NO318813B1 - (R)-1-Cyklopropyl-8-difluormetoksy-7-(1-metyl-2,3-dihydro-1H-5-isoindolyl)-4-okso-1,4-dihydro-3-kinolinkarboksylsyremetansulfonat,(R)-1-Cyklopropyl-8-difluormetoksy-7-(1-metyl-2,3-dihydro-1H-5-isoindolyl)-4-okso-1,4-dihydro-3-kinolinkarboksylsyremetansulfonatmonohydrat og blandinger inneholdende disse - Google Patents
(R)-1-Cyklopropyl-8-difluormetoksy-7-(1-metyl-2,3-dihydro-1H-5-isoindolyl)-4-okso-1,4-dihydro-3-kinolinkarboksylsyremetansulfonat,(R)-1-Cyklopropyl-8-difluormetoksy-7-(1-metyl-2,3-dihydro-1H-5-isoindolyl)-4-okso-1,4-dihydro-3-kinolinkarboksylsyremetansulfonatmonohydrat og blandinger inneholdende disse Download PDFInfo
- Publication number
- NO318813B1 NO318813B1 NO20002125A NO20002125A NO318813B1 NO 318813 B1 NO318813 B1 NO 318813B1 NO 20002125 A NO20002125 A NO 20002125A NO 20002125 A NO20002125 A NO 20002125A NO 318813 B1 NO318813 B1 NO 318813B1
- Authority
- NO
- Norway
- Prior art keywords
- dihydro
- added
- methyl
- mixture
- cyclopropyl
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 106
- IGTHEWGRXUAFKF-NVJADKKVSA-N 1-cyclopropyl-8-(difluoromethoxy)-7-[(1r)-1-methyl-2,3-dihydro-1h-isoindol-5-yl]-4-oxoquinoline-3-carboxylic acid;methanesulfonic acid;hydrate Chemical compound O.CS(O)(=O)=O.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 IGTHEWGRXUAFKF-NVJADKKVSA-N 0.000 title claims description 6
- -1 1-methyl-2,3-dihydro-1H-5-isoindolyl Chemical group 0.000 title description 18
- 239000004480 active ingredient Substances 0.000 claims abstract description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 12
- UPHLDCUEQOTSAD-RFVHGSKJSA-N 1-cyclopropyl-8-(difluoromethoxy)-7-[(1r)-1-methyl-2,3-dihydro-1h-isoindol-5-yl]-4-oxoquinoline-3-carboxylic acid;methanesulfonic acid Chemical compound CS(O)(=O)=O.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 UPHLDCUEQOTSAD-RFVHGSKJSA-N 0.000 claims description 5
- 239000005414 inactive ingredient Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 abstract description 19
- 150000003839 salts Chemical class 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 9
- 125000000217 alkyl group Chemical group 0.000 abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 7
- 125000005843 halogen group Chemical group 0.000 abstract description 6
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 5
- 125000003545 alkoxy group Chemical group 0.000 abstract 4
- 125000004414 alkyl thio group Chemical group 0.000 abstract 4
- 125000003118 aryl group Chemical group 0.000 abstract 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 4
- 125000003342 alkenyl group Chemical group 0.000 abstract 3
- 125000003277 amino group Chemical group 0.000 abstract 3
- 125000002252 acyl group Chemical group 0.000 abstract 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract 1
- 125000001118 alkylidene group Chemical group 0.000 abstract 1
- 239000003242 anti bacterial agent Substances 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 abstract 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 125000001841 imino group Chemical group [H]N=* 0.000 abstract 1
- 125000004043 oxo group Chemical group O=* 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 80
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- 239000013078 crystal Substances 0.000 description 55
- 238000004821 distillation Methods 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- 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 38
- 239000012044 organic layer Substances 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000002904 solvent Substances 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- 239000000725 suspension Substances 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- 229940098779 methanesulfonic acid Drugs 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 9
- 239000003480 eluent Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 7
- 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 7
- OIXMUQLVDNPHNS-UHFFFAOYSA-N methanesulfonic acid;hydrate Chemical compound O.CS(O)(=O)=O OIXMUQLVDNPHNS-UHFFFAOYSA-N 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- KWHZYHLFMXRMKD-SECBINFHSA-N 1-[(1r)-5-bromo-1-methyl-1,3-dihydroisoindol-2-yl]-2,2-dimethylpropan-1-one Chemical compound BrC1=CC=C2[C@@H](C)N(C(=O)C(C)(C)C)CC2=C1 KWHZYHLFMXRMKD-SECBINFHSA-N 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 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
- 239000000843 powder Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000012266 salt solution Substances 0.000 description 5
- FYELSNVLZVIGTI-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-5-ethylpyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1CC)CC(=O)N1CC2=C(CC1)NN=N2 FYELSNVLZVIGTI-UHFFFAOYSA-N 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 241000394605 Viola striata Species 0.000 description 4
- 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 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- WJYHCYBNUJVCEH-UHFFFAOYSA-N cyclohexane;ethoxyethane Chemical compound CCOCC.C1CCCCC1 WJYHCYBNUJVCEH-UHFFFAOYSA-N 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 4
- 230000000704 physical effect Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 4
- PFCRRGCZGUSSFY-UHFFFAOYSA-N 2,3-dihydro-1h-isoindol-5-ylboronic acid Chemical class OB(O)C1=CC=C2CNCC2=C1 PFCRRGCZGUSSFY-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 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 3
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- 229920002472 Starch Polymers 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
- WZICLKPREVGMFK-UHFFFAOYSA-N ethyl 2,4-dibromo-3-hydroxybenzoate Chemical compound CCOC(=O)C1=CC=C(Br)C(O)=C1Br WZICLKPREVGMFK-UHFFFAOYSA-N 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
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- 239000007924 injection Substances 0.000 description 3
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- 229910052763 palladium Inorganic materials 0.000 description 3
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- 239000008107 starch Substances 0.000 description 3
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- 239000000126 substance Substances 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- KTUCROBKAQWWPX-ZCFIWIBFSA-N (1r)-5-bromo-1-methyl-2,3-dihydro-1h-isoindole Chemical compound BrC1=CC=C2[C@@H](C)NCC2=C1 KTUCROBKAQWWPX-ZCFIWIBFSA-N 0.000 description 2
- TWYJGRVECRRQTM-FYZOBXCZSA-N (1r)-5-bromo-1-methyl-2,3-dihydro-1h-isoindole;hydrochloride Chemical compound Cl.BrC1=CC=C2[C@@H](C)NCC2=C1 TWYJGRVECRRQTM-FYZOBXCZSA-N 0.000 description 2
- JVCAVLWZRHPLJI-RXMQYKEDSA-N (3r)-6-bromo-3-methyl-2,3-dihydroisoindol-1-one Chemical compound BrC1=CC=C2[C@@H](C)NC(=O)C2=C1 JVCAVLWZRHPLJI-RXMQYKEDSA-N 0.000 description 2
- PRTXPVQMVXSGKQ-RFVHGSKJSA-N 1-cyclopropyl-8-(difluoromethoxy)-7-[(1r)-1-methyl-2,3-dihydro-1h-isoindol-5-yl]-4-oxoquinoline-3-carboxylic acid;hydrate Chemical compound O.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 PRTXPVQMVXSGKQ-RFVHGSKJSA-N 0.000 description 2
- LCESZCSHVYMHPV-RFVHGSKJSA-N 1-cyclopropyl-8-(difluoromethoxy)-7-[(1r)-1-methyl-2,3-dihydro-1h-isoindol-5-yl]-4-oxoquinoline-3-carboxylic acid;hydrochloride Chemical compound Cl.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 LCESZCSHVYMHPV-RFVHGSKJSA-N 0.000 description 2
- HBBKPRZFGXDWHG-SNVBAGLBSA-N 2,2-dimethyl-n-[(1r)-1-phenylethyl]propanamide Chemical compound CC(C)(C)C(=O)N[C@H](C)C1=CC=CC=C1 HBBKPRZFGXDWHG-SNVBAGLBSA-N 0.000 description 2
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 229940022663 acetate Drugs 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 229940007550 benzyl acetate Drugs 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- QUKGYYKBILRGFE-UHFFFAOYSA-N benzyloxyacetoaldehyde Natural products CC(=O)OCC1=CC=CC=C1 QUKGYYKBILRGFE-UHFFFAOYSA-N 0.000 description 2
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- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 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
- JDPLCOWWWBBRPJ-RFVHGSKJSA-M sodium;1-cyclopropyl-8-(difluoromethoxy)-7-[(1r)-1-methyl-2,3-dihydro-1h-isoindol-5-yl]-4-oxoquinoline-3-carboxylate Chemical compound [Na+].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 JDPLCOWWWBBRPJ-RFVHGSKJSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 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
- 238000010998 test method Methods 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
- 239000008215 water for injection 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
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
-
- 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
-
- 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
-
- 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
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- 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)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31137697 | 1997-10-27 | ||
| JP9280798 | 1998-03-20 | ||
| JP14058698 | 1998-05-07 | ||
| JP24482898 | 1998-08-31 | ||
| JP25365698 | 1998-09-08 | ||
| PCT/JP1998/004854 WO1999021849A1 (fr) | 1997-10-27 | 1998-10-27 | Procedes servant a preparer des derives 7-isoindolinequinolonecarboxyliques et leurs intermediaires, sels d'acides 7-isoindolinequinolonecarboxyliques, leurs hydrates, compositions les contenant en tant qu'ingredients actifs |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20002125D0 NO20002125D0 (no) | 2000-04-26 |
| NO20002125L NO20002125L (no) | 2000-06-07 |
| NO318813B1 true NO318813B1 (no) | 2005-05-09 |
Family
ID=27525611
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20002125A NO318813B1 (no) | 1997-10-27 | 2000-04-26 | (R)-1-Cyklopropyl-8-difluormetoksy-7-(1-metyl-2,3-dihydro-1H-5-isoindolyl)-4-okso-1,4-dihydro-3-kinolinkarboksylsyremetansulfonat,(R)-1-Cyklopropyl-8-difluormetoksy-7-(1-metyl-2,3-dihydro-1H-5-isoindolyl)-4-okso-1,4-dihydro-3-kinolinkarboksylsyremetansulfonatmonohydrat og blandinger inneholdende disse |
| NO20042109A NO20042109L (no) | 1997-10-27 | 2004-05-21 | Fremgangsmate for fremstilling av 7-isoindolinkinolonkarboksylsyre-derivater og mellomprodukter for disse, salter av 7-isoindolinkinolonkarboksylsyrer, hydrater derav, og |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20042109A NO20042109L (no) | 1997-10-27 | 2004-05-21 | Fremgangsmate for fremstilling av 7-isoindolinkinolonkarboksylsyre-derivater og mellomprodukter for disse, salter av 7-isoindolinkinolonkarboksylsyrer, hydrater derav, og |
Country Status (19)
| Country | Link |
|---|---|
| US (4) | US6337399B1 (pt) |
| EP (1) | EP1031569B1 (pt) |
| KR (2) | KR100611869B1 (pt) |
| CN (3) | CN1296369C (pt) |
| AT (1) | ATE461186T1 (pt) |
| AU (1) | AU750760B2 (pt) |
| CA (3) | CA2593381C (pt) |
| CY (1) | CY1110242T1 (pt) |
| DE (1) | DE69841563D1 (pt) |
| DK (1) | DK1031569T3 (pt) |
| ES (1) | ES2341509T3 (pt) |
| HK (1) | HK1030779A1 (pt) |
| HU (1) | HU229995B1 (pt) |
| IL (2) | IL135406A0 (pt) |
| NO (2) | NO318813B1 (pt) |
| NZ (1) | NZ504084A (pt) |
| PT (1) | PT1031569E (pt) |
| TW (2) | TW593308B (pt) |
| WO (1) | WO1999021849A1 (pt) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60128797D1 (de) | 2000-03-07 | 2007-07-19 | Ranbaxy Lab Ltd | EINTOPFSYNTHESE VON 3-CYCLOPROPYLAMINO-2- 2,4-DIBROMO-3-(DIFLUOROMETHOXY)BENZOYLö-2-PROPENSÄURE ALKYLESTER ALS NÜTZLICHES ZWISCHENPRODUKT FÜR ANTIBAKTERIELLE QUINOLON-ARZNEISTOFFE |
| 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 |
| EP1951663B1 (en) * | 2005-11-24 | 2016-07-20 | Dompé farmaceutici s.p.a. | (r)-arylkylamino derivatives and pharmaceutical compositions containing them |
| 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 |
| TWI583680B (zh) | 2011-08-31 | 2017-05-21 | 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 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE245638T1 (de) * | 1994-08-12 | 2003-08-15 | Toyama Chemical Co Ltd | Neue chinolon- oder naphthyridoncarbonsäurederivate oder deren salze |
| DE4431821A1 (de) * | 1994-09-07 | 1996-03-14 | Bayer Ag | Verfahren zur Herstellung von N-Arylaminoacrylsäurederivaten und die Verwendung so hergestellter N-Arylaminoacrylsäurederivate zur Herstellung von 4-Chinolon-3-carbonsäurederivaten |
| WO1997029102A1 (fr) * | 1996-02-09 | 1997-08-14 | Toyama Chemical Co., Ltd. | Derives de l'acide quinolonecarboxylique et leurs sels |
| JP4252282B2 (ja) * | 2001-11-06 | 2009-04-08 | 富山化学工業株式会社 | ２−［（１ｒ）−１−メチル−２−トリチル−２，３−ジヒドロ−１ｈ−５−イソインドリル］−１，３，６，２−ジオキサアザボロカンの非溶媒和物およびその製造法 |
-
1998
- 1998-10-27 KR KR1020057009280A patent/KR100611869B1/ko not_active IP Right Cessation
- 1998-10-27 US US09/529,407 patent/US6337399B1/en not_active Expired - Lifetime
- 1998-10-27 CN CNB2004100797208A patent/CN1296369C/zh not_active Expired - Lifetime
- 1998-10-27 AT AT98950405T patent/ATE461186T1/de active
- 1998-10-27 EP EP98950405A patent/EP1031569B1/en not_active Expired - Lifetime
- 1998-10-27 CN CNB988106272A patent/CN1195752C/zh not_active Expired - Lifetime
- 1998-10-27 CN CNA031603793A patent/CN1515555A/zh active Pending
- 1998-10-27 AU AU96486/98A patent/AU750760B2/en not_active Expired
- 1998-10-27 WO PCT/JP1998/004854 patent/WO1999021849A1/ja not_active Application Discontinuation
- 1998-10-27 CA CA2593381A patent/CA2593381C/en not_active Expired - Lifetime
- 1998-10-27 TW TW087117800A patent/TW593308B/zh not_active IP Right Cessation
- 1998-10-27 ES ES98950405T patent/ES2341509T3/es not_active Expired - Lifetime
- 1998-10-27 CA CA002307824A patent/CA2307824C/en not_active Expired - Lifetime
- 1998-10-27 IL IL13540698A patent/IL135406A0/xx active IP Right Grant
- 1998-10-27 DE DE69841563T patent/DE69841563D1/de not_active Expired - Lifetime
- 1998-10-27 KR KR1020007004509A patent/KR100565362B1/ko not_active IP Right Cessation
- 1998-10-27 CA CA002568251A patent/CA2568251A1/en not_active Abandoned
- 1998-10-27 HU HU0101766A patent/HU229995B1/hu unknown
- 1998-10-27 PT PT98950405T patent/PT1031569E/pt unknown
- 1998-10-27 TW TW093113303A patent/TWI242012B/zh not_active IP Right Cessation
- 1998-10-27 DK DK98950405.5T patent/DK1031569T3/da active
- 1998-10-27 NZ NZ504084A patent/NZ504084A/xx not_active IP Right Cessation
-
2000
- 2000-03-31 IL IL135406A patent/IL135406A/en not_active IP Right Cessation
- 2000-04-26 NO NO20002125A patent/NO318813B1/no not_active IP Right Cessation
-
2001
- 2001-03-12 HK HK01101736A patent/HK1030779A1/xx not_active IP Right Cessation
- 2001-09-25 US US09/961,364 patent/US6482835B2/en not_active Expired - Lifetime
-
2002
- 2002-08-01 US US10/209,078 patent/US20050203301A1/en not_active Abandoned
-
2004
- 2004-05-21 NO NO20042109A patent/NO20042109L/no not_active Application Discontinuation
-
2007
- 2007-03-27 US US11/691,740 patent/US7371868B2/en not_active Expired - Fee Related
-
2010
- 2010-06-11 CY CY20101100540T patent/CY1110242T1/el unknown
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