CA2181351C - Procede et intermediaires destines a la preparation de sels d'acide naphtyridonecarboxylique - Google Patents
Procede et intermediaires destines a la preparation de sels d'acide naphtyridonecarboxyliqueInfo
- Publication number
- CA2181351C CA2181351C CA002181351A CA2181351A CA2181351C CA 2181351 C CA2181351 C CA 2181351C CA 002181351 A CA002181351 A CA 002181351A CA 2181351 A CA2181351 A CA 2181351A CA 2181351 C CA2181351 C CA 2181351C
- Authority
- CA
- Canada
- Prior art keywords
- formula
- compound
- acid
- alkyl
- treating
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 47
- 239000002253 acid Substances 0.000 title claims abstract description 36
- 150000003839 salts Chemical class 0.000 title abstract description 11
- 239000000543 intermediate Substances 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 116
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 22
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 19
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 239000003638 chemical reducing agent Substances 0.000 claims description 14
- 229910052751 metal Inorganic materials 0.000 claims description 14
- 239000002184 metal Substances 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 239000012380 dealkylating agent Substances 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 239000007868 Raney catalyst Substances 0.000 claims description 7
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 7
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 7
- 125000001246 bromo group Chemical group Br* 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 6
- ZFDWWDZLRKHULH-UHFFFAOYSA-N 1,2-dimethyl-5,6-dihydro-4h-pyrimidine Chemical compound CN1CCCN=C1C ZFDWWDZLRKHULH-UHFFFAOYSA-N 0.000 claims description 5
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical group CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 claims description 5
- 229910052725 zinc Inorganic materials 0.000 claims description 5
- 239000011701 zinc Substances 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000005984 hydrogenation reaction Methods 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 229910000510 noble metal Inorganic materials 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 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 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000002516 radical scavenger Substances 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- -1 naphthyridone carboxylic acid Chemical class 0.000 abstract description 5
- ZFRUGZMCGCYBRC-UHFFFAOYSA-N 1h-1,8-naphthyridin-2-one Chemical compound C1=CC=NC2=NC(O)=CC=C21 ZFRUGZMCGCYBRC-UHFFFAOYSA-N 0.000 abstract description 4
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 4
- 230000003115 biocidal effect Effects 0.000 abstract description 4
- 239000003242 anti bacterial agent Substances 0.000 abstract description 3
- 229940088710 antibiotic agent Drugs 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000002002 slurry Substances 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- 229940125898 compound 5 Drugs 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 238000002390 rotary evaporation Methods 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 229910052684 Cerium Inorganic materials 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000005233 alkylalcohol group Chemical group 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 229910052792 caesium Inorganic materials 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- MKRBAPNEJMFMHU-UHFFFAOYSA-N 1-benzylpyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1CC1=CC=CC=C1 MKRBAPNEJMFMHU-UHFFFAOYSA-N 0.000 description 1
- SVDDJQGVOFZBNX-UHFFFAOYSA-N 2-chloroethyl carbonochloridate Chemical compound ClCCOC(Cl)=O SVDDJQGVOFZBNX-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- VSCBATMPTLKTOV-UHFFFAOYSA-N 2-tert-butylimino-n,n-diethyl-1,3-dimethyl-1,3,2$l^{5}-diazaphosphinan-2-amine Chemical compound CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C VSCBATMPTLKTOV-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- DWSNAPIQHSSSFW-UHFFFAOYSA-N FC(F)F.CC1=CC=C(S(O)(=O)=O)C=C1 Chemical class FC(F)F.CC1=CC=C(S(O)(=O)=O)C=C1 DWSNAPIQHSSSFW-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 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 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 229910017974 NH40H Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical group [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical class FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 1
- DNPRVXJGNANVCZ-UHFFFAOYSA-N bromo(nitro)methane Chemical compound [O-][N+](=O)CBr DNPRVXJGNANVCZ-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- JLSXYCZRMYCIMY-UHFFFAOYSA-N ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylate Chemical compound C12=NC(Cl)=C(F)C=C2C(=O)C(C(=O)OCC)=CN1C1=CC=C(F)C=C1F JLSXYCZRMYCIMY-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- BSUHUYNJLGMEPD-UHFFFAOYSA-N methanol;propan-1-ol Chemical compound OC.CCCO BSUHUYNJLGMEPD-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000012420 spiking experiment Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
L'invention se rapporte à de nouveaux procédés de préparation de composés de la formule (I), dans laquelle R?1¿H est tel que ci-défini, un sel de l'antibiotique à base de naphtyridone, l'acide 7-(1.alpha.,5.alpha.,6.alpha.)-(6-amino-3-azabicyclo[3,1,0]hex-3-yl)-1-(2,4-difluorophényl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphtyridine-3-carboxylique, ainsi qu'un acide pharmaceutiquement acceptable. Ce sel et ces antibiotiques présentent une activité antibactérienne. L'invention se rapporte également à de nouveaux intermédiaires des formules (IIIA), (IIIB) et (IV),ainsi qu'à des procédés destinés à leur préparation. Les composés des formules (IIIA), (IIIB) et (IV) sont aptes à être utilisés comme intermédiaires dans les synthèses des sels d'acide alcanesulfonique/d'acide azabicyclo naphtyridonecarboxylique de la formule (I).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18194294A | 1994-01-18 | 1994-01-18 | |
| US08/181,942 | 1994-01-18 | ||
| PCT/IB1994/000410 WO1995019361A1 (fr) | 1994-01-18 | 1994-12-12 | Procede et intermediaires destines a la preparation de sels d'acide naphtyridonecarboxylique |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2181351A1 CA2181351A1 (fr) | 1995-07-20 |
| CA2181351C true CA2181351C (fr) | 1999-09-28 |
Family
ID=22666458
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002181351A Expired - Fee Related CA2181351C (fr) | 1994-01-18 | 1994-12-12 | Procede et intermediaires destines a la preparation de sels d'acide naphtyridonecarboxylique |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP0740667A1 (fr) |
| JP (1) | JP2891543B2 (fr) |
| KR (1) | KR100221386B1 (fr) |
| CN (1) | CN1141634A (fr) |
| AU (1) | AU694149B2 (fr) |
| BR (1) | BR9408490A (fr) |
| CA (1) | CA2181351C (fr) |
| CZ (1) | CZ286896B6 (fr) |
| FI (1) | FI962880A7 (fr) |
| HU (1) | HUT74883A (fr) |
| IL (1) | IL112323A (fr) |
| MY (1) | MY130510A (fr) |
| NO (1) | NO305838B1 (fr) |
| NZ (1) | NZ276478A (fr) |
| PL (1) | PL179996B1 (fr) |
| RU (1) | RU2147303C1 (fr) |
| TW (1) | TW414791B (fr) |
| WO (1) | WO1995019361A1 (fr) |
| ZA (1) | ZA95340B (fr) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996039406A1 (fr) * | 1995-06-06 | 1996-12-12 | Pfizer Inc. | NOUVELLE FORME DE CRISTAL DE SEL ANHYDRE D'ACIDE METHANE-SULFONIQUE ET D'ACIDE 7-([1α, 5α, 6α]-6-AMINO-3-AZABICYCLO[3.1.0]HEX-3-YL)-6-FLUORO-1-(2,4-DIFLUOROPHENYL)-1,4-DIHYDRO-4-OXO-1,8-NAPHTYRIDINE-3 CARBOXYLIQUE |
| ES2095809B1 (es) * | 1995-07-27 | 1997-12-16 | Sint Quimica Sa | Procedimiento para la preparacion de acidos naftiridin carboxilicos y sus sales. |
| GB9524466D0 (en) * | 1995-11-30 | 1996-01-31 | Pfizer Ltd | Process |
| JPH1087617A (ja) * | 1996-07-09 | 1998-04-07 | Pfizer Inc | キノリン系抗生物質の合成に有用な中間体の製法 |
| GB9614422D0 (en) * | 1996-07-09 | 1996-09-04 | Pfizer Ltd | Novel process |
| HN1998000106A (es) | 1997-08-01 | 1999-01-08 | Pfizer Prod Inc | Composiciones parenterales de alatroflaxacino |
| US6114531A (en) * | 1998-07-28 | 2000-09-05 | Pfizer Inc. | Process for preparing quinolone and naphthyridone carboxylic acids |
| HN1999000141A (es) * | 1998-09-03 | 2000-06-19 | Pfizer Prod Inc | Procedimiento para preparar sales de trovafloxacina de adicion de acidos. |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5164402A (en) * | 1989-08-16 | 1992-11-17 | Pfizer Inc | Azabicyclo quinolone and naphthyridinone carboxylic acids |
| US5256791A (en) | 1992-03-02 | 1993-10-26 | Pfizer Inc. | Preparation of intermediates in the synthesis of quinoline antibiotics |
-
1994
- 1994-12-12 EP EP95901569A patent/EP0740667A1/fr not_active Withdrawn
- 1994-12-12 NZ NZ276478A patent/NZ276478A/en unknown
- 1994-12-12 WO PCT/IB1994/000410 patent/WO1995019361A1/fr not_active Ceased
- 1994-12-12 CZ CZ19962111A patent/CZ286896B6/cs not_active IP Right Cessation
- 1994-12-12 PL PL94317043A patent/PL179996B1/pl unknown
- 1994-12-12 CN CN94194842A patent/CN1141634A/zh active Pending
- 1994-12-12 AU AU10754/95A patent/AU694149B2/en not_active Ceased
- 1994-12-12 HU HU9601957A patent/HUT74883A/hu unknown
- 1994-12-12 BR BR9408490A patent/BR9408490A/pt not_active Application Discontinuation
- 1994-12-12 KR KR1019960703846A patent/KR100221386B1/ko not_active Expired - Fee Related
- 1994-12-12 RU RU96115919A patent/RU2147303C1/ru active
- 1994-12-12 JP JP7518931A patent/JP2891543B2/ja not_active Expired - Lifetime
- 1994-12-12 CA CA002181351A patent/CA2181351C/fr not_active Expired - Fee Related
- 1994-12-17 TW TW083111804A patent/TW414791B/zh not_active IP Right Cessation
-
1995
- 1995-01-12 IL IL11232395A patent/IL112323A/en not_active IP Right Cessation
- 1995-01-17 ZA ZA95340A patent/ZA95340B/xx unknown
- 1995-01-17 MY MYPI95000103A patent/MY130510A/en unknown
-
1996
- 1996-07-17 FI FI962880A patent/FI962880A7/fi unknown
- 1996-07-17 NO NO962990A patent/NO305838B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| KR100221386B1 (ko) | 1999-09-15 |
| WO1995019361A1 (fr) | 1995-07-20 |
| BR9408490A (pt) | 1997-08-26 |
| AU1075495A (en) | 1995-08-01 |
| NO962990L (no) | 1996-07-17 |
| CN1141634A (zh) | 1997-01-29 |
| PL179996B1 (en) | 2000-11-30 |
| EP0740667A1 (fr) | 1996-11-06 |
| RU2147303C1 (ru) | 2000-04-10 |
| HU9601957D0 (en) | 1996-09-30 |
| FI962880A0 (fi) | 1996-07-17 |
| FI962880A7 (fi) | 1996-07-17 |
| JPH09501182A (ja) | 1997-02-04 |
| CA2181351A1 (fr) | 1995-07-20 |
| IL112323A (en) | 2001-03-19 |
| MY130510A (en) | 2007-06-29 |
| JP2891543B2 (ja) | 1999-05-17 |
| NO305838B1 (no) | 1999-08-02 |
| CZ286896B6 (en) | 2000-07-12 |
| PL317043A1 (en) | 1997-03-03 |
| TW414791B (en) | 2000-12-11 |
| ZA95340B (en) | 1996-07-17 |
| NZ276478A (en) | 1998-05-27 |
| AU694149B2 (en) | 1998-07-16 |
| CZ211196A3 (en) | 1997-01-15 |
| IL112323A0 (en) | 1995-03-30 |
| HUT74883A (en) | 1997-02-28 |
| NO962990D0 (no) | 1996-07-17 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |