CA1064019A - Cepham derivatives and preparation thereof - Google Patents
Cepham derivatives and preparation thereofInfo
- Publication number
- CA1064019A CA1064019A CA211,504A CA211504A CA1064019A CA 1064019 A CA1064019 A CA 1064019A CA 211504 A CA211504 A CA 211504A CA 1064019 A CA1064019 A CA 1064019A
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- group
- cephem
- hydrogen
- tetrazol
- 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
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 150000001781 cephams Chemical class 0.000 title description 3
- FZEVMBJWXHDLDB-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC=CN2C(=O)C[C@H]21 FZEVMBJWXHDLDB-ZCFIWIBFSA-N 0.000 claims abstract description 84
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims description 150
- -1 2,2,2-trichloroethoxycarbonyl Chemical group 0.000 claims description 149
- 150000001875 compounds Chemical class 0.000 claims description 90
- 230000008569 process Effects 0.000 claims description 86
- 239000001257 hydrogen Substances 0.000 claims description 78
- 229910052739 hydrogen Inorganic materials 0.000 claims description 78
- 125000004432 carbon atom Chemical group C* 0.000 claims description 72
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 35
- SXBDXXFTJVHSAF-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-3-en-8-one Chemical compound S1C=CCN2C(=O)C[C@H]21 SXBDXXFTJVHSAF-ZCFIWIBFSA-N 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 27
- 239000007858 starting material Substances 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 21
- 150000001782 cephems Chemical class 0.000 claims description 19
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 19
- 125000004423 acyloxy group Chemical group 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 125000001246 bromo group Chemical group Br* 0.000 claims description 17
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 16
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
- 125000005633 phthalidyl group Chemical group 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 230000015572 biosynthetic process Effects 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- 238000005917 acylation reaction Methods 0.000 claims description 10
- 150000001540 azides Chemical class 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 230000010933 acylation Effects 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 229910052717 sulfur Chemical group 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 230000029936 alkylation Effects 0.000 claims description 8
- 238000005804 alkylation reaction Methods 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 8
- 239000011593 sulfur Chemical group 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 239000002243 precursor Substances 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 230000002152 alkylating effect Effects 0.000 claims description 4
- 150000008064 anhydrides Chemical group 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000005030 pyridylthio group Chemical group N1=C(C=CC=C1)S* 0.000 claims description 4
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 3
- 125000002188 cycloheptatrienyl group Chemical group C1(=CC=CC=CC1)* 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 230000002140 halogenating effect Effects 0.000 claims description 3
- WSHJJCPTKWSMRR-RXMQYKEDSA-N penam Chemical compound S1CCN2C(=O)C[C@H]21 WSHJJCPTKWSMRR-RXMQYKEDSA-N 0.000 claims description 3
- 230000036647 reaction Effects 0.000 claims description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 2
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical group C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 27
- 125000005846 1-(alkanoyloxy)ethyl group Chemical group 0.000 claims 9
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 6
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 claims 4
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 claims 2
- SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical compound OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-N 0.000 claims 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims 2
- 159000000021 acetate salts Chemical class 0.000 claims 2
- 150000001263 acyl chlorides Chemical class 0.000 claims 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 2
- 241000011102 Thera Species 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 17
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 10
- 239000000243 solution Substances 0.000 description 111
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 68
- 238000005481 NMR spectroscopy Methods 0.000 description 65
- 239000000203 mixture Substances 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- 239000000047 product Substances 0.000 description 50
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
- 239000007787 solid Substances 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 239000002253 acid Substances 0.000 description 36
- 229940093499 ethyl acetate Drugs 0.000 description 34
- 235000019439 ethyl acetate Nutrition 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 21
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 20
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 19
- 150000003536 tetrazoles Chemical class 0.000 description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
- 239000002244 precipitate Substances 0.000 description 18
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 16
- 229940022682 acetone Drugs 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- 235000011167 hydrochloric acid Nutrition 0.000 description 13
- 229960000443 hydrochloric acid Drugs 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 239000003208 petroleum Substances 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229960001407 sodium bicarbonate Drugs 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 238000007792 addition Methods 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 230000008020 evaporation Effects 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 235000011054 acetic acid Nutrition 0.000 description 8
- 239000003242 anti bacterial agent Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 8
- 239000000039 congener Substances 0.000 description 7
- 230000000875 corresponding effect Effects 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 229940086542 triethylamine Drugs 0.000 description 7
- 238000001665 trituration Methods 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 6
- 159000000000 sodium salts Chemical class 0.000 description 6
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 5
- QHTOIDKCEPKVCM-ZCFIWIBFSA-N cepham Chemical compound S1CCCN2C(=O)C[C@H]21 QHTOIDKCEPKVCM-ZCFIWIBFSA-N 0.000 description 5
- JSYGRUBHOCKMGQ-UHFFFAOYSA-N dichloramine Chemical compound ClNCl JSYGRUBHOCKMGQ-UHFFFAOYSA-N 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 4
- 125000003713 acetylimino group Chemical group [H]C([H])([H])C(=O)N=[*] 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 150000001447 alkali salts Chemical class 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 229960004132 diethyl ether Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 230000000873 masking effect Effects 0.000 description 4
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- IKWLIQXIPRUIDU-ZCFIWIBFSA-N (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CCS[C@@H]2CC(=O)N12 IKWLIQXIPRUIDU-ZCFIWIBFSA-N 0.000 description 3
- ZMMRLWFGWQVVJD-UHFFFAOYSA-O (n,n-dimethylcarbamimidoyl)-dimethylazanium;azide Chemical compound [N-]=[N+]=[N-].CN(C)C(N)=[N+](C)C ZMMRLWFGWQVVJD-UHFFFAOYSA-O 0.000 description 3
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 229940022663 acetate Drugs 0.000 description 3
- 230000031709 bromination Effects 0.000 description 3
- 238000005893 bromination reaction Methods 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229960005419 nitrogen Drugs 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229940093932 potassium hydroxide Drugs 0.000 description 3
- 235000011118 potassium hydroxide Nutrition 0.000 description 3
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 3
- 230000002633 protecting effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
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- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 235000021384 green leafy vegetables Nutrition 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000015250 liver sausages Nutrition 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 1
- 235000007708 morin Nutrition 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- IOQPZZOEVPZRBK-UHFFFAOYSA-N octan-1-amine Chemical compound CCCCCCCCN IOQPZZOEVPZRBK-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 235000007686 potassium Nutrition 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- UYCAUPASBSROMS-AWQJXPNKSA-M sodium;2,2,2-trifluoroacetate Chemical compound [Na+].[O-][13C](=O)[13C](F)(F)F UYCAUPASBSROMS-AWQJXPNKSA-M 0.000 description 1
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 229940013123 stannous chloride Drugs 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000002311 subsequent effect Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- 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)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40709773A | 1973-10-17 | 1973-10-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1064019A true CA1064019A (en) | 1979-10-09 |
Family
ID=23610572
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA211,504A Expired CA1064019A (en) | 1973-10-17 | 1974-10-16 | Cepham derivatives and preparation thereof |
Country Status (22)
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2833121A1 (en) * | 2011-04-28 | 2012-11-01 | Shionogi & Co., Ltd. | Novel cephem compound having catechol or pseudo-catechol structure |
| WO2013002215A1 (ja) * | 2011-06-27 | 2013-01-03 | 塩野義製薬株式会社 | ピリジニウム基を有するセフェム化合物 |
-
1974
- 1974-10-07 SE SE7412602A patent/SE429342B/xx unknown
- 1974-10-11 NO NO743667A patent/NO743667L/no unknown
- 1974-10-14 GB GB22873/76A patent/GB1481810A/en not_active Expired
- 1974-10-14 GB GB22871/76A patent/GB1481808A/en not_active Expired
- 1974-10-14 IL IL45849A patent/IL45849A0/xx unknown
- 1974-10-14 IE IE2113/74A patent/IE40745B1/xx unknown
- 1974-10-14 GB GB22872/76A patent/GB1481809A/en not_active Expired
- 1974-10-14 GB GB44350/74A patent/GB1481807A/en not_active Expired
- 1974-10-15 ZA ZA00746544A patent/ZA746544B/xx unknown
- 1974-10-15 MW MW40/74A patent/MW4074A1/xx unknown
- 1974-10-15 MW MW41/74A patent/MW4174A1/xx unknown
- 1974-10-16 DK DK542174A patent/DK542174A/da not_active Application Discontinuation
- 1974-10-16 CA CA211,504A patent/CA1064019A/en not_active Expired
- 1974-10-16 ES ES431069A patent/ES431069A1/es not_active Expired
- 1974-10-16 AR AR256116A patent/AR209283A1/es active
- 1974-10-16 DD DD181737A patent/DD114266A5/xx unknown
- 1974-10-16 DE DE19742449834 patent/DE2449834A1/de not_active Ceased
- 1974-10-17 NL NL7413643A patent/NL7413643A/xx not_active Application Discontinuation
- 1974-10-17 FR FR7435015A patent/FR2257298B1/fr not_active Expired
- 1974-10-17 BE BE1006235A patent/BE821164A/xx unknown
- 1974-10-17 LU LU71128A patent/LU71128A1/xx unknown
- 1974-10-17 JP JP49118743A patent/JPS50121293A/ja active Pending
- 1974-10-17 PL PL1974174893A patent/PL95747B1/pl unknown
- 1974-10-18 OA OA55326A patent/OA04935A/xx unknown
- 1974-11-04 ZM ZM161/74A patent/ZM16174A1/xx unknown
-
1975
- 1975-08-18 AR AR260031A patent/AR213726A1/es active
-
1976
- 1976-08-02 ES ES450398A patent/ES450398A1/es not_active Expired
- 1976-08-02 ES ES450397A patent/ES450397A1/es not_active Expired
- 1976-08-02 ES ES450399A patent/ES450399A1/es not_active Expired
-
1977
- 1977-09-23 SE SE7710697A patent/SE7710697L/xx not_active Application Discontinuation
-
1978
- 1978-06-28 SU SU782377452A patent/SU974936A3/ru active
-
1982
- 1982-01-20 JP JP57007361A patent/JPS5822480B2/ja not_active Expired
-
1983
- 1983-01-17 JP JP58005766A patent/JPS58131988A/ja active Pending
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