CA1340561C - Methode de preparation de ciprofloxacine - Google Patents

Methode de preparation de ciprofloxacine

Info

Publication number: CA1340561C
Authority: CA; Canada
Prior art keywords: formula; compound; organic solvent; acetic anhydride; sodium
Prior art date: 1988-06-13
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA000602049A

Other languages

English (en)

Inventor

Isidro Lopez Molina

Alberto Palomo Coll

Antonio Domingo Coto

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Union Quimico Farmaceutica SA

Original Assignee

Union Quimico Farmaceutica SA

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1988-06-13

Filing date

1989-06-07

Publication date

1999-05-25

1989-06-07 Application filed by Union Quimico Farmaceutica SA filed Critical Union Quimico Farmaceutica SA

1999-05-25 Application granted granted Critical

1999-05-25 Publication of CA1340561C publication Critical patent/CA1340561C/fr

2016-05-25 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 title claims abstract description 13
229960003405 ciprofloxacin Drugs 0.000 title abstract description 9
238000004519 manufacturing process Methods 0.000 title abstract description 8
150000001875 compounds Chemical class 0.000 claims abstract description 40
238000006243 chemical reaction Methods 0.000 claims abstract description 14
239000002253 acid Substances 0.000 claims abstract description 9
150000002084 enol ethers Chemical class 0.000 claims abstract description 8
HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 claims abstract description 7
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims abstract description 6
LNOQURRKNJKKBU-UHFFFAOYSA-N ethyl piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCNCC1 LNOQURRKNJKKBU-UHFFFAOYSA-N 0.000 claims abstract description 4
230000003647 oxidation Effects 0.000 claims abstract description 4
238000007254 oxidation reaction Methods 0.000 claims abstract description 4
238000007363 ring formation reaction Methods 0.000 claims abstract description 4
238000005904 alkaline hydrolysis reaction Methods 0.000 claims abstract description 3
238000006386 neutralization reaction Methods 0.000 claims abstract description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 51
238000000034 method Methods 0.000 claims description 32
230000008569 process Effects 0.000 claims description 25
239000000203 mixture Substances 0.000 claims description 23
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
238000002360 preparation method Methods 0.000 claims description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
239000003960 organic solvent Substances 0.000 claims description 13
KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 claims description 8
238000010992 reflux Methods 0.000 claims description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
239000005708 Sodium hypochlorite Substances 0.000 claims description 5
238000010438 heat treatment Methods 0.000 claims description 5
239000012312 sodium hydride Substances 0.000 claims description 5
229910000104 sodium hydride Inorganic materials 0.000 claims description 5
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 5
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical group [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
230000009471 action Effects 0.000 claims description 4
238000004821 distillation Methods 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
150000003839 salts Chemical class 0.000 claims description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 2
239000006227 byproduct Substances 0.000 claims description 2
229960001760 dimethyl sulfoxide Drugs 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
150000004677 hydrates Chemical class 0.000 claims description 2
230000007062 hydrolysis Effects 0.000 claims description 2
238000006460 hydrolysis reaction Methods 0.000 claims description 2
229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims 4
239000003513 alkali Substances 0.000 claims 3
239000002585 base Substances 0.000 claims 3
229910015900 BF3 Inorganic materials 0.000 claims 2
229910001854 alkali hydroxide Inorganic materials 0.000 claims 2
150000008044 alkali metal hydroxides Chemical class 0.000 claims 2
239000012736 aqueous medium Substances 0.000 claims 2
ZPFNNJJRURYIGW-UHFFFAOYSA-N 1-(3,6-dichloro-3-fluorocyclohexa-1,5-dien-1-yl)butane-1,3-dione Chemical compound ClC=1C(=CC(CC1)(F)Cl)C(CC(C)=O)=O ZPFNNJJRURYIGW-UHFFFAOYSA-N 0.000 claims 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims 1
239000002609 medium Substances 0.000 claims 1
230000001590 oxidative effect Effects 0.000 claims 1
CRWJEUDFKNYSBX-UHFFFAOYSA-N sodium;hypobromite Chemical compound [Na+].Br[O-] CRWJEUDFKNYSBX-UHFFFAOYSA-N 0.000 claims 1
WHZMLJFJMRIQBA-UHFFFAOYSA-N 1-(2,4-dichloro-5-fluorophenyl)butane-1,3-dione Chemical compound CC(=O)CC(=O)C1=CC(F)=C(Cl)C=C1Cl WHZMLJFJMRIQBA-UHFFFAOYSA-N 0.000 abstract description 5
241000894006 Bacteria Species 0.000 abstract description 2
239000003899 bactericide agent Substances 0.000 abstract description 2
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 abstract 1
239000000243 solution Substances 0.000 description 15
239000007787 solid Substances 0.000 description 10
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
239000007858 starting material Substances 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
BDJZCCWUSOZUQG-UHFFFAOYSA-N 2,4-dichloro-1-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1Cl BDJZCCWUSOZUQG-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
238000001914 filtration Methods 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
230000010933 acylation Effects 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000002002 slurry Substances 0.000 description 3
FAKJFAMIABOKBW-UHFFFAOYSA-N 1-(2,4-dichloro-5-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC(F)=C(Cl)C=C1Cl FAKJFAMIABOKBW-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
OKZIUSOJQLYFSE-UHFFFAOYSA-N difluoroboron Chemical compound F[B]F OKZIUSOJQLYFSE-UHFFFAOYSA-N 0.000 description 2
JGJLWPGRMCADHB-UHFFFAOYSA-N hypobromite Chemical compound Br[O-] JGJLWPGRMCADHB-UHFFFAOYSA-N 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
239000000463 material Substances 0.000 description 2
230000008018 melting Effects 0.000 description 2
238000002844 melting Methods 0.000 description 2
125000000896 monocarboxylic acid group Chemical group 0.000 description 2
239000003921 oil Substances 0.000 description 2
238000000819 phase cycle Methods 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000000376 reactant Substances 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
230000011514 reflex Effects 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
XOCIDZJVMALWLH-UHFFFAOYSA-N 1-(2,4-dichloro-5-fluorophenyl)-2-(ethoxymethylidene)butane-1,3-dione Chemical compound ClC1=C(C(=O)C(C(C)=O)=COCC)C=C(C(=C1)Cl)F XOCIDZJVMALWLH-UHFFFAOYSA-N 0.000 description 1
YLHUPYSUKYAIBW-UHFFFAOYSA-N 1-acetylpyrrolidin-2-one Chemical compound CC(=O)N1CCCC1=O YLHUPYSUKYAIBW-UHFFFAOYSA-N 0.000 description 1
CVBUKMMMRLOKQR-UHFFFAOYSA-N 1-phenylbutane-1,3-dione Chemical compound CC(=O)CC(=O)C1=CC=CC=C1 CVBUKMMMRLOKQR-UHFFFAOYSA-N 0.000 description 1
LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
KZCWJHUTTSVCRO-UHFFFAOYSA-N 2,4-dichloro-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(Cl)C=C1Cl KZCWJHUTTSVCRO-UHFFFAOYSA-N 0.000 description 1
IGSFOXNHUBLZHU-UHFFFAOYSA-N 2,4-dichloro-5-methylaniline Chemical compound CC1=CC(N)=C(Cl)C=C1Cl IGSFOXNHUBLZHU-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
NCACZPKRIFFGHB-UHFFFAOYSA-N 3-acetyl-3h-quinolin-4-one Chemical compound C1=CC=C2C(=O)C(C(=O)C)C=NC2=C1 NCACZPKRIFFGHB-UHFFFAOYSA-N 0.000 description 1
RVDLHGSZWAELAU-UHFFFAOYSA-N 5-tert-butylthiophene-2-carbonyl chloride Chemical compound CC(C)(C)C1=CC=C(C(Cl)=O)S1 RVDLHGSZWAELAU-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
238000003512 Claisen condensation reaction Methods 0.000 description 1
238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
LVZGQWKTUCVPBQ-UHFFFAOYSA-N acetic acid;trifluoroborane Chemical compound CC(O)=O.FB(F)F LVZGQWKTUCVPBQ-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
229940040526 anhydrous sodium acetate Drugs 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000007810 chemical reaction solvent Substances 0.000 description 1
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003480 eluent Substances 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
UNWSCLFRWCYCHG-UHFFFAOYSA-N ethyl acetate;trifluoroborane Chemical compound FB(F)F.CCOC(C)=O UNWSCLFRWCYCHG-UHFFFAOYSA-N 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
238000010525 oxidative degradation reaction Methods 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000000047 product Substances 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
229910000342 sodium bisulfate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 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
- C07D401/02—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 two hetero rings
- C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Steroid Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA000602049A 1988-06-13 1989-06-07 Methode de preparation de ciprofloxacine Expired - Fee Related CA1340561C (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
ES8801824A ES2006977A6 (es)	1988-06-13	1988-06-13	Procedimiento para la obtencion de ciprofloxacina.
ES8801824		1988-06-13

Publications (1)

Publication Number	Publication Date
CA1340561C true CA1340561C (fr)	1999-05-25

Family

ID=8256776

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000602049A Expired - Fee Related CA1340561C (fr)	1988-06-13	1989-06-07	Methode de preparation de ciprofloxacine

Country Status (5)

Country	Link
KR (1)	KR920001134B1 (fr)
CA (1)	CA1340561C (fr)
ES (1)	ES2006977A6 (fr)
GR (1)	GR1000405B (fr)
PT (1)	PT90832B (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5650533A (en) *	1989-09-11	1997-07-22	Rhone-Poulenc Agriculture Ltd.	Intermediates to herbicidal 4-substituted isoxazoles
ES2036941B1 (es) *	1991-11-07	1994-01-16	Inke Sa	Procedimiento para la obtencion del acido 1-(2,4-difluorofenil)-6-fluoro-7-(3-metil-1-piperacinil)-4-oxo-1,4-dihidroquinolin-3-carboxilico y sus sales.
KR100437600B1 (ko) *	1999-08-17	2004-06-26	엘지전자 주식회사	부가통신 시스템에서의 문자 정보 변환 서비스 보드 및 방법

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3248505A1 (de) *	1982-12-29	1984-07-05	Bayer Ag, 5090 Leverkusen	1-cyclopropyl-6-fluor-1,4-dihydro-4-oxo-7(4- (oxoalkyl)-1-piperazinyl/-3-chinolincarbonsaeuren und ihre derivate, verfahren zu ihrer herstellung sowie diese enthaltende antibakterielle mittel

1988
- 1988-06-13 ES ES8801824A patent/ES2006977A6/es not_active Expired
1989
- 1989-05-25 GR GR890100344A patent/GR1000405B/el not_active IP Right Cessation
- 1989-06-07 CA CA000602049A patent/CA1340561C/fr not_active Expired - Fee Related
- 1989-06-12 PT PT90832A patent/PT90832B/pt not_active IP Right Cessation
- 1989-06-13 KR KR1019890008089A patent/KR920001134B1/ko not_active Expired

Also Published As

Publication number	Publication date
PT90832B (pt)	1994-12-30
GR890100344A (en)	1990-05-11
ES2006977A6 (es)	1989-05-16
KR920001134B1 (ko)	1992-02-06
PT90832A (pt)	1989-12-29
KR910000701A (ko)	1991-01-30
GR1000405B (el)	1992-06-30

Legal Events

Date	Code	Title	Description
2004-05-25	MKLA	Lapsed

Publication	Publication Date	Title
CA2176788C (fr)	2007-01-09	Methode de preparation d'acide 4-trifluoromethylnicotinique
US5728841A (en)	1998-03-17	Process for preparing 1-amino-1,2,3-triazole
CA1340561C (fr)	1999-05-25	Methode de preparation de ciprofloxacine
FI84072B (fi)	1991-06-28	Mellanprodukt foer framstaellning av norfloxacin och foerfarande foer dess framstaellning.
CA2199645C (fr)	1999-06-29	Methodes de fabrication de derives et d'intermediaires de l'acide quinolone-carboxylique
EP0230946A2 (fr)	1987-08-05	Procédé pour la préparation des dérivés de l'acide quinolonecarboxylique
EP0271275B1 (fr)	1991-11-27	Acide trifluorhydroxyaromatique et sa fabrication
HU198200B (en)	1989-08-28	Process for production of derivatives of quinoline carbonic acid
US4182880A (en)	1980-01-08	1,8-Naphthyridine compounds and process for preparing the same
EP0725785B1 (fr)	1997-07-23	Procede de preparation de rufloxacine et sels de celle-ci
EP0349217A2 (fr)	1990-01-03	Procédé de préparation de bronopol
KR100589966B1 (ko)	2006-06-15	베타-케토에스테르 화합물의 제조방법
KR940007307B1 (ko)	1994-08-12	1-사이클로프로필-7-클로로-6-플루오로-1,4-디하이드로-4-옥소퀴놀린-3-카복실산의 제조방법
EP0309626B1 (fr)	1992-05-06	Procédé de préparation de dérivés de dibenzothiépine
JPS62228038A (ja)	1987-10-06	芳香族ケトンの製法
CA2276320C (fr)	2007-10-30	Compose de l-tartre de trans-(-)-4-(4-fluorophenyle)-3-hydroxymethylpiperidine et processus de preparation de celui-ci
JPH0952893A (ja)	1997-02-25	キノロンカルボン酸誘導体の工業的な製造法およびその合成中間体
HU196415B (en)	1988-11-28	Process for preparing quinoline carboxylic acid boric acid anhydrides
KR930000439B1 (ko)	1993-01-21	퀴놀론 유도체의 제조방법
US5703233A (en)	1997-12-30	Quinilone disulfide as intermediates
HU195758B (en)	1988-07-28	Process for production of 2,3,4,5-tetrafluor-benzoilacetates
RU2049783C1 (ru)	1995-12-10	Способ получения производных хинолинкарбоновых кислот или их фармацевтически приемлемых солей
JPS63264440A (ja)	1988-11-01	２，４，５−トリフルオロ−３−ヒドロキシ安息香酸及びその製造法
KR950008528B1 (ko)	1995-07-31	할로겐화 퀴놀린 카복실산의 제조방법
JPH11302216A (ja)	1999-11-02	ジアルコキシ置換インダノン誘導体の製造方法