CN1037180C - 抗微生物的碳代青霉烯衍生物的制备方法 - Google Patents
抗微生物的碳代青霉烯衍生物的制备方法 Download PDFInfo
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- CN1037180C CN1037180C CN93104412A CN93104412A CN1037180C CN 1037180 C CN1037180 C CN 1037180C CN 93104412 A CN93104412 A CN 93104412A CN 93104412 A CN93104412 A CN 93104412A CN 1037180 C CN1037180 C CN 1037180C
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- alkyl group
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- 238000002360 preparation method Methods 0.000 title claims description 211
- 230000000845 anti-microbial effect Effects 0.000 title description 9
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical class C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 242
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 113
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 341
- -1 Carbamoyloxy group Chemical group 0.000 claims description 281
- 125000000217 alkyl group Chemical group 0.000 claims description 243
- 125000004432 carbon atom Chemical group C* 0.000 claims description 172
- 229910052760 oxygen Inorganic materials 0.000 claims description 106
- 239000001301 oxygen Substances 0.000 claims description 106
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 100
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 99
- 125000001424 substituent group Chemical group 0.000 claims description 90
- 238000000034 method Methods 0.000 claims description 71
- 238000006243 chemical reaction Methods 0.000 claims description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 56
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 54
- 125000005843 halogen group Chemical group 0.000 claims description 50
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 47
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 45
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000003342 alkenyl group Chemical group 0.000 claims description 27
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
- 125000000304 alkynyl group Chemical group 0.000 claims description 22
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 17
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000001589 carboacyl group Chemical group 0.000 claims description 13
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 11
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 10
- 125000004423 acyloxy group Chemical group 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 4
- 150000001450 anions Chemical group 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 25
- 229910052717 sulfur Inorganic materials 0.000 claims 11
- 125000004434 sulfur atom Chemical group 0.000 claims 11
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 8
- 125000003277 amino group Chemical group 0.000 claims 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
- FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 claims 1
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims 1
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 102000003850 Dipeptidase 1 Human genes 0.000 abstract description 6
- 108090000204 Dipeptidase 1 Proteins 0.000 abstract description 6
- 239000003242 anti bacterial agent Substances 0.000 abstract description 5
- 229940088710 antibiotic agent Drugs 0.000 abstract description 5
- 125000004185 ester group Chemical group 0.000 abstract description 5
- 208000015181 infectious disease Diseases 0.000 abstract description 2
- 230000000813 microbial effect Effects 0.000 abstract description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 abstract 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 1
- 239000002585 base Substances 0.000 description 406
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 302
- 150000001721 carbon Chemical group 0.000 description 269
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 249
- 239000000203 mixture Substances 0.000 description 222
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 193
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 164
- 239000005864 Sulphur Chemical group 0.000 description 150
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 148
- 239000000243 solution Substances 0.000 description 134
- 238000000862 absorption spectrum Methods 0.000 description 119
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 117
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 114
- 238000006722 reduction reaction Methods 0.000 description 108
- 230000009467 reduction Effects 0.000 description 106
- 238000009834 vaporization Methods 0.000 description 106
- 230000008016 vaporization Effects 0.000 description 106
- 235000002639 sodium chloride Nutrition 0.000 description 103
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 97
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 82
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 78
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 71
- 239000007864 aqueous solution Substances 0.000 description 70
- 239000012141 concentrate Substances 0.000 description 68
- 235000008504 concentrate Nutrition 0.000 description 68
- 239000000843 powder Substances 0.000 description 64
- 239000011541 reaction mixture Substances 0.000 description 59
- 238000003756 stirring Methods 0.000 description 58
- 238000001035 drying Methods 0.000 description 54
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 52
- 238000001228 spectrum Methods 0.000 description 51
- 238000005481 NMR spectroscopy Methods 0.000 description 47
- 238000004821 distillation Methods 0.000 description 46
- 239000002904 solvent Substances 0.000 description 44
- VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 40
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 40
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 40
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 36
- 238000005984 hydrogenation reaction Methods 0.000 description 36
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 34
- 238000010898 silica gel chromatography Methods 0.000 description 33
- 235000010334 sodium propionate Nutrition 0.000 description 31
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 31
- 239000004324 sodium propionate Substances 0.000 description 30
- 229960003212 sodium propionate Drugs 0.000 description 30
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 29
- 239000010410 layer Substances 0.000 description 29
- 239000011780 sodium chloride Substances 0.000 description 29
- 229960002668 sodium chloride Drugs 0.000 description 29
- BDIIXJCOXLQTKD-UHFFFAOYSA-N azetidin-1-amine Chemical compound NN1CCC1 BDIIXJCOXLQTKD-UHFFFAOYSA-N 0.000 description 28
- 239000003054 catalyst Substances 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- 238000005406 washing Methods 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 24
- 235000017557 sodium bicarbonate Nutrition 0.000 description 24
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 24
- 239000002994 raw material Substances 0.000 description 22
- 230000002829 reductive effect Effects 0.000 description 22
- 239000011259 mixed solution Substances 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 20
- 239000000706 filtrate Substances 0.000 description 19
- 239000012299 nitrogen atmosphere Substances 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- 239000012071 phase Substances 0.000 description 15
- 238000010790 dilution Methods 0.000 description 14
- 239000012895 dilution Substances 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 238000010025 steaming Methods 0.000 description 13
- 230000008020 evaporation Effects 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 11
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 11
- 238000000605 extraction Methods 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- NHDXHOZRFJCGQV-NPGWBMRXSA-N COC1=CC=C(CS[C@H]2C[C@H](N(C2)C(=O)OC(C2=CC=CC=C2)C(=O)OCC2=CC=C(C=C2)[N+](=O)[O-])C(=O)O)C=C1 Chemical compound COC1=CC=C(CS[C@H]2C[C@H](N(C2)C(=O)OC(C2=CC=CC=C2)C(=O)OCC2=CC=C(C=C2)[N+](=O)[O-])C(=O)O)C=C1 NHDXHOZRFJCGQV-NPGWBMRXSA-N 0.000 description 10
- 239000003513 alkali Substances 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 230000008030 elimination Effects 0.000 description 10
- 238000003379 elimination reaction Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 238000010908 decantation Methods 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 8
- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical class COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 8
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 6
- 125000003710 aryl alkyl group Chemical group 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 238000005342 ion exchange Methods 0.000 description 6
- 231100000989 no adverse effect Toxicity 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical compound OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 5
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 5
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 5
- 125000002905 alkanoylamido group Chemical group 0.000 description 5
- 125000003368 amide group Chemical group 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 5
- 238000004140 cleaning Methods 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 125000004043 oxo group Chemical group O=* 0.000 description 5
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- WIHIUTUAHOZVLE-UHFFFAOYSA-N 1,3-diethoxypropan-2-ol Chemical compound CCOCC(O)COCC WIHIUTUAHOZVLE-UHFFFAOYSA-N 0.000 description 4
- 125000006017 1-propenyl group Chemical group 0.000 description 4
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- QPQGTZMAQRXCJW-UHFFFAOYSA-N [chloro(phenyl)phosphoryl]benzene Chemical class C=1C=CC=CC=1P(=O)(Cl)C1=CC=CC=C1 QPQGTZMAQRXCJW-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- RJCQBQGAPKAMLL-UHFFFAOYSA-N bromotrifluoromethane Chemical class FC(F)(F)Br RJCQBQGAPKAMLL-UHFFFAOYSA-N 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methylcyclopentane Chemical compound CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 4
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 description 4
- 125000005429 oxyalkyl group Chemical group 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 229920002554 vinyl polymer Polymers 0.000 description 4
- 150000003952 β-lactams Chemical class 0.000 description 4
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
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- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
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- 125000001400 nonyl 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])[H] 0.000 description 1
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- 125000002958 pentadecyl 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])[H] 0.000 description 1
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- DPLVEEXVKBWGHE-UHFFFAOYSA-N potassium sulfide Chemical compound [S-2].[K+].[K+] DPLVEEXVKBWGHE-UHFFFAOYSA-N 0.000 description 1
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- 125000004079 stearyl 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])C([H])([H])C([H])([H])[H] 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000002889 tridecyl 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])[H] 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/10—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D477/12—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6
- C07D477/16—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6 with hetero atoms or carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 3
- C07D477/20—Sulfur atoms
-
- 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
-
- 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
-
- 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)
- 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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP52163/92 | 1992-03-11 | ||
| JP5216392 | 1992-03-11 | ||
| JP244953/92 | 1992-09-14 | ||
| JP24495392 | 1992-09-14 | ||
| JP24657892 | 1992-09-16 | ||
| JP246578/92 | 1992-09-16 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1079472A CN1079472A (zh) | 1993-12-15 |
| CN1037180C true CN1037180C (zh) | 1998-01-28 |
Family
ID=27294566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93104412A Expired - Fee Related CN1037180C (zh) | 1992-03-11 | 1993-03-11 | 抗微生物的碳代青霉烯衍生物的制备方法 |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP0560613B1 (enExample) |
| KR (1) | KR100258225B1 (enExample) |
| CN (1) | CN1037180C (enExample) |
| AT (1) | ATE173733T1 (enExample) |
| AU (1) | AU664422B2 (enExample) |
| CA (1) | CA2091486A1 (enExample) |
| CZ (1) | CZ290002B6 (enExample) |
| DE (1) | DE69322188T2 (enExample) |
| DK (1) | DK0560613T3 (enExample) |
| ES (1) | ES2125945T3 (enExample) |
| FI (1) | FI103046B (enExample) |
| HU (1) | HU218676B (enExample) |
| IL (1) | IL105020A (enExample) |
| MX (1) | MX9301361A (enExample) |
| NO (1) | NO303730B1 (enExample) |
| NZ (1) | NZ247129A (enExample) |
| RU (1) | RU2097383C1 (enExample) |
| TW (1) | TW249803B (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI101226B1 (fi) * | 1991-06-04 | 1998-05-15 | Sankyo Co | Menetelmä lääkeaineena käyttökelpoisten 2-[2-(karbonyyli)pyrrolidin-4-yylitio]-6-(1-hydroksietyyli)-1-metyylikarbapen-2-eemi-3-karboksyylihappojohdannaisten valmistamiseksi |
| GB9515975D0 (en) | 1995-08-04 | 1995-10-04 | Zeneca Ltd | Chemical compounds |
| EP0882728B1 (en) * | 1995-12-21 | 2002-09-04 | Sankyo Company Limited | 1-methylcarbapenem derivatives |
| WO1997041123A1 (en) * | 1996-04-26 | 1997-11-06 | Sankyo Company, Limited | 1-methylcarbapenem derivatives |
| AU4020897A (en) | 1996-08-17 | 1998-03-06 | Zeneca Limited | 3-mercaptopyrrolidines as farnesyl protein transferase inhibitors |
| WO2000034282A1 (en) * | 1998-12-07 | 2000-06-15 | Sankyo Company, Limited | 1-methylcarbapenem derivatives |
| US7041660B2 (en) | 1999-07-06 | 2006-05-09 | Sankyo Company, Limited | Crystalline 1-methylcarbapenem derivatives |
| GB9930318D0 (en) | 1999-12-22 | 2000-02-09 | Zeneca Ltd | Novel compounds |
| GB9930317D0 (en) | 1999-12-22 | 2000-02-09 | Zeneca Ltd | Novel compounds |
| KR100628676B1 (ko) * | 2001-09-26 | 2006-09-27 | 머크 앤드 캄파니 인코포레이티드 | 카바페넴 화합물의 제조방법 |
| WO2005063704A1 (ja) * | 2003-12-25 | 2005-07-14 | Ono Pharmaceutical Co., Ltd. | アゼチジン環化合物およびその医薬 |
| CN101367814B (zh) * | 2007-06-28 | 2010-12-15 | 山东轩竹医药科技有限公司 | 被巯基吡咯烷甲酰哌啶取代的培南衍生物 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0442497A1 (en) * | 1990-02-14 | 1991-08-21 | Sumitomo Pharmaceuticals Company, Limited | Novel beta-lactam compounds and their production |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1283906C (en) * | 1983-05-09 | 1991-05-07 | Makoto Sunagawa | .beta.-LACTAM COMPOUNDS AND PRODUCTION THEREOF |
| DE3780344T2 (de) * | 1986-03-27 | 1993-01-28 | Sumitomo Pharma | Beta-lactam-verbindungen und deren herstellung. |
| CA2036941A1 (en) * | 1990-02-23 | 1991-08-24 | Isao Kawamoto | Carbapenem derivatives having antibiotic activity, their preparation and their use |
| GB9107363D0 (en) * | 1991-04-08 | 1991-05-22 | Ici Plc | Antibiotic compounds |
| FI101226B1 (fi) * | 1991-06-04 | 1998-05-15 | Sankyo Co | Menetelmä lääkeaineena käyttökelpoisten 2-[2-(karbonyyli)pyrrolidin-4-yylitio]-6-(1-hydroksietyyli)-1-metyylikarbapen-2-eemi-3-karboksyylihappojohdannaisten valmistamiseksi |
| US5608056A (en) * | 1992-04-13 | 1997-03-04 | Fujisawa Pharmaceutical Co., Ltd. | Substituted 3-pyrrolidinylthio-carbapenems as antimicrobial agents |
-
1993
- 1993-03-10 CZ CZ1993393A patent/CZ290002B6/cs not_active IP Right Cessation
- 1993-03-10 FI FI931079A patent/FI103046B/fi active IP Right Grant
- 1993-03-10 HU HU9300677A patent/HU218676B/hu not_active IP Right Cessation
- 1993-03-11 CA CA002091486A patent/CA2091486A1/en not_active Abandoned
- 1993-03-11 DE DE69322188T patent/DE69322188T2/de not_active Expired - Fee Related
- 1993-03-11 RU RU9393004678A patent/RU2097383C1/ru not_active IP Right Cessation
- 1993-03-11 NZ NZ247129A patent/NZ247129A/en unknown
- 1993-03-11 IL IL105020A patent/IL105020A/xx not_active IP Right Cessation
- 1993-03-11 NO NO930884A patent/NO303730B1/no not_active IP Right Cessation
- 1993-03-11 ES ES93301872T patent/ES2125945T3/es not_active Expired - Lifetime
- 1993-03-11 KR KR1019930003664A patent/KR100258225B1/ko not_active Expired - Fee Related
- 1993-03-11 AU AU35151/93A patent/AU664422B2/en not_active Ceased
- 1993-03-11 AT AT93301872T patent/ATE173733T1/de not_active IP Right Cessation
- 1993-03-11 MX MX9301361A patent/MX9301361A/es not_active IP Right Cessation
- 1993-03-11 DK DK93301872T patent/DK0560613T3/da active
- 1993-03-11 CN CN93104412A patent/CN1037180C/zh not_active Expired - Fee Related
- 1993-03-11 TW TW082101810A patent/TW249803B/zh active
- 1993-03-11 EP EP93301872A patent/EP0560613B1/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0442497A1 (en) * | 1990-02-14 | 1991-08-21 | Sumitomo Pharmaceuticals Company, Limited | Novel beta-lactam compounds and their production |
Also Published As
| Publication number | Publication date |
|---|---|
| HU218676B (hu) | 2000-10-28 |
| FI103046B1 (fi) | 1999-04-15 |
| NO930884L (no) | 1993-09-13 |
| ATE173733T1 (de) | 1998-12-15 |
| EP0560613B1 (en) | 1998-11-25 |
| TW249803B (enExample) | 1995-06-21 |
| KR100258225B1 (ko) | 2000-08-01 |
| IL105020A (en) | 1997-04-15 |
| ES2125945T3 (es) | 1999-03-16 |
| DE69322188D1 (de) | 1999-01-07 |
| HUT64071A (en) | 1993-11-29 |
| CZ39393A3 (en) | 1993-12-15 |
| RU2097383C1 (ru) | 1997-11-27 |
| HK1011976A1 (en) | 1999-07-23 |
| CA2091486A1 (en) | 1993-09-12 |
| HU9300677D0 (en) | 1993-05-28 |
| NO303730B1 (no) | 1998-08-24 |
| NO930884D0 (no) | 1993-03-11 |
| FI931079A0 (fi) | 1993-03-10 |
| AU3515193A (en) | 1993-09-16 |
| EP0560613A1 (en) | 1993-09-15 |
| KR930019674A (ko) | 1993-10-18 |
| IL105020A0 (en) | 1993-07-08 |
| CN1079472A (zh) | 1993-12-15 |
| FI103046B (fi) | 1999-04-15 |
| DK0560613T3 (da) | 1999-08-09 |
| AU664422B2 (en) | 1995-11-16 |
| DE69322188T2 (de) | 1999-07-29 |
| NZ247129A (en) | 1994-09-27 |
| CZ290002B6 (cs) | 2002-05-15 |
| FI931079L (fi) | 1993-09-12 |
| MX9301361A (es) | 1994-01-31 |
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