CS268491B1 - 7-chloro-1-(2,4 dinitrophynel)-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxyl acid - Google Patents
7-chloro-1-(2,4 dinitrophynel)-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxyl acid Download PDFInfo
- Publication number
- CS268491B1 CS268491B1 CS887759A CS775988A CS268491B1 CS 268491 B1 CS268491 B1 CS 268491B1 CS 887759 A CS887759 A CS 887759A CS 775988 A CS775988 A CS 775988A CS 268491 B1 CS268491 B1 CS 268491B1
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- CS
- Czechoslovakia
- Prior art keywords
- oxoquinoline
- dihydro
- fluoro
- chloro
- dinitrophynel
- Prior art date
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- 239000002253 acid Substances 0.000 title 1
- JJILZTFRIUWSKB-UHFFFAOYSA-N [N+](=O)([O-])C1=C(C=CC(=C1)[N+](=O)[O-])N1C=C(C(C2=CC(=C(C=C12)Cl)F)=O)C(=O)O Chemical compound [N+](=O)([O-])C1=C(C=CC(=C1)[N+](=O)[O-])N1C=C(C(C2=CC(=C(C=C12)Cl)F)=O)C(=O)O JJILZTFRIUWSKB-UHFFFAOYSA-N 0.000 claims abstract description 4
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- VYZAHLCBVHPDDF-UHFFFAOYSA-N Dinitrochlorobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 VYZAHLCBVHPDDF-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- -1 alkyl 7-chloro-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylates Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- VLOYRWBXBBOLJW-UHFFFAOYSA-N ethyl 7-chloro-6-fluoro-4-oxo-1h-quinoline-3-carboxylate Chemical compound ClC1=C(F)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 VLOYRWBXBBOLJW-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 241000588767 Proteus vulgaris Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 229940007042 proteus vulgaris Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Řešeni se týká 7-chlor-l- (2,4- dinitrofenyl)—6—fíuor-1,4-dihydro-4- -oxochinolin-3-karboxylové kyseliny N0_ COOH I. 268 491 nn (13) Bl (51) Int. Cl.4 C 07 D 215/56 CS 2 6 8 4 9 1 81 Tato nové, doaud nepopsané létka vykazuje význaený antibakteriélnl účinek.The solution concerns 7-chloro-1- (2,4- dinitrophenyl) -6-fluoro-1,4-dihydro-4 -oxoquinoline-3-carboxylic acid N0_ COOH I. 268 491 nn (13) Bl (51) Int. ARTICLE 4 OJ C 07 D 215/56 EN 2 6 8 4 9 1 81 This new, doaud unspecified fly well-known antibacterial effect.
Description
Vynález se týká 7-chlor-l- (2,4-dinitrofenyl)-6~fluor-l,4-dihydro-4oxochinolin-3-karboxylové kyseliny vzorce IThe invention relates to 7-chloro-1- (2,4-dinitrophenyl) -6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid of formula I
(I).(AND).
Je známá vysoká účinnost řady substituovaných 1-sry1-6-fluor-l,4-dihydro4-oxochinolin-3-karboxylových kyselin proti řadě bakterii (Chu, D. T..íW, a spol.: J. Med. Chám. 28, 1558, 1985). Způsob přípravy těchto látek Je však obtížný a výchozí suroviny Jsou obtížně dostupné.The high potency of a number of substituted 1-aryl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acids against a number of bacteria is known (Chu, DT.W., et al., J. Med. Cham. 28, 1558, 1985). However, the method of preparation of these substances is difficult and the starting materials are difficult to obtain.
7-Chlor-l- (2,4-dinltrofenyl)-6-fluor-1,4~dihydro-4-oxochinolln-3-karboxylová kyselina Je nová, dosud nepopsaná látka, která má významnou antibakteriálni aktivitu. ·7-Chloro-1- (2,4-dinitrophenyl) -6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid It is a new, as yet undescribed substance that has significant antibacterial activity. ·
Jako výchozí sloučeninu pro přípravu látky vzorce I lze podle vynálezu použít snadno dosdupné alkyl 7-chlor-6-fluor-1,4-dihydro-4-oxochinolin-3-karboxyláty, kde alkyl obsahuje 1 až 4 atony uhlíku. Výchoz! ester lze podle vynálezu arylovat 2,4-dinitrohalogenbenzenem, s výhodou 2,4-dinitrochlorbenzenem, v prostředí aprotického rozpouštědla, s výhodou dimethylformamidu, po předchozím převedení na alkalickou sůl pomocí alkalického hydridu, s výhodou hydrIdu sodného. Vzniklý alkyl 7-chlor-l- (2,4-dinitrofenyl)-6-fluor-l,4-dihydro-4-oxochinolin-3karboxylát lze přímo převést hydrolýzou v kyselém prostředí na sloučeninu vzorce I. 'Easily available alkyl 7-chloro-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylates, wherein the alkyl contains 1 to 4 carbon atoms, can be used as the starting compound for the preparation of the compound of formula I according to the invention. Default! According to the invention, the ester can be arylated with 2,4-dinitrohalobenzene, preferably 2,4-dinitrochlorobenzene, in an aprotic solvent, preferably dimethylformamide, after conversion to an alkali salt with an alkali hydride, preferably sodium hydride. The resulting alkyl 7-chloro-1- (2,4-dinitrophenyl) -6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate can be directly converted by hydrolysis in an acidic medium to a compound of formula I.
Sloučenina vzorce I byla testována in vitro na antibakteriální aktivitu.The compound of formula I was tested in vitro for antibacterial activity.
minimální inhibiční koncentrace Jsou uvedeny v ng/1:minimum inhibitory concentrations are given in ng / l:
Staphylococcus aureus2Staphylococcus aureus2
Streptococcus pyogenes64Streptococcus pyogenes64
Excherichla coll8Excherichla coll8
Proteus vulgaris$ 1Proteus vulgaris $ 1
Pseudomonas aeruginosa «s 1Pseudomonas aeruginosa «s 1
Způsob přípravy sloučeniny vzorce I podle vynálezu Je Jednoduchý, Bližší podrobnosti vyplývají z následujících příkladů provedení. Uvedené příklady vyná lez neomezuji.The process for the preparation of the compound of the formula I according to the invention is simple. More details are given in the following examples. I do not limit the above examples.
CS 268 491 BlCS 268 491 Bl
Příklad 1Example 1
K míchané směsi 2,7 g ethyl 7-chlor-6-fluor-l,4-dihydro-4-oxochinolin-3-karboxylátu (10 mmol) a 25 ml suchého dimethylformamidu bylo přidáno 0,5 g 55% disperze hydridu sodného v minerálním oleji a směs byla míchána za teploty aistnoati 1 h. Potom se přilil roztok 2,2 g 2,4-dinitrochlorbenzenu (11 mmol) v 10 ml euchého dime thylf ormamidu a směe byla míchána 12 h při teplotě 110 °C, Chladná aměa byla vlita do 200 ml vody, po ochlazení byl nerozpuetný podíl odsát, Krystallzací z dimethylformamidu bylo zlákáno 1,3 g ethyl 7-chlor-l. (2,4-dinitrofenyl)-6-fluor-l,4-dihydro-4-oxochinolin-3-karboxylátu o t. t, 263 až 268 °C (taje za rozkladu).To a stirred mixture of 2.7 g of ethyl 7-chloro-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate (10 mmol) and 25 mL of dry dimethylformamide was added 0.5 g of a 55% dispersion of sodium hydride in mineral oil and the mixture was stirred at room temperature for 1 h. A solution of 2.2 g of 2,4-dinitrochlorobenzene (11 mmol) in 10 ml of dry dimethylformamide was then added and the mixture was stirred at 110 ° C for 12 h. was poured into 200 ml of water, after cooling the insoluble matter was filtered off with suction. 1.3 g of ethyl 7-chloro-1 were leached by crystallization from dimethylformamide. (2,4-dinitrophenyl) -6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate, m.p. 263-268 ° C (melts with decomposition).
Směs 0,44 g takto získaného esteru (1 mmol), 4 ml octové kyseliny a 4 ml koncentrované chlorovodíkové kyseliny (37 %) byla vařena pod zpětným chladičem 8 h. Po ochlazení byl nerozpustný podíl odsát a promyt vodou. Kryatalizaci z dimethylformamidu bylo získáno 0,23 g látky o t. t. 290 až 298 °C (taje za rozkladu).A mixture of 0.44 g of the ester thus obtained (1 mmol), 4 ml of acetic acid and 4 ml of concentrated hydrochloric acid (37%) was refluxed for 8 h. After cooling, the insoluble matter was filtered off with suction and washed with water. Crystallization from dimethylformamide gave 0.23 g of m.p. 290-298 ° C (melting with decomposition).
Příklad 2Example 2
K míchané směsi 2,7 g ethyl 7-chlor-6-fluor-l,4-dihydro-4-oxochinolin-3-ksrboxylátu (10 mmol) a 25 ml suxhého dimethylformamidu bylo přidáno 0,5 g 55 % disperze hydridu sodného v minerálním oleji e směs byla míchána za teploty aíetnoeti 2 h. Potom se přilil roztok 2,2 g 2,4-dinitrochlorbenzenu (11 mmol) v 10 ml euchého dimethylf ormamidu a směs byla míchána 15 h při teplotě 110 °C, Chladná reakční směs byla odpařena k suchu, odparek byl převeden pomocí 50 ml octové kyeeliny do baňky opatřené míchadlem a zpětným chladičem a po přidáni 50 ml koncentrované chlorovodíkové kyseliny byla eměs vařena 8 h pod zpětným chladičem. Po ochlazení byl nerozpuetný podíl odsát, promyt vodou a-vysuěen, Suchý surový produkt byl krystalizován z dimethylf ormamidu. Bylo získáno 2,1 g látky (51 %) o t. t. 290 až 298 °C (taje za rozkladu).To a stirred mixture of 2.7 g of ethyl 7-chloro-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate (10 mmol) and 25 ml of sily dimethylformamide was added 0.5 g of a 55% dispersion of sodium hydride in A solution of 2.2 g of 2,4-dinitrochlorobenzene (11 mmol) in 10 ml of dry dimethylformamide was added and the mixture was stirred at 110 DEG C. for 15 h. It was evaporated to dryness, the residue was transferred with 50 ml of acetic acid to a flask equipped with a stirrer and a reflux condenser, and after adding 50 ml of concentrated hydrochloric acid, the mixture was refluxed for 8 hours. After cooling, the insoluble matter was filtered off with suction, washed with water and dried. The dry crude product was crystallized from dimethylformamide. 2.1 g of material (51%) with a melting point of 290-298 ° C (melting with decomposition) were obtained.
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Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS887759A CS268491B1 (en) | 1988-11-25 | 1988-11-25 | 7-chloro-1-(2,4 dinitrophynel)-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxyl acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS887759A CS268491B1 (en) | 1988-11-25 | 1988-11-25 | 7-chloro-1-(2,4 dinitrophynel)-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxyl acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS775988A1 CS775988A1 (en) | 1989-08-14 |
| CS268491B1 true CS268491B1 (en) | 1990-03-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS887759A CS268491B1 (en) | 1988-11-25 | 1988-11-25 | 7-chloro-1-(2,4 dinitrophynel)-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxyl acid |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS268491B1 (en) |
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1988
- 1988-11-25 CS CS887759A patent/CS268491B1/en unknown
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| Publication number | Publication date |
|---|---|
| CS775988A1 (en) | 1989-08-14 |
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