IE42540B1 - Amino-substituted cephalosporins - Google Patents
Amino-substituted cephalosporinsInfo
- Publication number
- IE42540B1 IE42540B1 IE664/76A IE66476A IE42540B1 IE 42540 B1 IE42540 B1 IE 42540B1 IE 664/76 A IE664/76 A IE 664/76A IE 66476 A IE66476 A IE 66476A IE 42540 B1 IE42540 B1 IE 42540B1
- Authority
- IE
- Ireland
- Prior art keywords
- formula
- cephem
- ester
- amino
- group
- Prior art date
Links
- -1 Amino-substituted cephalosporins Chemical class 0.000 title claims abstract description 159
- 229940124587 cephalosporin Drugs 0.000 title claims description 16
- 229930186147 Cephalosporin Natural products 0.000 title claims description 13
- 150000002148 esters Chemical class 0.000 claims abstract description 12
- 150000004795 grignard reagents Chemical class 0.000 claims abstract description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 22
- 239000011541 reaction mixture Substances 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 16
- 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 claims description 15
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 14
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 239000012442 inert solvent Substances 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 239000003495 polar organic solvent Substances 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000005059 halophenyl group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 230000020477 pH reduction Effects 0.000 claims description 4
- 125000003944 tolyl group Chemical group 0.000 claims description 4
- 239000007818 Grignard reagent Substances 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 2
- 125000006501 nitrophenyl group Chemical group 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 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 2
- SQJATDDGXYUPQL-NPRFROTHSA-N benzhydryl (6r)-8-oxo-3-piperidin-1-yl-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]12)CC(N3CCCCC3)=C(C(=O)OC(C=3C=CC=CC=3)C=3C=CC=CC=3)N1C(=O)C2NC(=O)CC1=CC=CS1 SQJATDDGXYUPQL-NPRFROTHSA-N 0.000 claims 1
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 abstract description 12
- 150000003335 secondary amines Chemical class 0.000 abstract description 8
- 125000003118 aryl group Chemical group 0.000 abstract description 5
- 239000000543 intermediate Substances 0.000 abstract description 4
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 abstract description 3
- FWXJGNXYWSZXSB-SNSSHHSLSA-N benzhydryl (6r)-3-morpholin-4-yl-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]12)CC(N3CCOCC3)=C(C(=O)OC(C=3C=CC=CC=3)C=3C=CC=CC=3)N1C(=O)C2NC(=O)CC1=CC=CS1 FWXJGNXYWSZXSB-SNSSHHSLSA-N 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000000203 mixture Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 12
- 150000001408 amides Chemical class 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
- 229930192474 thiophene Natural products 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 125000004185 ester group Chemical group 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- MJSLXMHHSSCUOK-LRTDYKAYSA-N (4-nitrophenyl)methyl (6r)-3-chloro-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1=C(Cl)CS[C@H]2N1C(=O)C2NC(=O)CC1=CC=CS1 MJSLXMHHSSCUOK-LRTDYKAYSA-N 0.000 description 2
- FBZDCMZXVFLUJS-LRTDYKAYSA-N (4-nitrophenyl)methyl (6r)-3-hydroxy-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)O)C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)CC1=CC=CS1 FBZDCMZXVFLUJS-LRTDYKAYSA-N 0.000 description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 2
- QTAAZZCBEYZEMT-ZWAGFTRDSA-N benzhydryl (6r)-3-methylsulfonyloxy-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)OS(=O)(=O)C)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(=O)CC1=CC=CS1 QTAAZZCBEYZEMT-ZWAGFTRDSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000004210 ether based solvent Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- XHFGWHUWQXTGAT-UHFFFAOYSA-N n-methylpropan-2-amine Chemical compound CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000012746 preparative thin layer chromatography Methods 0.000 description 2
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- PAOJMOKNQRCLEW-VUVKHWMNSA-N (4-methoxyphenyl)methyl (6R)-3-chloro-7-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C([C@H](O)C1=CC=CC=C1)(=O)NC1[C@@H]2N(C(=C(CS2)Cl)C(=O)OCC2=CC=C(C=C2)OC)C1=O PAOJMOKNQRCLEW-VUVKHWMNSA-N 0.000 description 1
- KBRNBRSARPDLFO-ANWICMFUSA-N (4-methoxyphenyl)methyl (6r)-3-(diethylamino)-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)N(CC)CC)C(=O)OCC=1C=CC(OC)=CC=1)NC(=O)COC1=CC=CC=C1 KBRNBRSARPDLFO-ANWICMFUSA-N 0.000 description 1
- LZBBIXARISKTQV-MQNHUJCZSA-N (4-methoxyphenyl)methyl (6r)-3-butylsulfonyloxy-7-[[2-(furan-2-yl)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)OS(=O)(=O)CCCC)C(=O)OCC=1C=CC(OC)=CC=1)NC(=O)CC1=CC=CO1 LZBBIXARISKTQV-MQNHUJCZSA-N 0.000 description 1
- NSJWXAXEGOGWJE-LRTDYKAYSA-N (4-methoxyphenyl)methyl (6r)-7-amino-8-oxo-3-piperidin-1-yl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1=C(N2CCCCC2)CS[C@H]2N1C(=O)C2N NSJWXAXEGOGWJE-LRTDYKAYSA-N 0.000 description 1
- UBOWZFUCXNQUHN-ANWICMFUSA-N (4-nitrophenyl)methyl (6r)-3-(4-methylpiperazin-1-yl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1CN(C)CCN1C1=C(C(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)N2C(=O)C(NC(=O)CC=3C=CC=CC=3)[C@H]2SC1 UBOWZFUCXNQUHN-ANWICMFUSA-N 0.000 description 1
- HMHFYTVJQRFONV-GWQXNCQPSA-N (4-nitrophenyl)methyl (6r)-3-(dimethylamino)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)N(C)C)C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)CC1=CC=CC=C1 HMHFYTVJQRFONV-GWQXNCQPSA-N 0.000 description 1
- YDRINTXWMFLSTM-BDPMCISCSA-N (4-nitrophenyl)methyl (6r)-3-bromo-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1=C(Br)CS[C@H]2N1C(=O)C2NC(=O)CC1=CC=CC=C1 YDRINTXWMFLSTM-BDPMCISCSA-N 0.000 description 1
- MSJBRVIZZHKNPL-BDPMCISCSA-N (4-nitrophenyl)methyl (6r)-3-hydroxy-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)O)C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)COC1=CC=CC=C1 MSJBRVIZZHKNPL-BDPMCISCSA-N 0.000 description 1
- RODIWTUERIIATP-AVKWCDSFSA-N (4-nitrophenyl)methyl (6r)-3-methylsulfonyloxy-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)OS(=O)(=O)C)C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)COC1=CC=CC=C1 RODIWTUERIIATP-AVKWCDSFSA-N 0.000 description 1
- YGUADQMOZUNHBJ-UUSAFJCLSA-N (4-nitrophenyl)methyl (6r)-3-methylsulfonyloxy-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)OS(=O)(=O)C)C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)CC1=CC=CS1 YGUADQMOZUNHBJ-UUSAFJCLSA-N 0.000 description 1
- DCZBJZDUJLPFLD-NRWPOFLRSA-N (4-nitrophenyl)methyl (6r)-3-morpholin-4-yl-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1=C(N2CCOCC2)CS[C@H]2N1C(=O)C2NC(=O)COC1=CC=CC=C1 DCZBJZDUJLPFLD-NRWPOFLRSA-N 0.000 description 1
- NKOWXFPEYXERPE-NRWPOFLRSA-N (4-nitrophenyl)methyl (6r)-3-morpholin-4-yl-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1=C(N2CCOCC2)CS[C@H]2N1C(=O)C2NC(=O)CC1=CC=CC=C1 NKOWXFPEYXERPE-NRWPOFLRSA-N 0.000 description 1
- URHKFYORDUYVQG-FQNRMIAFSA-N (4-nitrophenyl)methyl (6r)-7-acetamido-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N11)=O)NC(=O)C)CC(C)=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 URHKFYORDUYVQG-FQNRMIAFSA-N 0.000 description 1
- WTLFNHOYDNKXES-FQNRMIAFSA-N (4-nitrophenyl)methyl (6r)-7-acetamido-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N11)=O)NC(=O)C)CC(OS(C)(=O)=O)=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 WTLFNHOYDNKXES-FQNRMIAFSA-N 0.000 description 1
- JQTJHBULIZANSY-FBMWCMRBSA-N (4-nitrophenyl)methyl (6r)-7-amino-8-oxo-3-thiomorpholin-4-yl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N1C=1C(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)=O)N)CC=1N1CCSCC1 JQTJHBULIZANSY-FBMWCMRBSA-N 0.000 description 1
- XIOOBRKSYSUFNC-LFHRXCRSSA-N (4-nitrophenyl)methyl (6r)-8-oxo-3-phenyl-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1=C(C=2C=CC=CC=2)CS[C@H]2N1C(=O)C2NC(=O)CC1=CC=CC=C1 XIOOBRKSYSUFNC-LFHRXCRSSA-N 0.000 description 1
- AWDGVJXGDQEGKU-ANWICMFUSA-N (4-nitrophenyl)methyl (6r)-8-oxo-7-[(2-phenoxyacetyl)amino]-3-piperidin-1-yl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1=C(N2CCCCC2)CS[C@H]2N1C(=O)C2NC(=O)COC1=CC=CC=C1 AWDGVJXGDQEGKU-ANWICMFUSA-N 0.000 description 1
- YLIOIMWNSIRKDG-ZWNOBZJWSA-N (4-nitrophenyl)methyl (6r,7r)-7-amino-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1[C@@H](C(N11)=O)N)CC(Cl)=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 YLIOIMWNSIRKDG-ZWNOBZJWSA-N 0.000 description 1
- UKXNBTWFZIILJZ-GFCCVEGCSA-N (6R)-3-phenyl-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class C1(=CC=CC=C1)C=1CS[C@H]2N(C=1)C(C2)=O UKXNBTWFZIILJZ-GFCCVEGCSA-N 0.000 description 1
- PRNKRNJGWFYPAO-QVDQXJPCSA-N (6R)-4-(diethylamino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CCN(CC)C1C=C(N2[C@H](S1)CC2=O)C(=O)O PRNKRNJGWFYPAO-QVDQXJPCSA-N 0.000 description 1
- AYTHYBVDCYEPLD-SBXXRYSUSA-N (6r)-3-ethyl-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)CC)C(O)=O)NC(=O)CC1=CC=CS1 AYTHYBVDCYEPLD-SBXXRYSUSA-N 0.000 description 1
- ZUBXPSDFPQTKQN-ZCFIWIBFSA-N (6r)-3-hydroxy-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC(O)=CN2C(=O)C[C@H]21 ZUBXPSDFPQTKQN-ZCFIWIBFSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- YKSVXVKIYYQWBB-UHFFFAOYSA-N 1-butylpiperazine Chemical compound CCCCN1CCNCC1 YKSVXVKIYYQWBB-UHFFFAOYSA-N 0.000 description 1
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- KJVJSJCHFATJDU-WPZCJLIBSA-N 2,2,2-trichloroethyl (6r)-3-chloro-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)Cl)C(=O)OCC(Cl)(Cl)Cl)NC(=O)COC1=CC=CC=C1 KJVJSJCHFATJDU-WPZCJLIBSA-N 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- NWWJFMCCTZLKNT-UHFFFAOYSA-N 3,4-dihydro-2h-thiazine Chemical group C1CC=CSN1 NWWJFMCCTZLKNT-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- TZMWKLJHNXQJQW-ULUSZKPHSA-N [(6R)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-4-yl] methanesulfonate Chemical class CS(=O)(=O)OC1S[C@H]2N(C=C1)C(C2)=O TZMWKLJHNXQJQW-ULUSZKPHSA-N 0.000 description 1
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 125000000746 allylic group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- SWOAMZJZPDIMLM-FKCQOYNMSA-N benzhydryl (6R)-7-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C([C@H](O)C1=CC=CC=C1)(=O)NC1[C@@H]2N(C(=C(CS2)OS(=O)(=O)C)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O SWOAMZJZPDIMLM-FKCQOYNMSA-N 0.000 description 1
- XIGAKXQFFLCWFE-YSPRKPHLSA-N benzhydryl (6R)-7-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-3-morpholin-4-yl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C([C@H](O)C1=CC=CC=C1)(=O)NC1[C@@H]2N(C(=C(CS2)N2CCOCC2)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O XIGAKXQFFLCWFE-YSPRKPHLSA-N 0.000 description 1
- HKJPIBFJHUNQRU-VCHQGTEKSA-N benzhydryl (6r)-3-(4-methylphenyl)sulfonyloxy-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1=C(C(=O)OC(C=2C=CC=CC=2)C=2C=CC=CC=2)N2C(=O)C(NC(=O)CC=3SC=CC=3)[C@H]2SC1 HKJPIBFJHUNQRU-VCHQGTEKSA-N 0.000 description 1
- UMNSDNIEDPVJEL-IQHZPMLTSA-N benzhydryl (6r)-3-bromo-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)Br)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(=O)CC1=CC=CC=C1 UMNSDNIEDPVJEL-IQHZPMLTSA-N 0.000 description 1
- GCNRPGPJAHPWOY-IQHZPMLTSA-N benzhydryl (6r)-3-ethyl-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)CC)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(=O)CC1=CC=CS1 GCNRPGPJAHPWOY-IQHZPMLTSA-N 0.000 description 1
- HQQAEHBMMRUMGD-FBLFFUNLSA-N benzhydryl (6r)-7-acetamido-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N11)=O)NC(=O)C)CC(Cl)=C1C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 HQQAEHBMMRUMGD-FBLFFUNLSA-N 0.000 description 1
- MOXQGYJZWQYUNK-SNSSHHSLSA-N benzhydryl (6r)-8-oxo-3-pyrrolidin-1-yl-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]12)CC(N3CCCC3)=C(C(=O)OC(C=3C=CC=CC=3)C=3C=CC=CC=3)N1C(=O)C2NC(=O)CC1=CC=CS1 MOXQGYJZWQYUNK-SNSSHHSLSA-N 0.000 description 1
- GCJFISTXDGUTGB-MMZZDGEESA-N benzyl (6R)-7-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-8-oxo-3-piperidin-1-yl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C([C@H](O)C1=CC=CC=C1)(=O)NC1[C@@H]2N(C(=C(CS2)N2CCCCC2)C(=O)OCC2=CC=CC=C2)C1=O GCJFISTXDGUTGB-MMZZDGEESA-N 0.000 description 1
- ZTIMYJKYTRFILT-AVKWCDSFSA-N benzyl (6r)-3-methylsulfonyloxy-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)OS(=O)(=O)C)C(=O)OCC=1C=CC=CC=1)NC(=O)COC1=CC=CC=C1 ZTIMYJKYTRFILT-AVKWCDSFSA-N 0.000 description 1
- JURVIJCQWUXDMZ-AVKWCDSFSA-N benzyl (6r)-8-oxo-7-[[2-(1,3-thiazol-2-yl)acetyl]amino]-3-thiomorpholin-4-yl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]12)CC(N3CCSCC3)=C(C(=O)OCC=3C=CC=CC=3)N1C(=O)C2NC(=O)CC1=NC=CS1 JURVIJCQWUXDMZ-AVKWCDSFSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001782 cephems Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 150000005218 dimethyl ethers Chemical class 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000004970 halomethyl group Chemical group 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- LWLPYZUDBNFNAH-UHFFFAOYSA-M magnesium;butane;bromide Chemical compound [Mg+2].[Br-].CCC[CH2-] LWLPYZUDBNFNAH-UHFFFAOYSA-M 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
- UGVPKMAWLOMPRS-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].CC[CH2-] UGVPKMAWLOMPRS-UHFFFAOYSA-M 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- WOHOHPONCSKXSQ-UHFFFAOYSA-N n-ethyl-2-phenylethanamine Chemical compound CCNCCC1=CC=CC=C1 WOHOHPONCSKXSQ-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- CWYZDPHNAGSFQB-UHFFFAOYSA-N n-propylbutan-1-amine Chemical compound CCCCNCCC CWYZDPHNAGSFQB-UHFFFAOYSA-N 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- WURFKUQACINBSI-UHFFFAOYSA-M ozonide Chemical compound [O]O[O-] WURFKUQACINBSI-UHFFFAOYSA-M 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- NUDLMFKZXZADGG-UUSAFJCLSA-N phenacyl (6r)-7-acetamido-3-morpholin-4-yl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N1C=1C(=O)OCC(=O)C=2C=CC=CC=2)=O)NC(=O)C)CC=1N1CCOCC1 NUDLMFKZXZADGG-UUSAFJCLSA-N 0.000 description 1
- RTJJYMDUVLOSPR-FBLFFUNLSA-N phenacyl (6r)-7-benzamido-3-bromo-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)Br)C(=O)OCC(=O)C=1C=CC=CC=1)NC(=O)C1=CC=CC=C1 RTJJYMDUVLOSPR-FBLFFUNLSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 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
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/04—Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/59—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3 with hetero atoms directly attached in position 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/576,818 US4013651A (en) | 1975-05-12 | 1975-05-12 | 3-substituted amino-cephalosporins |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE42540L IE42540L (en) | 1976-11-12 |
| IE42540B1 true IE42540B1 (en) | 1980-08-27 |
Family
ID=24306128
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE664/76A IE42540B1 (en) | 1975-05-12 | 1976-03-30 | Amino-substituted cephalosporins |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US4013651A (en, 2012) |
| JP (1) | JPS51138697A (en, 2012) |
| BE (1) | BE841496A (en, 2012) |
| CA (1) | CA1074782A (en, 2012) |
| CH (3) | CH623054A5 (en, 2012) |
| DE (1) | DE2620308A1 (en, 2012) |
| ES (3) | ES447806A1 (en, 2012) |
| GB (1) | GB1544984A (en, 2012) |
| IE (1) | IE42540B1 (en, 2012) |
| IL (1) | IL49318A (en, 2012) |
| NL (3) | NL7605075A (en, 2012) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3947413A (en) * | 1972-11-13 | 1976-03-30 | Merck & Co., Inc. | 3-α-Substituted cephalosporins |
| AT342197B (de) * | 1975-02-20 | 1978-03-28 | Ciba Geigy Ag | Neues verfahren zur herstellung von 3-cephemverbindungen |
| US4434287A (en) | 1975-02-20 | 1984-02-28 | Ciba-Geigy Corporation | Cephalosporin derivatives |
| US4550162A (en) * | 1975-02-20 | 1985-10-29 | Ciba-Geigy Corporation | Process for the manufacture of enol derivatives |
| JPS543087A (en) * | 1977-06-03 | 1979-01-11 | Fujisawa Pharmaceut Co Ltd | Preparation of cephalosporin compound |
| US4244885A (en) * | 1977-12-08 | 1981-01-13 | Yeda Research And Development Co. Ltd. | α-Substituted-3-(halomethyl)-4-hydroxybenzeneacetic acids |
| US4436903A (en) | 1980-12-22 | 1984-03-13 | Ciba-Geigy Corporation | Process for the production of 7 β-substituted-3-unsubstituted-3-cephem-4-carboxylic acid compounds |
| US4533497A (en) * | 1982-12-27 | 1985-08-06 | Eli Lilly And Company | N-ethylidene azetidinones |
| US5019571A (en) * | 1988-01-25 | 1991-05-28 | Eli Lilly And Company | 1-carbacephalosporin antibiotics |
| ES2055030T3 (es) * | 1988-01-25 | 1994-08-16 | Lilly Co Eli | Antibioticos de 1-carbacefalosporina. |
| WO2017190043A1 (en) * | 2016-04-29 | 2017-11-02 | University Of Kansas | Cephalosporin-type compounds |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE412238B (sv) * | 1971-05-24 | 1980-02-25 | Ciba Geigy | Forfarande for framstellning av 7 beta-amino-cefem-4-karboxylsyraforeningar genom dekarbonylering av en 3-formyl-cefem-4-karboxylsyraforening |
| US4001226A (en) * | 1974-12-04 | 1977-01-04 | Eli Lilly And Company | 3-(substituted)carbonylamino cephem derivatives |
| JPS609516B2 (ja) * | 1975-03-07 | 1985-03-11 | 塩野義製薬株式会社 | セフエム骨格の環化製法 |
| AT342197B (de) * | 1975-02-20 | 1978-03-28 | Ciba Geigy Ag | Neues verfahren zur herstellung von 3-cephemverbindungen |
-
1975
- 1975-05-12 US US05/576,818 patent/US4013651A/en not_active Expired - Lifetime
-
1976
- 1976-03-30 IE IE664/76A patent/IE42540B1/en unknown
- 1976-03-31 IL IL49318A patent/IL49318A/xx unknown
- 1976-04-01 CA CA249,339A patent/CA1074782A/en not_active Expired
- 1976-05-05 GB GB18312/76A patent/GB1544984A/en not_active Expired
- 1976-05-06 BE BE1007359A patent/BE841496A/xx not_active IP Right Cessation
- 1976-05-07 DE DE19762620308 patent/DE2620308A1/de not_active Withdrawn
- 1976-05-11 ES ES447806A patent/ES447806A1/es not_active Expired
- 1976-05-11 ES ES447807A patent/ES447807A1/es not_active Expired
- 1976-05-11 JP JP51054245A patent/JPS51138697A/ja active Pending
- 1976-05-11 ES ES447805A patent/ES447805A1/es not_active Expired
- 1976-05-12 CH CH595376A patent/CH623054A5/de not_active IP Right Cessation
- 1976-05-12 CH CH595476A patent/CH621123A5/de not_active IP Right Cessation
- 1976-05-12 NL NL7605075A patent/NL7605075A/xx not_active Application Discontinuation
- 1976-05-12 NL NL7605078A patent/NL7605078A/xx not_active Application Discontinuation
- 1976-05-12 NL NL7605077A patent/NL7605077A/xx not_active Application Discontinuation
- 1976-05-12 CH CH595576A patent/CH619958A5/de not_active IP Right Cessation
- 1976-09-03 US US05/720,180 patent/US4065621A/en not_active Expired - Lifetime
- 1976-09-03 US US05/720,179 patent/US4065618A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| NL7605078A (nl) | 1976-11-16 |
| CA1074782A (en) | 1980-04-01 |
| IE42540L (en) | 1976-11-12 |
| US4065618A (en) | 1977-12-27 |
| IL49318A (en) | 1980-03-31 |
| CH619958A5 (en, 2012) | 1980-10-31 |
| NL7605077A (nl) | 1976-11-16 |
| ES447807A1 (es) | 1977-10-01 |
| US4065621A (en) | 1977-12-27 |
| ES447805A1 (es) | 1978-04-01 |
| GB1544984A (en) | 1979-04-25 |
| CH621123A5 (en, 2012) | 1981-01-15 |
| IL49318A0 (en) | 1976-05-31 |
| NL7605075A (nl) | 1976-11-16 |
| US4013651A (en) | 1977-03-22 |
| ES447806A1 (es) | 1977-10-01 |
| BE841496A (fr) | 1976-11-08 |
| JPS51138697A (en) | 1976-11-30 |
| DE2620308A1 (de) | 1976-11-25 |
| CH623054A5 (en, 2012) | 1981-05-15 |
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