KR100611869B1 - 7-이소인돌린-퀴놀론 카복실산 유도체 및 그 중간체의제조방법 및 7-이소인돌린-퀴놀론 카복실산 유도체의 염,그의 수화물 및 이들을 활성성분으로 함유하는 조성물 - Google Patents
7-이소인돌린-퀴놀론 카복실산 유도체 및 그 중간체의제조방법 및 7-이소인돌린-퀴놀론 카복실산 유도체의 염,그의 수화물 및 이들을 활성성분으로 함유하는 조성물 Download PDFInfo
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- KR100611869B1 KR100611869B1 KR1020057009280A KR20057009280A KR100611869B1 KR 100611869 B1 KR100611869 B1 KR 100611869B1 KR 1020057009280 A KR1020057009280 A KR 1020057009280A KR 20057009280 A KR20057009280 A KR 20057009280A KR 100611869 B1 KR100611869 B1 KR 100611869B1
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- Prior art keywords
- formula
- salt
- reaction
- compound
- dihydro
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- 150000003839 salts Chemical class 0.000 title claims abstract description 234
- 238000000034 method Methods 0.000 title claims description 27
- 239000002253 acid Substances 0.000 title claims description 8
- 239000000203 mixture Substances 0.000 title abstract description 46
- 239000000543 intermediate Substances 0.000 title abstract description 8
- 150000004677 hydrates Chemical class 0.000 title abstract description 7
- 239000004480 active ingredient Substances 0.000 title abstract description 5
- 150000007513 acids Chemical class 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 66
- 125000006239 protecting group Chemical group 0.000 claims abstract description 36
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 23
- 125000005843 halogen group Chemical group 0.000 claims abstract description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 20
- -1 halogenated formic acid ester Chemical class 0.000 claims description 173
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 11
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 10
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 10
- 150000001298 alcohols Chemical class 0.000 claims description 8
- 238000007363 ring formation reaction Methods 0.000 claims description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 239000001569 carbon dioxide Substances 0.000 claims description 5
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 5
- 238000006722 reduction reaction Methods 0.000 claims description 5
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 4
- 238000005885 boration reaction Methods 0.000 claims description 4
- 229910052796 boron Inorganic materials 0.000 claims description 4
- 238000005658 halogenation reaction Methods 0.000 claims description 3
- CEROEJJKQHMTSL-UHFFFAOYSA-N 2,3-dihydro-1h-indol-5-ylboronic acid Chemical class OB(O)C1=CC=C2NCCC2=C1 CEROEJJKQHMTSL-UHFFFAOYSA-N 0.000 claims 1
- 241000283690 Bos taurus Species 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 21
- 125000003545 alkoxy group Chemical group 0.000 abstract description 13
- 239000004599 antimicrobial Substances 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 description 202
- 238000006243 chemical reaction Methods 0.000 description 118
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 95
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- 239000002904 solvent Substances 0.000 description 75
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- 239000012044 organic layer Substances 0.000 description 65
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 64
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 51
- 239000013078 crystal Substances 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 49
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 34
- 238000002360 preparation method Methods 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- 239000002585 base Substances 0.000 description 32
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 30
- 229910052763 palladium Inorganic materials 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
- 238000001816 cooling Methods 0.000 description 24
- NJDRXTDGYFKORP-LLVKDONJSA-N garenoxacin Chemical compound N([C@@H](C1=CC=2)C)CC1=CC=2C(C=1OC(F)F)=CC=C(C(C(C(O)=O)=C2)=O)C=1N2C1CC1 NJDRXTDGYFKORP-LLVKDONJSA-N 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 21
- 229910052751 metal Inorganic materials 0.000 description 21
- 239000002184 metal Substances 0.000 description 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 20
- 238000010992 reflux Methods 0.000 description 19
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 230000002411 adverse Effects 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 125000003277 amino group Chemical group 0.000 description 17
- 239000012046 mixed solvent Substances 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 150000001408 amides Chemical class 0.000 description 16
- 150000002170 ethers Chemical class 0.000 description 16
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 15
- 239000003054 catalyst Substances 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 150000002940 palladium Chemical class 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- 229940098779 methanesulfonic acid Drugs 0.000 description 13
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 150000003462 sulfoxides Chemical class 0.000 description 12
- 125000003342 alkenyl group Chemical group 0.000 description 11
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 11
- 150000008282 halocarbons Chemical class 0.000 description 11
- OIXMUQLVDNPHNS-UHFFFAOYSA-N methanesulfonic acid;hydrate Chemical compound O.CS(O)(=O)=O OIXMUQLVDNPHNS-UHFFFAOYSA-N 0.000 description 11
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- 235000017550 sodium carbonate Nutrition 0.000 description 11
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 125000004414 alkyl thio group Chemical group 0.000 description 10
- 239000012456 homogeneous solution Substances 0.000 description 10
- 150000002825 nitriles Chemical class 0.000 description 10
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
- 239000008096 xylene Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- 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 9
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 8
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 238000002955 isolation Methods 0.000 description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 8
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 8
- 230000000704 physical effect Effects 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 7
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 7
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 7
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 229910052744 lithium Inorganic materials 0.000 description 7
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 7
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 7
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 7
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 6
- QDTAWQSYHADTLC-UHFFFAOYSA-N 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1h-isoindole Chemical compound C=1C=C2C(C)NCC2=CC=1B1OC(C)(C)C(C)(C)O1 QDTAWQSYHADTLC-UHFFFAOYSA-N 0.000 description 6
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 229940019778 diethylene glycol diethyl ether Drugs 0.000 description 6
- ZVUUANRFLJIZGV-UHFFFAOYSA-N ethyl 7-bromo-1-cyclopropyl-8-(difluoromethoxy)-4-oxoquinoline-3-carboxylate Chemical compound C12=C(OC(F)F)C(Br)=CC=C2C(=O)C(C(=O)OCC)=CN1C1CC1 ZVUUANRFLJIZGV-UHFFFAOYSA-N 0.000 description 6
- 230000002140 halogenating effect Effects 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 239000011261 inert gas Substances 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 239000011777 magnesium Substances 0.000 description 6
- 229910052749 magnesium Inorganic materials 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 5
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 5
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 5
- 229930040373 Paraformaldehyde Natural products 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 5
- 150000001735 carboxylic acids Chemical class 0.000 description 5
- 235000015165 citric acid Nutrition 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 150000007522 mineralic acids Chemical class 0.000 description 5
- ZLUNJWQJXQFSAM-SECBINFHSA-N n-[(1r)-1-(4-bromophenyl)ethyl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)N[C@H](C)C1=CC=C(Br)C=C1 ZLUNJWQJXQFSAM-SECBINFHSA-N 0.000 description 5
- 229920002866 paraformaldehyde Polymers 0.000 description 5
- 239000003444 phase transfer catalyst Substances 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
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- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
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- 239000000463 material Substances 0.000 description 1
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- 150000004681 metal hydrides Chemical class 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
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- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
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- 125000002757 morpholinyl group Chemical group 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- 125000006126 n-butyl sulfonyl group Chemical group 0.000 description 1
- 125000006124 n-propyl sulfonyl group Chemical group 0.000 description 1
- 125000005185 naphthylcarbonyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 150000002896 organic halogen compounds Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
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- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- WVUCPRGADMCTBN-UHFFFAOYSA-M potassium;3-ethoxy-3-oxopropanoate Chemical compound [K+].CCOC(=O)CC([O-])=O WVUCPRGADMCTBN-UHFFFAOYSA-M 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- RNMAVYVRUNMYCN-UHFFFAOYSA-N quinoline-3-carboxylic acid hydrate Chemical compound O.N1=CC(=CC2=CC=CC=C12)C(=O)O RNMAVYVRUNMYCN-UHFFFAOYSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005930 sec-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- DVQHRBFGRZHMSR-UHFFFAOYSA-N sodium methyl 2,2-dimethyl-4,6-dioxo-5-(N-prop-2-enoxy-C-propylcarbonimidoyl)cyclohexane-1-carboxylate Chemical compound [Na+].C=CCON=C(CCC)[C-]1C(=O)CC(C)(C)C(C(=O)OC)C1=O DVQHRBFGRZHMSR-UHFFFAOYSA-N 0.000 description 1
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical class [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- DDFYFBUWEBINLX-UHFFFAOYSA-M tetramethylammonium bromide Chemical compound [Br-].C[N+](C)(C)C DDFYFBUWEBINLX-UHFFFAOYSA-M 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- 238000006177 thiolation reaction Methods 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- 238000002525 ultrasonication Methods 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
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/48—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
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- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
T-3811의 염 | pH | 용해도(㎍/㎖) |
메탄설폰산염 | 3.66 | 16510 |
인산염 | 3.29 | 8520 |
L-락트산염 | 4.40 | 1980 |
나트륨염 | 10.11 | 2340 |
시트르산염 | 3.90 | 420 |
아세트산염 | 4.22 | 6230 |
염산염 | 3.99 | 5450 |
마그네슘염 | 7.58 | 60 |
황산염 | 3.46 | 1170 |
Claims (8)
- 하기 화학식 10의 페닐알킬아민 유도체 또는 그의 염을 염기의 존재하에 이산화탄소, 할로겐화 포름산 에스테르 또는 탄산 에스테르와 반응시켜 하기 화학식 9의 2-아미노알킬 벤조산 유도체 또는 그의 염을 수득하고, 이어서 할로겐화 반응에 도입하여 하기 화학식 8의 2-아미노알킬-5-할로게노벤조산 유도체 또는 그의 염을 수득하고, 이어서 환원반응에 도입하여 하기 화학식 6의 2-아미노알킬-5-할로게노벤질알콜 유도체 또는 그의 염을 수득한 후, 폐환반응에 도입하여 하기 화학식 4a의 1-알킬-5-할로게노이소인돌린 유도체 또는 그의 염을 수득하고, 이어서 붕산화반응에 도입함을 특징으로 하는, 하기 화학식 2b의 1-알킬이소인돌린-5-붕소산 유도체 또는 그의 염의 제조방법:화학식 2b화학식 4a상기 식에서,R4a는 알킬기이고;R5a는 아미노 보호기, 치환되거나 비치환된 알킬, 사이클로알킬, 알킬설포닐, 아릴설포닐, 아실 또는 아릴기이고;R5는 수소 원자, 아미노 보호기, 치환되거나 비치환된 알킬, 사이클로알킬, 알킬설포닐, 아릴설포닐, 아실 또는 아릴기이고;R10은 수소 원자 또는 카복실 보호기이고;X1은 할로겐 원자이고;R8 및 R9는 수소 원자 또는 저급 알킬기이거나, 또는 함께 붕소 원자를 함유하는 환을 형성한다.
- 제 1 항에 있어서,R4a가 저급 알킬기이고, R5a가 아미노 보호기이고, R5가 수소 원자 또는 아미노 보호기인 제조방법.
- 하기 화학식 10의 페닐알킬아민 유도체 또는 그의 염을 염기의 존재하에 이산화탄소, 할로겐화 포름산 에스테르 또는 탄산 에스테르와 반응시켜 하기 화학식 9의 2-아미노알킬 벤조산 유도체 또는 그의 염을 수득하고, 이어서 할로겐화 반응에 도입하여 하기 화학식 8의 2-아미노알킬-5-할로게노벤조산 유도체 또는 그의 염을 수득하고, 이어서 폐환반응에 도입하여 하기 화학식 7의 1-알킬-3-옥소-5-할로게노이소인돌린 유도체 또는 그의 염을 수득하고, 이어서 환원반응에 도입하여 하기 화학식 4a의 1-알킬-5-할로게노이소인돌린 유도체 또는 그의 염을 수득한 후, 붕산화반응에 도입함을 특징으로 하는, 하기 화학식 2b의 1-알킬이소인돌린-5-붕소산 유도체 또는 그의 염의 제조방법:화학식 2b화학식 4a화학식 8화학식 9화학식 10상기 식에서,R4a는 알킬기이고;R5a는 아미노 보호기, 치환되거나 비치환된 알킬, 사이클로알킬, 알킬설포닐, 아릴설포닐, 아실 또는 아릴기이고;R5는 수소 원자, 아미노 보호기, 치환되거나 비치환된 알킬, 사이클로알킬, 알킬설포닐, 아릴설포닐, 아실 또는 아릴기이고;R10은 수소 원자 또는 카복실 보호기이고;X1은 할로겐 원자이고;R8 및 R9는 수소 원자 또는 저급 알킬기이거나, 또는 함께 붕소 원자를 함유하는 환을 형성한다.
- 제 3 항에 있어서,R4a가 저급 알킬기이고, R5a가 아미노 보호기이고, R5가 수소 원자 또는 아미노 보호기인 제조방법.
- 삭제
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JP31137697 | 1997-10-27 | ||
JPJP-P-1997-00311376 | 1997-10-27 | ||
JP9280798 | 1998-03-20 | ||
JPJP-P-1998-00092807 | 1998-03-20 | ||
JPJP-P-1998-00140586 | 1998-05-07 | ||
JP14058698 | 1998-05-07 | ||
JP24482898 | 1998-08-31 | ||
JPJP-P-1998-00244828 | 1998-08-31 | ||
JPJP-P-1998-00253656 | 1998-09-08 | ||
JP25365698 | 1998-09-08 | ||
KR1020007004509A KR100565362B1 (ko) | 1997-10-27 | 1998-10-27 | 7-이소인돌린-퀴놀론 카복실산 유도체 및 그 중간체의 제조방법 및 7-이소인돌린-퀴놀론 카복실산 유도체의 염, 그의 수화물 및 이들을 활성성분으로 함유하는 조성물 |
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KR1020007004509A KR100565362B1 (ko) | 1997-10-27 | 1998-10-27 | 7-이소인돌린-퀴놀론 카복실산 유도체 및 그 중간체의 제조방법 및 7-이소인돌린-퀴놀론 카복실산 유도체의 염, 그의 수화물 및 이들을 활성성분으로 함유하는 조성물 |
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US (4) | US6337399B1 (ko) |
EP (1) | EP1031569B1 (ko) |
KR (2) | KR100611869B1 (ko) |
CN (3) | CN1296369C (ko) |
AT (1) | ATE461186T1 (ko) |
AU (1) | AU750760B2 (ko) |
CA (3) | CA2593381C (ko) |
CY (1) | CY1110242T1 (ko) |
DE (1) | DE69841563D1 (ko) |
DK (1) | DK1031569T3 (ko) |
ES (1) | ES2341509T3 (ko) |
HK (1) | HK1030779A1 (ko) |
HU (1) | HU229995B1 (ko) |
IL (2) | IL135406A0 (ko) |
NO (2) | NO318813B1 (ko) |
NZ (1) | NZ504084A (ko) |
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KR100763077B1 (ko) * | 2000-03-07 | 2007-10-04 | 랜박시 래보러터리스 리미티드 | 항균 퀴놀론 약제용으로 유용한 중간 물질로서의 알킬 3-시클로프로필아미노-2-[2,4-디브로모-3-(디플루오로메톡시)벤조일]-2-프로페노에이트의 원-포트 합성 방법 |
DE10111262A1 (de) * | 2001-03-09 | 2002-09-12 | Studiengesellschaft Kohle Mbh | Verfahren zur Herstellung von Vinyl- Aryl- und Heteroarylessigsäuren und ihrer Devivate |
US6777420B2 (en) | 2001-06-15 | 2004-08-17 | Microbiotix, Inc. | Heterocyclic antibacterial compounds |
JP2006151808A (ja) * | 2002-12-24 | 2006-06-15 | Dai Ichi Seiyaku Co Ltd | 抗菌性水性製剤 |
US20090156577A1 (en) * | 2004-09-09 | 2009-06-18 | Benjamin Davis | 7-amino alkylidenyl-heterocyclic quinolones and naphthyridones |
ES2597843T3 (es) * | 2005-11-24 | 2017-01-23 | Dompé Farmaceutici S.P.A. | Derivados de (R)-arilalquilamino y composiciones farmacéuticas que los contienen |
US7902227B2 (en) * | 2007-07-27 | 2011-03-08 | Janssen Pharmaceutica Nv. | C-7 isoxazolinyl quinolone / naphthyridine derivatives useful as antibacterial agents |
CN101298418B (zh) * | 2008-06-13 | 2010-12-15 | 江苏康鹏农化有限公司 | 3-氧代-3-(2,4-二卤代-3-二氟甲氧基苯基)丙酸乙酯的制备方法 |
JP5921826B2 (ja) * | 2010-06-30 | 2016-05-24 | 富山化学工業株式会社 | 5−ブロモ−2−(1−置換エチル)安息香酸エステルの新規製造法 |
TW201718506A (zh) | 2011-08-31 | 2017-06-01 | 大塚製藥股份有限公司 | 喹啉酮化合物 |
WO2013121439A2 (en) * | 2012-02-15 | 2013-08-22 | Glenmark Generics Limited | Process for garenoxacin mesylate |
CN105837555B (zh) * | 2016-03-31 | 2019-01-25 | 南京华威医药科技集团有限公司 | 加雷沙星及其中间体制备方法 |
CN105777631B (zh) * | 2016-04-18 | 2018-06-29 | 浙江中欣氟材股份有限公司 | 一种1-环丙基-4-氧代-7-溴-8-二氟甲氧基-1,4-二氢喹啉-3-羧酸乙酯的合成方法 |
CN105801482B (zh) * | 2016-04-18 | 2018-06-22 | 浙江中欣氟材股份有限公司 | 一种1-环丙基-4-氧代-7-溴-8-二氟甲氧基-1,4-二氢喹啉-3-羧酸乙酯的制备方法 |
CN106957255B (zh) * | 2017-03-28 | 2018-01-09 | 上海馨远医药科技有限公司 | 一种(R)‑N‑Boc‑5‑溴‑1‑甲基异吲哚啉及其制备方法和应用 |
CN112028816B (zh) * | 2020-09-11 | 2022-10-14 | 江阴迈康升华医药科技有限公司 | 一种取代异吲哚啉的合成方法 |
CN114105790A (zh) * | 2021-12-14 | 2022-03-01 | 无锡捷化医药科技有限公司 | 一种3-氨基-4,5-二溴苯甲酸甲酯的制备方法 |
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