used in the present invention is easy to get, and goes for scale operation.
2 the present invention use single stage method to produce, and synthetic route shortens, and reaction conditions is simple, and by product is less, and aftertreatment is easy, can obtain the product of higher degree.
Embodiment:
The following stated embodiment only have expressed embodiments of the present invention, and it describes comparatively concrete and detailed, but therefore can not be interpreted as the restriction to the scope of the claims of the present invention.It should be pointed out that for the person of ordinary skill of the art, under the prerequisite not departing from inventional idea of the present invention, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.
Below by embodiment, the present invention is further detailed explanation.
The synthesis of the fluoro-1-of the chloro-6-of embodiment: 8-(amino-3, the 5-difluoro pyridine-2-bases of 6-)-7-(3-hydroxyl-1-azelidinyl)-Isosorbide-5-Nitrae-dihydro-4-oxygen-3-quinoline carboxylic acid (De Lasha star)
3-chloro-2 is added in 50ml flask, 4, 5-trifluoromethyl benzonitrile ethyl acetoacetic acid ethyl ester (7g, 0.025mol), triethyl orthoformate (5.9g, 0.04mol) and aceticanhydride, reflux 3h ~ 5h, decompression steams unnecessary triethyl orthoformate and aceticanhydride, add the dilution of N-methyl-2-pyrrolidone, again by 2, 6-diamino-3, 5-difluoro pyridine suspendible (3.8g, 0.026mol) with N-Methyl pyrrolidone suspendible, be added drop-wise in above-mentioned solution, Lithium chloride (anhydrous) (2.6g) and DBU (4.6g is added after question response completes, 0.03mol) (1, 8-diazabicylo [5.4.0] 11 carbon-7-alkene), heated and stirred, HPLC monitoring reacts completely.And then 3-hydroxy azetidine hydrochloric acid (3.52g) is joined in above-mentioned solution, then drip DBU, continue reaction to complete.Adding the aqueous solution of Virahol and potassium hydroxide, heating hydrolysis, being hydrolyzed rear tune PH=3 has solid to separate out.Filter, washing, obtains yellow solid (7.82g), productive rate 71%.
MP：238-241℃
1HNMR(CDCl
3)14.32(brs，1H)，8.51(d，J＝0.7Hz，1H)，7.96(dd，J＝9.9，0.7Hz，1H)，7.64(d，J＝13.6Hz，1H)，6.92(s，2H)，5.86(d，J＝5.8Hz，1H)，4.89(m，12H)，4.32(m，1H)，4.18(m，2H)。
Claims (10)
1. an easy method synthesis De Lasha star, is characterized in that 3-chloro-2,4,5-trifluoromethyl benzonitrile ethyl acetoacetic acid ethyl ester is raw material, in same reactor, in organic solvent, under there is situation in catalyzer, first condensation, more amino replacement, rear direct cyclization, after cyclization completes, replace, last direct hydrolysis obtains product again, its synthetic route:
2. according to the easy method of the one described in claim 1 synthesis De Lasha star, it is characterized in that, described hydrolysis is hydrolyzed in polar solvent in the basic conditions, and temperature of reaction is 0 DEG C ~ 100 DEG C, and the reaction times is 2h ~ 10h.
3., according to the easy method synthesis of the one described in claim 1 De Lasha star, it is characterized in that, the mol ratio of chloro-2,4, the 5-trifluoromethyl benzonitrile ethyl acetoacetic acid ethyl esters of described raw material 3-and reactant is 1: (1.0 ~ 2.0).
4., according to the easy method synthesis of the one described in claim 1 De Lasha star, it is characterized in that, described temperature of reaction is 0 DEG C ~ 100 DEG C, and the reaction times is 2h ~ 10h.
5. according to the easy method synthesis of the one described in claim 1 De Lasha star, it is characterized in that, described solvent is DMF, N, the mixed solvent of one or more in N-dimethylacetamide amine amide, N-Methyl pyrrolidone, methyl-sulphoxide, Isosorbide-5-Nitrae-dioxane.
6. according to the easy method synthesis of the one described in claim 1 De Lasha star, it is characterized in that, described alkali is the mixed base of one or more in salt of wormwood, sodium carbonate, sodium hydroxide, potassium hydroxide, diethylamine, triethylamine, 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene (DBU), pyridine, pyrroles.
7., according to the easy method synthesis of the one described in claim 1 De Lasha star, it is characterized in that, described catalyzer is the mixing of one or more in magnesium chloride, lithium chloride, magnesium chloride, iron trichloride, cuprous chloride.
8. according to the hydrolysis described in claim 2, it is characterized in that, described temperature of reaction is 0 DEG C ~ 100 DEG C, and the reaction times is 2h ~ 10h.
9. according to the hydrolysis described in claim 2, it is characterized in that, described alkali is potassium hydroxide, sodium hydroxide, lithium hydroxide.
10. according to the hydrolysis described in claim 2, it is characterized in that, described polar solvent is methyl alcohol, ethanol, n-propyl alcohol, Virahol, isopropylcarbinol.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106619636A (en) * | 2015-10-28 | 2017-05-10 | 重庆医药工业研究院有限责任公司 | Delafloxacin impurity compounds and preparation methods thereof |
| CN108084161A (en) * | 2017-12-28 | 2018-05-29 | 北京沃邦医药科技有限公司 | The preparation method of De Lasha stars and its intermediate |
| CN108892639A (en) * | 2018-08-13 | 2018-11-27 | 云南民族大学 | A kind of method that high-efficiency environment friendly prepares carbostyril compound |
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| JP2005097116A (en) * | 1999-11-11 | 2005-04-14 | Wakunaga Pharmaceut Co Ltd | Alkali metal salt of quinolinecarboxylic acid derivative and method of purifying quinolinecarboxylic acid derivative using the same |
| WO2006015194A2 (en) * | 2004-07-30 | 2006-02-09 | Abbott Laboratories | Preparation of pyridonecarboxylic acid antibacterials |
-
2014
- 2014-02-27 CN CN201410068991.7A patent/CN104876911A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1201459A (en) * | 1995-09-22 | 1998-12-09 | 涌永制药株式会社 | Novel pyridonecarboxylic acid derivatives or their salts and antibacterial agent comprising same as active ingredient |
| JP2005097116A (en) * | 1999-11-11 | 2005-04-14 | Wakunaga Pharmaceut Co Ltd | Alkali metal salt of quinolinecarboxylic acid derivative and method of purifying quinolinecarboxylic acid derivative using the same |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106619636A (en) * | 2015-10-28 | 2017-05-10 | 重庆医药工业研究院有限责任公司 | Delafloxacin impurity compounds and preparation methods thereof |
| CN106619636B (en) * | 2015-10-28 | 2020-01-31 | 重庆医药工业研究院有限责任公司 | Impurity compound of delafloxacin and preparation method thereof |
| CN108084161A (en) * | 2017-12-28 | 2018-05-29 | 北京沃邦医药科技有限公司 | The preparation method of De Lasha stars and its intermediate |
| CN108892639A (en) * | 2018-08-13 | 2018-11-27 | 云南民族大学 | A kind of method that high-efficiency environment friendly prepares carbostyril compound |
| CN108892639B (en) * | 2018-08-13 | 2021-05-14 | 云南民族大学 | Efficient and environment-friendly method for preparing quinolone compounds |
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