FI113263B - Menetelmä 6-fluori-2-halogeenikinoliinin valmistamiseksi - Google Patents
Menetelmä 6-fluori-2-halogeenikinoliinin valmistamiseksi Download PDFInfo
- Publication number
- FI113263B FI113263B FI954750A FI954750A FI113263B FI 113263 B FI113263 B FI 113263B FI 954750 A FI954750 A FI 954750A FI 954750 A FI954750 A FI 954750A FI 113263 B FI113263 B FI 113263B
- Authority
- FI
- Finland
- Prior art keywords
- radical
- alkyl
- hal
- general formula
- difluoro
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 18
- 239000002253 acid Substances 0.000 claims abstract description 8
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 230000002140 halogenating effect Effects 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 69
- -1 phenyl-10 Chemical group 0.000 claims description 41
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- BJVCSICIEDHBNI-UHFFFAOYSA-N benzo[b][1,8]naphthyridine Chemical class N1=CC=CC2=CC3=CC=CC=C3N=C21 BJVCSICIEDHBNI-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 5
- NFNIRGPPIRJASP-UHFFFAOYSA-N 1-hydroxyquinolin-2-one Chemical compound C1=CC=C2C=CC(=O)N(O)C2=C1 NFNIRGPPIRJASP-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 150000005054 naphthyridines Chemical class 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical group ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052717 sulfur Chemical group 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000004212 difluorophenyl group Chemical group 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 3
- 229910052742 iron Inorganic materials 0.000 claims description 3
- 150000002828 nitro derivatives Chemical class 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Chemical group 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 claims description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
- 229910052804 chromium Inorganic materials 0.000 claims description 2
- 239000011651 chromium Substances 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 2
- 208000033641 Ring chromosome 5 syndrome Diseases 0.000 claims 1
- OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 claims 1
- ASWXNYNXAOQCCD-UHFFFAOYSA-N dichloro(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Cl)(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 ASWXNYNXAOQCCD-UHFFFAOYSA-N 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 claims 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 claims 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 abstract description 20
- 229910052736 halogen Inorganic materials 0.000 abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- 239000000243 solution Substances 0.000 description 40
- 239000000725 suspension Substances 0.000 description 33
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000007787 solid Substances 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 18
- 238000010992 reflux Methods 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 10
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- DRZOZPDZDAVSTP-UHFFFAOYSA-N ethyl 2-chloro-6,7-difluoroquinoline-3-carboxylate Chemical compound FC1=C(F)C=C2N=C(Cl)C(C(=O)OCC)=CC2=C1 DRZOZPDZDAVSTP-UHFFFAOYSA-N 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- DUDCRNHOLUWPDX-UHFFFAOYSA-N 1,8-naphthyridine-3-carboxamide Chemical compound N1=CC=CC2=CC(C(=O)N)=CN=C21 DUDCRNHOLUWPDX-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000002198 insoluble material Substances 0.000 description 6
- 239000000155 melt Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 239000004133 Sodium thiosulphate Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 5
- 235000019345 sodium thiosulphate Nutrition 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- ZDBVXHXVYPVPQT-UHFFFAOYSA-N 4,5-difluoro-2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC(F)=C(F)C=C1C=O ZDBVXHXVYPVPQT-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- RHBCLDOZGBHJFN-UHFFFAOYSA-N ethyl 6,7-difluoro-1-hydroxy-2-oxoquinoline-3-carboxylate Chemical compound FC1=C(F)C=C2N(O)C(=O)C(C(=O)OCC)=CC2=C1 RHBCLDOZGBHJFN-UHFFFAOYSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 150000004678 hydrides Chemical class 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 2
- NLEPLDKPYLYCSY-UHFFFAOYSA-N 2-fluoroquinoline Chemical compound C1=CC=CC2=NC(F)=CC=C21 NLEPLDKPYLYCSY-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000010908 decantation Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- MJSKHEBKBGTVLO-UHFFFAOYSA-N ethyl 6,7-difluoro-2-oxo-1h-quinoline-3-carboxylate Chemical compound FC1=C(F)C=C2NC(=O)C(C(=O)OCC)=CC2=C1 MJSKHEBKBGTVLO-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 150000003248 quinolines Chemical class 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- CGXLVFZJJOXEDF-UHFFFAOYSA-N 1,8-naphthyridine-3-carboxylic acid Chemical compound N1=CC=CC2=CC(C(=O)O)=CN=C21 CGXLVFZJJOXEDF-UHFFFAOYSA-N 0.000 description 1
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 1
- APKNYNUOFUOAGT-UHFFFAOYSA-N 2-chloro-1H-quinoline-2-carboxylic acid Chemical class ClC1(NC2=CC=CC=C2C=C1)C(=O)O APKNYNUOFUOAGT-UHFFFAOYSA-N 0.000 description 1
- ALWUTFXRAKXRNG-UHFFFAOYSA-N 2-chloro-6,7-difluoroquinoline-3-carboxylic acid Chemical compound FC1=C(F)C=C2N=C(Cl)C(C(=O)O)=CC2=C1 ALWUTFXRAKXRNG-UHFFFAOYSA-N 0.000 description 1
- OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 1
- JPHKMYXKNKLNDF-UHFFFAOYSA-N 3,4-difluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1F JPHKMYXKNKLNDF-UHFFFAOYSA-N 0.000 description 1
- WKXBEJYFYDYPNN-UHFFFAOYSA-N 3-aminoprop-1-en-1-one Chemical compound NCC=C=O WKXBEJYFYDYPNN-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- AZMDWRPTDCIFRD-UHFFFAOYSA-N 4-chloro-3-fluorobenzaldehyde Chemical compound FC1=CC(C=O)=CC=C1Cl AZMDWRPTDCIFRD-UHFFFAOYSA-N 0.000 description 1
- IDDIQDVSYHYORP-UHFFFAOYSA-N 6,7-difluoroquinoline Chemical compound C1=CN=C2C=C(F)C(F)=CC2=C1 IDDIQDVSYHYORP-UHFFFAOYSA-N 0.000 description 1
- LNRMNYOWYGXFBK-UHFFFAOYSA-N 6-fluoroquinoline-2-carboxylic acid Chemical compound C1=C(F)C=CC2=NC(C(=O)O)=CC=C21 LNRMNYOWYGXFBK-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 241000257303 Hymenoptera Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- SWJXWSAKHXBQSY-UHFFFAOYSA-N benzo(c)cinnoline Chemical compound C1=CC=C2C3=CC=CC=C3N=NC2=C1 SWJXWSAKHXBQSY-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- UKFXDFUAPNAMPJ-UHFFFAOYSA-N ethylmalonic acid Chemical compound CCC(C(O)=O)C(O)=O UKFXDFUAPNAMPJ-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical class C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical group CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000012521 purified sample Substances 0.000 description 1
- UWRGLMZRYNFMAB-UHFFFAOYSA-N pyrido[4,3-g]quinoline Chemical class C1=NC=CC2=CC3=CC=CN=C3C=C21 UWRGLMZRYNFMAB-UHFFFAOYSA-N 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/54—Three nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9304163A FR2703681B1 (fr) | 1993-04-08 | 1993-04-08 | Procede de preparation de fluoro-6-halogeno-2 quinoleine |
| FR9304163 | 1993-04-08 | ||
| FR9400391 | 1994-04-07 | ||
| PCT/FR1994/000391 WO1994024113A1 (fr) | 1993-04-08 | 1994-04-07 | Procede de preparation de fluoro-6 halogeno-2 quinoleine |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI954750A0 FI954750A0 (fi) | 1995-10-05 |
| FI954750L FI954750L (fi) | 1995-10-05 |
| FI113263B true FI113263B (fi) | 2004-03-31 |
Family
ID=9445879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI954750A FI113263B (fi) | 1993-04-08 | 1995-10-05 | Menetelmä 6-fluori-2-halogeenikinoliinin valmistamiseksi |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US5624933A (cs) |
| EP (1) | EP0693060B1 (cs) |
| JP (1) | JP3666753B2 (cs) |
| KR (1) | KR100330141B1 (cs) |
| AT (1) | ATE164155T1 (cs) |
| AU (1) | AU680493B2 (cs) |
| CA (1) | CA2158746C (cs) |
| CZ (1) | CZ283705B6 (cs) |
| DE (1) | DE69409101T2 (cs) |
| DK (1) | DK0693060T3 (cs) |
| ES (1) | ES2114189T3 (cs) |
| FI (1) | FI113263B (cs) |
| FR (1) | FR2703681B1 (cs) |
| GR (1) | GR3026401T3 (cs) |
| HU (1) | HU221861B1 (cs) |
| IL (1) | IL109255A (cs) |
| NO (1) | NO305752B1 (cs) |
| NZ (1) | NZ265072A (cs) |
| SK (1) | SK281139B6 (cs) |
| TW (1) | TW261612B (cs) |
| WO (1) | WO1994024113A1 (cs) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7510170B2 (en) | 2006-11-09 | 2009-03-31 | Guan Hong Enterprise Co., Ltd. | Humidifying fan |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1458205A (en) * | 1973-04-13 | 1976-12-08 | Pfizer | Fused pyrimidin-4- 3h-ones as antiallergy agents |
| US4190659A (en) * | 1973-08-27 | 1980-02-26 | Sandoz, Inc. | Pharmaceutical preparation and use of 4-hydroxy-2-quinolinone-3-carboxylic acid esters |
| US4710507A (en) * | 1983-12-22 | 1987-12-01 | Pfizer Inc. | Quinolone inotropic agents |
| DK111387A (da) * | 1986-03-05 | 1987-09-06 | Otsuka Pharma Co Ltd | Carbostyrilderivater og salte deraf, laegemiddel indeholdende saadanne derivater samt fremgangsmaade til fremstilling af derivaterne |
| DE3713672A1 (de) * | 1987-04-24 | 1988-11-17 | Bayer Ag | Verfahren zur herstellung von parenteral verabreichbaren chinoloncarbonsaeuren |
| NZ232092A (en) * | 1989-01-16 | 1992-05-26 | Bellon Labor Sa Roger | 8-halo-7-fluoro-4-oxo-1,4-dihydro-benzo(b)(1,8) naphthyridine-3-carboxylic acid esters and preparation thereof |
| NZ232090A (en) * | 1989-01-16 | 1990-12-21 | Bellon Labor Sa Roger | Halogen-containing 1-substituted-4-oxo-1,4-dihydro-benzo(b)(1,8)naphthyridine-3-carboxylic acid derivatives, preparation and pharmaceutical compositions thereof |
| NZ232091A (en) * | 1989-01-16 | 1990-12-21 | Bellon Labor Sa Roger | 7-fluoro-8-(piperazin-1-yl)-4-oxo-1,4-dihydro-benzo(b)(1,8)naphthyridine-3-carboxylic acid derivatives, preparation and pharmaceutical compositions thereof |
| US4948894A (en) * | 1989-02-21 | 1990-08-14 | American Cyanamid Company | 8-fluoro and 7, 8, 10-trifluoro-9-(substituted)-6-oxo-6H-benzo-(C)quinolizine-5-carboxylic acids |
| RO108347B1 (ro) * | 1989-10-30 | 1994-04-28 | Bellon Labor Sa Roger | DERIVATI DE BENZO-(b)-NAFTIRIDIN-1,8 SI PROCEDEU DE PREPARARE A ACESTORA |
| FR2682384B1 (fr) * | 1991-10-10 | 1995-04-07 | Bellon Laboratoires | Procede de preparation de benzo (b) naphtyridines. |
| FR2682378B1 (fr) * | 1991-10-10 | 1995-04-07 | Bellon Laboratoires | Nouveaux derives de l'acide fluoroquinoleine carboxylique-3 et leur preparation. |
-
1993
- 1993-04-08 FR FR9304163A patent/FR2703681B1/fr not_active Expired - Fee Related
-
1994
- 1994-04-07 IL IL10925594A patent/IL109255A/xx active IP Right Grant
- 1994-04-07 AU AU65408/94A patent/AU680493B2/en not_active Ceased
- 1994-04-07 CA CA002158746A patent/CA2158746C/fr not_active Expired - Fee Related
- 1994-04-07 DK DK94913146T patent/DK0693060T3/da active
- 1994-04-07 ES ES94913146T patent/ES2114189T3/es not_active Expired - Lifetime
- 1994-04-07 TW TW083103037A patent/TW261612B/zh active
- 1994-04-07 DE DE69409101T patent/DE69409101T2/de not_active Expired - Fee Related
- 1994-04-07 EP EP94913146A patent/EP0693060B1/fr not_active Expired - Lifetime
- 1994-04-07 HU HU9502934A patent/HU221861B1/hu not_active IP Right Cessation
- 1994-04-07 SK SK1256-95A patent/SK281139B6/sk unknown
- 1994-04-07 CZ CZ952600A patent/CZ283705B6/cs not_active IP Right Cessation
- 1994-04-07 JP JP52281694A patent/JP3666753B2/ja not_active Expired - Fee Related
- 1994-04-07 AT AT94913146T patent/ATE164155T1/de not_active IP Right Cessation
- 1994-04-07 NZ NZ265072A patent/NZ265072A/xx unknown
- 1994-04-07 KR KR1019950704416A patent/KR100330141B1/ko not_active Expired - Fee Related
- 1994-04-07 WO PCT/FR1994/000391 patent/WO1994024113A1/fr active IP Right Grant
- 1994-10-20 US US08/448,404 patent/US5624933A/en not_active Expired - Fee Related
-
1995
- 1995-10-02 NO NO953914A patent/NO305752B1/no unknown
- 1995-10-05 FI FI954750A patent/FI113263B/fi not_active IP Right Cessation
-
1998
- 1998-03-19 GR GR970402800T patent/GR3026401T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2071677A1 (en) | 7-isoindolinyl-quinolone- and -naphthyridonecarboxylic acid derivatives | |
| CZ10094A3 (en) | Derivatives of quinolonecarboxylic and naphthyridonecarboxylic acids | |
| Steinschifter et al. | Synthesis of oxazolo [4, 5‐c] quinolones by thermolytic degradation of 4‐azido‐2 (1H)‐quinolones | |
| DK161383B (da) | Quinolincarboxylsyre-derivat, fremgangsmaade til fremstilling heraf samt antibakterielle farmaceutiske praeparater indeholdende dette | |
| FI113263B (fi) | Menetelmä 6-fluori-2-halogeenikinoliinin valmistamiseksi | |
| FI104821B (fi) | Menetelmä bentso[b]naftyridiinijohdannaisten valmistamiseksi | |
| FI105400B (fi) | Uudet 3-karboksyylihappo-fluorikinoliinijohdannaiset, niiden valmistus ja niiden käyttö bentsonaftyridiinijohdannaisten valmistukseen | |
| WO2001034595A1 (fr) | Sels de metaux alcalins de derives de l'acide quinolinecarboxylique et procede de purification de ces derives au moyen de ces sels | |
| SK37394A3 (en) | 1,8-benzonaphthyridine derivatives, method of their preparation and compositions containing these derivatives | |
| SK123895A3 (en) | Derivatives of quinolone carboxylic and naphtyridone carboxylic acid, manufacturing process thereof, drugs containing same and their use | |
| JPH02247177A (ja) | ベンゾ［ｂ］［１，８］ナフチリジン誘導体類およびそれらの調製 | |
| CA2168921C (en) | 1,6-naphthyridonecarboxylic acid derivatives | |
| KR930000924B1 (ko) | 신규 1,4-디히드로-4-옥소퀴놀린 유도체 | |
| Rádl | Synthetic Studies Connected with the Preparation of 4-Cyclopropyl-7-fluoro-6-(4-methylpiperazin-1-yl)-1, 2, 4, 9-tetrahydrothiazolo [5, 4-b] quinoline-2, 9-dione | |
| FI93357B (fi) | 8-hydroksi-1-amino-4-okso-1,4-dihydro-3-kinoliinijohdannaisia | |
| JPH0413356B2 (cs) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |