NO761926L - - Google Patents
Info
- Publication number
- NO761926L NO761926L NO761926A NO761926A NO761926L NO 761926 L NO761926 L NO 761926L NO 761926 A NO761926 A NO 761926A NO 761926 A NO761926 A NO 761926A NO 761926 L NO761926 L NO 761926L
- Authority
- NO
- Norway
- Prior art keywords
- optionally substituted
- hydrogen
- quinoline
- alkyl
- aralkyl
- Prior art date
Links
- -1 amino, hydroxy Chemical group 0.000 claims description 46
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 13
- 230000007062 hydrolysis Effects 0.000 claims description 12
- 238000006460 hydrolysis reaction Methods 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical class C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 claims description 7
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 239000007858 starting material Substances 0.000 claims description 5
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- 229910001854 alkali hydroxide Inorganic materials 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000004954 trialkylamino group Chemical group 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 claims description 2
- 239000000908 ammonium hydroxide Substances 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 2
- 125000005270 trialkylamine group Chemical group 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims 3
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 239000005864 Sulphur Chemical group 0.000 claims 1
- 239000001099 ammonium carbonate Substances 0.000 claims 1
- 235000012501 ammonium carbonate Nutrition 0.000 claims 1
- 150000003841 chloride salts Chemical class 0.000 claims 1
- 150000004679 hydroxides Chemical class 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- LJDZFAPLPVPTBD-UHFFFAOYSA-N nitroformic acid Chemical compound OC(=O)[N+]([O-])=O LJDZFAPLPVPTBD-UHFFFAOYSA-N 0.000 claims 1
- 150000007530 organic bases Chemical class 0.000 claims 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000013078 crystal Substances 0.000 description 11
- 238000000921 elemental analysis Methods 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000000155 melt Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- HLNJFEXZDGURGZ-UHFFFAOYSA-M 1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1 HLNJFEXZDGURGZ-UHFFFAOYSA-M 0.000 description 2
- UJIRBIMPTSELQD-UHFFFAOYSA-N 8-methyl-4-oxo-1h-quinoline-3-carboxylic acid Chemical compound N1C=C(C(O)=O)C(=O)C2=C1C(C)=CC=C2 UJIRBIMPTSELQD-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- KYGZCKSPAKDVKC-UHFFFAOYSA-N Oxolinic acid Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC2=C1OCO2 KYGZCKSPAKDVKC-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 150000003839 salts Chemical group 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- NDCFBPDNHOZORS-UHFFFAOYSA-N 1,2-dihydroquinoline-3-carboxylic acid Chemical compound C1=CC=C2NCC(C(=O)O)=CC2=C1 NDCFBPDNHOZORS-UHFFFAOYSA-N 0.000 description 1
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 description 1
- ZSEJADLCFCHIGX-UHFFFAOYSA-N 1-ethyl-4-oxoquinoline-3-carboxylic acid Chemical compound C1=CC=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 ZSEJADLCFCHIGX-UHFFFAOYSA-N 0.000 description 1
- YTWMJESCVWECIP-UHFFFAOYSA-N 1-ethyl-6-methoxy-4-oxo-3-quinolinecarboxylic acid Chemical compound COC1=CC=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 YTWMJESCVWECIP-UHFFFAOYSA-N 0.000 description 1
- MNLSUJGUPANTQB-UHFFFAOYSA-N 1-ethyl-7-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 MNLSUJGUPANTQB-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 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
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- RXXCIBALSKQCAE-UHFFFAOYSA-N 3-methylbutoxymethylbenzene Chemical compound CC(C)CCOCC1=CC=CC=C1 RXXCIBALSKQCAE-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-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
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- YVRGGPBWRTYCDP-UHFFFAOYSA-N 6-chloro-1-ethyl-4-oxoquinoline-3-carboxylic acid Chemical compound ClC1=CC=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 YVRGGPBWRTYCDP-UHFFFAOYSA-N 0.000 description 1
- HVEINHUJRQCZNZ-UHFFFAOYSA-N 6-nitro-4-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)C(C(=O)O)=CNC2=C1 HVEINHUJRQCZNZ-UHFFFAOYSA-N 0.000 description 1
- KSGSZGACXQALEU-UHFFFAOYSA-N 7-hydroxy-4-oxo-1h-quinoline-3-carboxylic acid Chemical compound OC1=CC=C2C(=O)C(C(=O)O)=CNC2=C1 KSGSZGACXQALEU-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- SNHCYVGJJIKKNG-UHFFFAOYSA-N 8-oxo-5h-[1,3]dioxolo[4,5-g]quinoline-7-carboxylic acid Chemical compound C1=C2C(=O)C(C(=O)O)=CNC2=CC2=C1OCO2 SNHCYVGJJIKKNG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005021 aminoalkenyl group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 125000004966 cyanoalkyl group Chemical group 0.000 description 1
- ZXIJMRYMVAMXQP-UHFFFAOYSA-N cycloheptene Chemical compound C1CCC=CCC1 ZXIJMRYMVAMXQP-UHFFFAOYSA-N 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- PYPCDUKQEIPHAF-UHFFFAOYSA-N diethyl 2-(anilinomethylidene)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)=CNC1=CC=CC=C1 PYPCDUKQEIPHAF-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-O hydron;quinoline Chemical compound [NH+]1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-O 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- AWJUIBRHMBBTKR-UHFFFAOYSA-O isoquinolin-2-ium Chemical compound C1=[NH+]C=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-O 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical compound CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 238000005956 quaternization reaction Methods 0.000 description 1
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000005208 trialkylammonium group Chemical group 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- 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
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Fremgangsmåte ved fremstilling av kinolin-3-carboxylsyrer.
Foreliggende oppfinnelse angår en fremgangsmåte ved fremstilling av kinolin-3-carboxylsyrer og derivater derav som har verdifulle antibakterielle egenskaper og derfor kan anvendes som plantevernmidler eller som medisiner i veterinær- og human-terapien.
Kinolin-3-carboxylsyrer og derivater derav representerer en meget viktig gruppe av forbindelsene med farmasøytisk anvendbarhet. ; l-alkyl-4-oxo-l,4_dihydro-kinolin-3-carboxylsyrer er verdifulle forbindelser som har antibakterielle egenskaper, og en av dem, nemlig 1-ethyl-6 , 7-methylendioxy -4-oxo-l ,4~dihydrokinolin-3-carboxylsyre (Journal of Medicinal Chemistry 11, l6o (1968) og britiske patenter nr. 1.076.828 og 3.287.458,).. har. allerede vært anvendt selv i terapien særlig for å helbrede urinveisinfeksjoner.
En rekke fremgangsmåter er tidligere kjent for fremstilling av forbindelsene av denne gruppe. I henhold til den ene variant ringsluttes dialkyl-anilino^methylen-malonat, hhv. derivater derav, og derved fåes alkyl-4-hydroxy-kinolin-3-carboxylater. Derefter blir disse forbindelser N-alkylert, estergruppen underkastes hydrolyse, og de erholdte 1-alkyl-4-oxo-l,4_dihydro-kinolin-3-carboxylsyrer opparbeides til antibakterielle preparater.
I henhold til en annen fremgangsmåte underkastes ethyl-2-(anilino-methylen)-acetoacetat en ringslutningsreaksjon, og derefter N-alkylering, og acetylgruppén på de dannede 3_acetyl-l-alkyl-4-oxo-1,4-dihydrokinolin-derivater omdannes til en carboxylgruppe ved en såkalt "haloform" reaksjon i nærvær av et halogen og en alkalihydroxydoppløsning (japanske patenter nr. 72.45-358 og 72.45.359). Reaksjonen fremgår av skjema B.
Den siste variant har en betraktelig fordel fremfor den tidligere som består i muligheten for anvendelse av den billigere aceteddikester for fremstilling av ethyl-2-(anilino-methylen)-acetacetat istedenfor diethylmalonat, som er utgangsmaterialet ved fremstilling av diethyl-anilino-methylen-malonat. På den annen side er det en alvorlig ulempe ved denne reaksjon med henblikk på industriell utnyttelse at på grunn av den dårlige oppløselighet av 3-acetyl-1-ethyl-4-oxo-1,4-dihydro-kinolin, kan reaksjonen bare ut-føres i heterofase, og derfor er de tilsiktede kinolin-3-carboxyl-syrer vanskelige å reprodusere og kan fåes i lave utbytter. Det har nu vist seg at 3-acylgruppen i 3-acyl-4-oxo-l,4-dihydrp-kinoliner kan overføres til en carboxylgruppe i en to-trinns fremgangsmåte som er lett å utføre også i stor skala. I det første trinn blir en "A"-kvartær forbindelse fremstilt i nærvær av jod og en aromatisk heterocyclisk forbindelse inneholdende nitrogen. Denne reaksjon er illustrert i skjema C.
Ved foreliggende oppfinnelse må hydrolysen av de kvartære
forbindelser beskyttes.
Foreliggende oppfinnelse angår en fremgangsmåte ved fremstilling av kinolin-3-carboxylsyrer med den generelle formel:
hvor R er hydrogen, eventuelt substituert alkyl.., eventuelt substituert alkenyl eller eventuelt substituert aralkyl; R1 er hydrogen, halogen, eventuelt substituert alkyl, eventuelt substituert, aryl, eventuelt substituert aralkyl, eventuelt substituert cycloalkyl, eventuelt substituert araino, hydroxy, eventuelt substituert alkoxy, eventuelt substituert aralkyloxy, eventuelt substituert acyl, nitro, carboxyl, et derivat av carboxyl eller en eventuelt substituert 5~ til 7-leddet heterocyclisk ring med 1 - 3 nitrogenatomer som er forbundet med kinolinringen over et av nitrogenene,
R 2 er hydrogen, halogen, eventuelt substituert alkyl, eventuelt substituert aralkyl, eventuelt substituert aryl, eventuelt substituert amino, nitro, hydroxyl, eventuelt substituert alkoxy, eventuelt substituert aralkyloxy, eller eventuelt substituert aryloxy;
R 3er hydrogen, halogen, eventuelt substituert alkyl, eventuelt substituert aralkyl, eventuelt substituert aryl, eventuelt substituert amino, hydroxyl, eventuelt substituert alkoxy, eller eventuelt substituert aryloxy; eller R 2 og RJ 3 kan sammen med 5,6-, 6,7- eller 7,8-sidene av kinolinringen danne en eventuelt substituert 5- til 7-leddet ring eventuelt inneholdende 1 eller 2 heteroatomer som kan være oxygen,
. svovel og/eller nitrogen; og .
nar n = 0, og R-<3>' er bundet til 8-stillingen av kinolinringen, kan R 3og R sammen danne en eventuelt substituert -(CH2)m-kjede, hvor m er 2, 3 eller 4;
X er oxygen eller svovel;
4
R er hydroxyl eller mercapto,
som omfatter å underkaste en forbindelse med den generelle formel:
hvor R er hydrogen, eventuelt substituert alkyl, eventuelt substituert aryl, eventuelt substituert aralkyl eller eventuelt substituert cycloalkyl, R^ er hydrogen, eventuelt substituert alkyl, eventuelt substituert aryl eller eventuelt substituert aralkyl;
Y er en aromatisk heterocyclisk ring inneholdende et tertiært nitrogen og bundet til ringen over nitrogenet eller en trialkyl-aminogruppe; og
Z er et anion,
hydrolyse.
Hydrolysen utføres fortrinnsvis i et alkalisk medium. Som basisk hydrolyseringsmiddel kan et alkalihydroxyd, f .eks. kal.ium-hydroxy.d , nat riumhydroxyd; et jordalkalimeta 1lhydroxyd, f.eks. calciumhydroxyd; ammoniumhydroxyd, eller de tilsvarende carbonater eller hydrocarbonater og et alkalisk sulfid, f.eks. natriumsulfid; et alkalisk bisulfid, f.eks. nat riumbisulfid anvendes.
Hydrolyse kan også utføres i et nøytralt eller surt medium,
i nærvær av et trialkylamin, fortrinnsvis triethylamin.
I nærvær av de ovenfor angitte hydrolyseringsmidler ut-føres hydrolysen fortrinnsvis i vann eller i nærvær av vann. og et med vann blandbart organisk oppløsningsmiddel, f.eks. ethanol, aceton, etc.
Temperaturen ved hydrolysen kan variere fra 0° til 300°C, men fortrinnsvis er den mellom 10° og 200°C.
Mineralsyren anvendt for surgjøring av reaksjonsblandingen er fortrinnsvis saltsyre, svovelsyre, eller som organisk syre kan fortrinnsvis maursyre eller eddiksyre anvendes.
Forbindelsen med den generelle formel I vil under hydrolysen eller efter at reaksjonsblandingen er surgjort, felles og kan fraskilles ved filtrering.
Uttrykket "eventuelt substituert alkyl" betegner fortrinnsvis en alkylgruppe, særlig methyl, ethyl, n-propyl, i-propyl;
en aminoalky lgruppe , særlig aminomethyl, 1-piperidy.lmethyl, 2-amino.ethyl; en hydroxyalkylgruppe, fortrinnsvis hydroxymethy 1, 1- hydroxyethyl, 2-hydroxyethyl; en halogenalkylgruppe, fortrinnsvis klormethyl, 2-klorethyl; eller en cyanoalkylgruppe, fortrinnsvis cyanomethyl.
Uttrykket "eventuelt substituert alkenyl" betegner fortrinnsvis en alkenylgruppe, fortrinnsvis allyl, vinyl; en amino-alkenylgruppe, fortrinnsvis 3-aminoallyl.
Uttrykket "eventuelt substituert aryl" betegner fortrinnsvis en arylgruppe, fortrinnsvis fenyl, 2-nafthyl, 2-pyridyl, 3-pyridyl, 4-pyridyl; aryl med 1 eller 2 subst it u.enter, fortrinnsvis 3,4-dimethylfenyl, 3,4-dimethoxyfenyl.
Uttrykket "eventuelt substituert aralkyl" betegner fortrinnsvis en aralkylgruppe, fortrinnsvis benzyl, 2-fenylethyl; en aralkylgruppe med 1 eller 2 substituenter, f.eks. (3,4-dimethylfenyl)-methyl, 2-(3,4-dimethoxy-fenyl)-ethy1.
Uttrykket "eventuelt substituert cycloalkyl" betegner fortrinnsvis en c.ycloalkylgruppe, fortrinnsvis cyclohexyl, cyclo-pentyl, cycloheptyl, cyclohexyl-methyl; en cycloalkylgruppe med 1 eller 2 substituenter., fortrinnsvis 2-hydroxy-cyclohexyl, 3-hydroxy-cyclohexyl, 4-hydroxy-cyclohexyl.
Uttrykket "halogen" er fortrinnsvis klor eller brom.
Uttrykket "eventuelt substituert alkoxy" betegner fortrinnsvis en alkoxygruppe, og særlig •■met hoxy , et hoxy, iso-butoxy, n-decyl-oxy, n-octyloxy, n-heptyloxy; en amino-.alkoxy gruppe, fortrinnsvis 2- amino-ethoxy, 2-(1-piperidyl)-ethoxy.
Uttrykket "eventuelt substituert aralkoxy" betegner fortrinnsvis en aralkoxygruppe, mere spesielt en benzyloxygruppe;
en aralkoxygruppe med 1 eller 2 substituenter, fortrinnsvis 4-methoxy-benzyl, 3,4-dimethoxy-benzyl, 3,4-methylendioxy-benzyl.
Uttrykket "eventuelt substituert acyl" betegner fortrinnsvis en acylgruppe, særlig formyl, acetyl, propionyl, benzoyl;
en acylgruppe med 1 eller 2 substituenter, fortrinnsvis hydroxy-acetyl, kloracetyl, aminoacetyl, (1-piperidyl)-acetyl, 3,4-dimethoxybenzoyl. "Carboxylsyrederivatgruppen" er fortrinnsvis en alkoxy-carbonylgruppe, fortrinnsvis methoxy-carbonyl, ethoxy-carbonyl, benzyloxy-carbonyl; en carboxylsyre-amidgruppe, spesielt carboxamid, N-ethyl-carboxamid, piperidyl-carbonyl, aziridinyl-carbonyl.
Uttrykket "eventuelt substituert 5- til 7-leddet heterocyclisk gruppe med 1-3 nitrogenatomer" betegner fortrinnsvis en heterocyclisk gruppe, mere spesielt pyrrolidinyl, piperazinyl, aziridinyl, pyrazolidinyl, imidazolidinyl, indolinyl , pyrrolinyl,-hexahydro-1,3,5-triazinyl, hexahydro-lH-azepinyl; en heterocyclisk gruppe med 1 eller 2 substituenter, fortrinnsvis 3-hydroxy-pyrrolidinyl, 3-acetoxy-pyrrolidinyl, 3-formyl-pyrrolidinyl, 3-benzyloxy-pyrrolidinyl, 4-methyl-piperazinyl, 4~ethyl-piperazinyl, 4-formyl-piperazinyl, 4-acetyl-piperazinyl, 4-benzyl-piperazinyl.
Gruppene R 2 og R 3 kan sammen med en 5,6-, 6,7- eller 7,8-side av kinolinringen danne en .benzen-, pyridin-, cyclohexen-, cyclopenten-, cyclphepten-, thiazol-, oxazol-, i.sothiazol-, isoxa-zol-, thiazolin-, isothiazolin-, oxazolin-, isoxazolin-, 1,3-dioxol-, 2 ,3-dihydro-l ,4-dioxen- eller 2 ,/f-H-l, 3-dioxenring , som eventuelt kan være substituert med 1 eller flere substituenter.
Som utgangsmaterialer kan de tilsvarende pyridinium-, kinolinium-, isokinolinium-, alkylsubstituert pyridinium- (fortrinns-, vis picolinium), kinaldinium- eller lepidinium-jodid, -bromid,
-perklorat, -sulfat, -fosfat eller -nitrat-kvartære salter av forbindelsene med den generelle formel II anvendes. Passende utgangsmaterialer er videre trialkylammoniumjodid, -bromid, -klorid, -perklorat, -sulfat, -fosfat eller -nit rat-kvartære salter, av forbindelsene med den generelle formel II.
Forbindelser med den generelle formel II er nye forbindelser, og kan fremstilles på følgende måte:
a) En forbindelse med den generelle formel:
hvor n, R, R<1>, R<2>, R<3>, R5, R6 og X er som ovenfor angitt, omsettes med en Y-aromatisk heterocyclisk forbindelse, inneholdende et tertiært nitrogenatom i nærvær av jod, eller.
b) en forbindelse med den generelle formel:
hvor n, R, R , R , R ,. R , R og X er som ovenfor angitt, og Z
betegner et halogénatom, i nærvær av et oppløsningsmiddel eller uten oppløsningsmiddel omsettes med en Y-aromatisk heterocyclisk forbindelse, med et tertiært nitrogenatom, eller med. et trialkyl-amino.
I kvaterneringsreaksjonen kan de konvensjonelt anvendte oppløsningsmidler, fortrinnsvis benzen, aceton, acetohitril, nitro-methan, dimethylformamid, etc., anvendes.
Videre fordeler ved foreliggende oppfinnelse vil fremgå av de følgende eksempler.
Eksempel . 1
2,32 g (5 mmol) l-ethyl-6,7-methylendioxy-4-oxo-l,4-dihydro -kinolin-3 -ca rbonyl -methyl -pyridinium jodid sprinkles i en oppløsning av 1 g natriumhydroxyd i 25 ml vann, og reaksjonsblandingen kokes i 1 time. Blandingen avkjøles, og pH innstilles på 1-2. De utfelte krystaller f rafiltreres, dekkes med vann, og tørres. 1,1 g (90%) 1-ethyl-6,7-methylendioxy-4-oxo-l,4-dihydro-kinolin-3-carboxylsyre fåes, som smelter ved 3l4°C(spaltning) efter omkrystallisåsjon fra dimethylformamid.
Elementæranalyse:
Eksempel 2
2,32 g (5 mmol) 1-ethy1-6,7-methylendioxy-4~oxo-1,4~dihydro-kinolin-3-carbonyl-methyl-pyridiniumjodid kokes i 25 ml vann i nærvær av 28 ml triethylamin i 16 timer. Derefter avkjøles oppløsningen til værelsetearperatur, og hensettes i flere dager.
De utfelte krystaller frafiltreres, dekkes med vann, og tørres. 1,1 g (85%) 1-ethyl-6,7-methylendioxy-4-oxo-1,4-dihydro-kinolin-3-carboxylsyre fåes, som smelter ved 313 - 3l4°C (spaltning) efter omkrystallisåsjon fra dimethylformamid. Produktet fra foreliggende eksempel gir ikke noen smeltepunktsnedsettelse ved blanding med produktet fra eksempel 1.
Eksempel 3
2,189(5 mmol) 6 , 7-methylendioxy-4,oxo-l ,4.-dihydro-kinolin-3-carbonyl-methyl-piperidiniumjodid kokes i 25 ml vann i nærvær av 1 g natriumhydroxyd i 1 time. Reaksjonsblandingen avkjøles til. værelsétemperatur, og pH innstilles på 1 - 2. De utfelte krystaller frafiltreres. Man får 1,0 g (86%) 6,7-methylendioxy-4-oxo-1,4-dihydro-kinolin-3-carboxylsyre, som smelter over 310°C.
Elementæranalyse:
Eksempel 4
2,17 g (5 mmol) 5,6,8-trimethyl-4-oxo-l,4-dihydro-kinolin-3-carbony.l-methyl-pyridinium jodid kokes i 25 ml vann i nærvær av 1 g natriumhydroxyd i 1 time.. Reaksjonsblandingen avkjøles til værelsetemperatur, og pH innstilles på 1 - 2. De utfelte krystaller frafiltreres , dekkes med vann og tørres. 1,10 g.(95%) 5,6,8-methyl-4-oxo-l,4-dihydro-kinolin-3-carboxylsyre fåes, som spalter ved 273 - 275°C.
Elementæranalyse:
Eksempel 5
2,31 g (5 mmol) l-ethyl-6-klor-4-oxo-l,4-dihydro-kinolin-3-carbonyl-methyl-pyridiniumjodid kokes i 25 ml vann i nærvær av 1 g natriumhydroxyd il time: Oppløsningen avkjøles til værelsetemperatur, og pH innstilles på 1 - 2. De utfelte krystaller f ra - filtreres, dekkes med vann og tørres. Man får 1,2 g (96%) 1-ethyl-6-klor-4-oxo-l,4-dihydro-kinolin-3-carboxylsyre, som smelter ved 235 - 237°C.
Elementæranalyse:
Eksempel 6
2,25 g (5 mmol) 1-ethyl-6-methoxy-4-oxo-l,4-dihydro-kinolin-3-carbonyl-raethyl-pyridiniumjodid kokes i 25 ml vann i nærvær av lg natriumhydroxyd i 1 time. Oppløsningen avkjøles til værelsetemperatur, og pH innstilles på 1 - 2 med en vandig oppløsning av hydrogenklorid. De utfelte krystaller frafiltreres, vaskes med vann og tørres. Man får 1,07 g (87,0%) 1-ethyl-6-methoxy-4-oxo-1,4-dihydro-kinolin-3-carboxylsyre, som smelter ved 222 - 223°C.
Elementæranalyse:
Eksempel 7
2,16 g (5 mmol) 1-et.hyl-7-methyl-4-oxo-l, 4-d'ihydro-kinolin-3-carbonyl-methyl-pyridiniumjodid kokes i .25 ml vann i nærvær av 1 g natriumcarbonat i 2 timer. Derefter innstilles oppløs-
ningens pH på 1 - 2 med eddiksyre. De utfelte krystaller frafiltreres, vaskes med vann og tørres. Man får 0,95 Q (80%) 1-ethyl-7-methyl-4-oxo-l,4-dihydro-kinolin-3-carboxylsyre, som smelter ved 285 .- 2'86°C.
Elementæranalyse:
Eksempel 8
2,10 g (5 mmol) l-ethyl-4-oxo-l,4~dihydro-kinolin-3-carbonyl-methyl-pyridiniumjodid kokes i 25 ml vann og 5 ml 34 vekt%-ig natriumhydroxyd i 1 time.Reaksjonsblandingen av-kjøles til værelsetemperatur, og pH innstilles på 1 - 2. De utfelte krystaller frafiltreres, vaskes med vann og tørres. Man får 0,90 g (83%) l-ethyl-4-oxo-l,4-dihydro-kinolin-3-carboxylsyre, som smelter ved 251 - 252°C.
Elementæranalyse:
Eksempel 9
2,039(5 mmol) 8-met hy1-4-oxo-1,4-dihydro-kinolin-3-carbonyl-methyl-pyridiniumjodid kokes i 25.ml vann, i nærvær av lg natriumhydroxyd i 1 time. Oppløsningen avkjøles til værelsetemperatur, og pH innstilles på 1 - 2. De utfelte krystaller frafiltreres, vaskes med vann og tørres. Man får 0,90 g (89%) 8~methyl-4-oxo-l,4-dihydro-kinolin-3-carboxylsyre, som spaltes ved 276 - 277°C.
Elementæranalyse:
Eksempel 10
2,15 g (5 mmol) 6-nitro-4-oxo-l ,4-dihydro-kinolin-3-carbonyl-.. methyl-pyridiniumjodid kokes i 25 ml vann i nærvær av 1 g natriumhydroxyd i 1 time. Oppløsningen avkjøles til værelsetemperatur,. og PH innstilles på .1 - 2. De utfelte krystaller f raf ilt reres , vaskes med vann og tørres. Man får 1,15 g (98%) 6-nitro-4-oxo-l,4-dihydro-kinolin-3-carboxylsyre, som smelter ved 283 - 284°C.
Elementæranalyse:
Eksempel 11
1,02 g (2,5 mmol) 7-hydroxy-4-oxo-1,4-dihydro-kinolin-3-carbonyl-methyl-pyridiniumjodid kokes i 15 ml vann i nærvær av
0,5 g natriumhydroxyd. Oppløsningen avkjøles til værelsetempera-. tur, og pH innstilles på 1 - 2. De utfelte krystaller frafiltreres, vaskes med vann og tørres. Man får 0,50 g (98%) 7-hydroxy-4-oxo-l,4-dihydro-kinolin-3-carboxylsyre, som smelter ved 242 -244°c.
Elementæranalyse:
Claims (7)
1. Fremgangsmåte ved fremstilling av kinolin-3-carboxylsyrer med den generelle formel: •
hvor R er hydrogen, eventuelt substituert alkyl, eventuelt substituert' alkenyl eller eventuelt substituert aralkyl; R"1" er hydrogen, halogen, eventuelt substituert alkyl, eventuelt substituert aryl, ^eventuelt substituert aralkyl, eventuelt substituert cycloalkyl, eventuelt substituert amino, hydroxy, eventuelt substituert alkoxy, eventuelt substituert aralkyloxy, eventuelt substituert acyl, nitro, carboxylsyre, et carboxylsyrederivat eller en eventuelt substituert 5- til 7-leddet heterocyclisk ring med 1 3 nitrogener, som er bundet til kinolinringen over nitrogenet;
2 R . er hydrogen, halogen, eventuelt substituert alkyl, eventuelt substituert aralkyl, eventuelt substituert aryl, eventuelt substituert amino, nitro, hydroxylj eventuelt substituert alkoxy,
eventuelt substituert aralkyloxy, eller eventuelt substituert aryloxy; R 3 er hydrogen, halogen, eventuelt substituert • alkyl, eventuelt substituert aralkyl, eventuelt substituert aryl, eventuelt substituert amino, hydroxyl, eventuelt substituert alkoxy eller eventuelt substituert aryloxy, eller
R 2 og RJ 3 kan sammen med 5,6-, 6,7- eller 7,8-sidene av kinolinringen danne en eventuelt substituert, 5- til 7-leddet ring med 1 eller 2 heteroatomer som kan være oxygen, svovel eller nitrogen;
o 3
nar n er 0 og R er bundet til 8-stillingen av kinolinringen, kan R3 og R sammen danne en.eventuelt substituert -(CH2 )m -ring, hvor m er 2, 3 eller 4;
X er hydrogen eller svovel-, R <4> er hydroxyl eller mercapto, karakterisert ved at en forbindelse med den generelle formel:
hvor n, R, R , R , R og X er som ovenfor angxtt; ,?:<?.
5 • •}' < ■■ R er hydrogen, eventuelt substituert alkyl, eventuelt substituert aryl, eventuelt substituert aralkyl eller eventuelt substituert cycloalkyl;
R 6 er hydrogen, eventuelt substituert alkyl, eventuelt substituert aryl, eller eventuelt substituert aralkyl;
Y er en aromatisk heterocyclisk ring inneholdende et tertiært nitrogen, som er bundet over nitrogenet eller en trialkylamino-gruppe; og
Z er et anion,
underkastes hydrolyse.
2. Fremgangsmåte ifølge krav 1,
karakterisert ved . at hydrolysen utføres i nærvær av hydroxyder, carbonater eller hydrocarbonater, eller organiske baser.
3. Fremgangsmåte ifølge krav 1 eller 2, karakterisert ved at hydrolysen utføres i nærvær av ammoniumhydroxyd, et alkali- eller jordalkalimetallhydroxyd, ammoniumcarbonat, et alkali- eller jordalkalicarbonat, et alkali-hydrocarbonat eller trialkylamin.
4- Fremgangsmåte ifølge krav 1 - 3,
karakterisert ved at hydrolysen utføres mellom 0° og 300°C, fortrinnsvis mellom 10° og 200°C.
5. ' Fremgangsmåte ifølge krav 1 - 4, karakterisert ved at man anvender jodid-, bromid- eller kloridsaltet av en forbindelse med den generelle formel I som utgangsmateriale for fremstilling av en kinolin-3-carboxylsyre med den generelle formel I.
6. Fremgangsmåte ifølge krav 1-5, karakterisert ved at der anvendes en forbindelse med formel II hvor er hydrogen eller alkyl, og R^ er
hydrogen eller alkyl.
7. Fremgangsmåte ifølge krav 1-6, karakterisert ved at der som utgangsmateriale anvendes 1 -et hy 1-6 , 7-methyleridioxy-4_oxo -1,4-dihydro-kino linn-ea rbonyl-methy1-pyridiniumjodid, -klorid eller -bromid.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU75CI00001585A HU170951B (hu) | 1975-06-06 | 1975-06-06 | Novyj sposob poluchenija hinolin-3-karbonovykh kislot |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO761926L true NO761926L (no) | 1976-12-07 |
Family
ID=10994570
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO761926A NO761926L (no) | 1975-06-06 | 1976-06-04 |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS51146476A (no) |
| DK (1) | DK247976A (no) |
| ES (1) | ES448619A1 (no) |
| FI (1) | FI761583A (no) |
| GB (1) | GB1502405A (no) |
| HU (1) | HU170951B (no) |
| NO (1) | NO761926L (no) |
| SE (1) | SE7606308L (no) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5540616A (en) * | 1978-09-14 | 1980-03-22 | Otsuka Pharmaceut Co Ltd | Preparation of benzo-hetero-compound |
| JPS58105965A (ja) * | 1981-12-15 | 1983-06-24 | Nippon Shinyaku Co Ltd | 置換キノリンカルボン酸誘導体 |
| JPS61143363A (ja) * | 1984-12-17 | 1986-07-01 | Kyorin Pharmaceut Co Ltd | キノロンカルボン酸誘導体の製造方法 |
| JPS61143364A (ja) * | 1984-12-17 | 1986-07-01 | Kyorin Pharmaceut Co Ltd | キノロンカルボン酸誘導体の製造方法 |
| DE3705621C2 (de) * | 1986-02-25 | 1997-01-09 | Otsuka Pharma Co Ltd | Heterocyclisch substituierte Chinoloncarbonsäurederivate |
| JPS6483068A (en) * | 1987-09-25 | 1989-03-28 | Otsuka Pharma Co Ltd | Production of benzo-heterocyclic compound |
| EP0748799B1 (en) * | 1994-03-01 | 2002-09-11 | Ishihara Sangyo Kaisha, Ltd. | Process for producing 5,7-dichloro-4-hydroxyquinoline |
-
1975
- 1975-06-06 HU HU75CI00001585A patent/HU170951B/hu unknown
-
1976
- 1976-06-03 SE SE7606308A patent/SE7606308L/xx not_active Application Discontinuation
- 1976-06-04 NO NO761926A patent/NO761926L/no unknown
- 1976-06-04 FI FI761583A patent/FI761583A/fi not_active Application Discontinuation
- 1976-06-04 GB GB23285/76A patent/GB1502405A/en not_active Expired
- 1976-06-04 DK DK247976A patent/DK247976A/da not_active Application Discontinuation
- 1976-06-05 ES ES448619A patent/ES448619A1/es not_active Expired
- 1976-06-07 JP JP51065718A patent/JPS51146476A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DK247976A (da) | 1976-12-07 |
| ES448619A1 (es) | 1977-07-01 |
| FI761583A (no) | 1976-12-07 |
| GB1502405A (en) | 1978-03-01 |
| SE7606308L (sv) | 1976-12-07 |
| HU170951B (hu) | 1977-10-28 |
| JPS51146476A (en) | 1976-12-16 |
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