CH619958A5 - - Google Patents

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Publication number: CH619958A5
Authority: CH; Switzerland
Prior art keywords: formula; amino; substituent; cephem; thienyl
Prior art date: 1975-05-12

Application number

CH595576A

Other languages

German (de)

English (en)

Inventor

Wayne Alfred Spitzer

Original Assignee

Lilly Co Eli

Priority date (The priority date 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 date listed.)

1975-05-12

Filing date

1976-05-12

Publication date

1980-10-31

1976-05-12 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

1980-10-31 Publication of CH619958A5 publication Critical patent/CH619958A5/de

Links

-1 pyrrolidino, piperidino, morpholino, thiomorpholino Chemical group 0.000 claims description 123
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
125000001424 substituent group Chemical group 0.000 claims description 20
239000011541 reaction mixture Substances 0.000 claims description 17
238000000034 method Methods 0.000 claims description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 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 claims description 6
125000004185 ester group Chemical group 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
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 6
125000001544 thienyl group Chemical group 0.000 claims description 6
239000012442 inert 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
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
125000005059 halophenyl group Chemical group 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
239000011593 sulfur Substances 0.000 claims description 4
125000003944 tolyl group Chemical group 0.000 claims description 4
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 3
229910052757 nitrogen Inorganic materials 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 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
229910006069 SO3H Inorganic materials 0.000 claims 3
125000004464 hydroxyphenyl group Chemical group 0.000 claims 3
125000006501 nitrophenyl group Chemical group 0.000 claims 3
125000002541 furyl group Chemical group 0.000 claims 2
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 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
239000000243 solution Substances 0.000 description 20
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
239000000047 product Substances 0.000 description 8
239000012267 brine Substances 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
239000000203 mixture Substances 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 5
239000002253 acid Substances 0.000 description 5
125000000217 alkyl group Chemical group 0.000 description 5
150000003335 secondary amines Chemical class 0.000 description 5
229930192474 thiophene Natural products 0.000 description 5
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-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
238000005481 NMR spectroscopy Methods 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
239000012043 crude product Substances 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000003756 stirring Methods 0.000 description 4
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 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000002904 solvent Substances 0.000 description 3
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
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
238000000862 absorption spectrum Methods 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
229940088710 antibiotic agent Drugs 0.000 description 2
125000005279 aryl sulfonyloxy group Chemical group 0.000 description 2
150000001875 compounds Chemical class 0.000 description 2
JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 2
239000004210 ether based solvent Substances 0.000 description 2
229910052740 iodine Inorganic materials 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
238000004519 manufacturing process Methods 0.000 description 2
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-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
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
239000003495 polar organic solvent Substances 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
239000007858 starting material Substances 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
BJYNEWYPMMYDKH-BDPMCISCSA-N (4-nitrophenyl)methyl (6r)-3-chloro-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(Cl)CS[C@H]2N1C(=O)C2NC(=O)COC1=CC=CC=C1 BJYNEWYPMMYDKH-BDPMCISCSA-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
LFUQFKPSWZXXTJ-SCPLRKQGSA-N (6R)-3-butylsulfonyloxy-7-[[2-(furan-2-yl)acetyl]amino]-4-[(4-methoxyphenyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CCCCS(=O)(=O)OC1=C(N2[C@@H](C(C2=O)NC(=O)CC3=CC=CO3)SC1CC4=CC=C(C=C4)OC)C(=O)O LFUQFKPSWZXXTJ-SCPLRKQGSA-N 0.000 description 1
POOKJCRWTVIDAI-YKEBJSDKSA-N (6R)-3-chloro-7-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-4-[(4-methoxyphenyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound COC1=CC=C(C=C1)CC2C(=C(N3[C@H](S2)C(C3=O)NC(=O)[C@@H](C4=CC=CC=C4)O)C(=O)O)Cl POOKJCRWTVIDAI-YKEBJSDKSA-N 0.000 description 1
VHDAYWYWLBGZAY-QJXPYNDKSA-N (6R)-3-methylsulfonyloxy-4-[(4-nitrophenyl)methyl]-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CS(=O)(=O)OC1=C(N2[C@@H](C(C2=O)NC(=O)CC3=CC=CS3)SC1CC4=CC=C(C=C4)[N+](=O)[O-])C(=O)O VHDAYWYWLBGZAY-QJXPYNDKSA-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
WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
229930186147 Cephalosporin Natural products 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
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
239000000010 aprotic solvent Substances 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
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 1
ZHMXHYGLHUGWTL-SLJLDQLWSA-N benzhydryl (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 S([C@@H]12)CC(N3CCOCC3)=C(C(=O)OC(C=3C=CC=CC=3)C=3C=CC=CC=3)N1C(=O)C2NC(=O)COC1=CC=CC=C1 ZHMXHYGLHUGWTL-SLJLDQLWSA-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
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 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
230000003115 biocidal effect Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
150000001733 carboxylic acid esters Chemical class 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
229940124587 cephalosporin Drugs 0.000 description 1
150000001780 cephalosporins Chemical class 0.000 description 1
125000001550 cephem group Chemical group 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 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
WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
238000010828 elution Methods 0.000 description 1
LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
239000011630 iodine Substances 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
239000000463 material Substances 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
238000004452 microanalysis Methods 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
QHCCDDQKNUYGNC-UHFFFAOYSA-N n-ethylbutan-1-amine Chemical compound CCCCNCC QHCCDDQKNUYGNC-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
XHFGWHUWQXTGAT-UHFFFAOYSA-N n-methylpropan-2-amine Chemical compound CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
231100000989 no adverse effect Toxicity 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
SNKCPKNSZBDZII-IQHZPMLTSA-N phenacyl (6r)-7-benzamido-3-(benzenesulfonyloxy)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@H]2SCC(=C(N2C1=O)C(=O)OCC(=O)C=1C=CC=CC=1)OS(=O)(=O)C=1C=CC=CC=1)NC(=O)C1=CC=CC=C1 SNKCPKNSZBDZII-IQHZPMLTSA-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
229920000728 polyester Polymers 0.000 description 1
238000012746 preparative thin layer chromatography Methods 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
230000008707 rearrangement Effects 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
238000010898 silica gel chromatography Methods 0.000 description 1
WFGZXJZWWJWJCF-ALLBUHFWSA-N tert-butyl (6r)-3-chloro-7-[[3-[(2-methylpropan-2-yl)oxy]-3-oxo-2-phenylpropanoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]12)CC(Cl)=C(C(=O)OC(C)(C)C)N1C(=O)C2NC(=O)C(C(=O)OC(C)(C)C)C1=CC=CC=C1 WFGZXJZWWJWJCF-ALLBUHFWSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
150000003952 β-lactams Chemical class 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)

CH595576A 1975-05-12 1976-05-12 CH619958A5 (fr)

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 (1)

Publication Number	Publication Date
CH619958A5 true CH619958A5 (fr)	1980-10-31

Family

ID=24306128

Family Applications (3)

Application Number	Title	Priority Date
CH595376A CH623054A5 (fr)	1975-05-12	1976-05-12
CH595476A CH621123A5 (fr)	1975-05-12	1976-05-12
CH595576A CH619958A5 (fr)	1975-05-12	1976-05-12

Family Applications Before (2)

Application Number	Title	Priority Date	Filing Date
CH595376A CH623054A5 (fr)	1975-05-12	1976-05-12
CH595476A CH621123A5 (fr)	1975-05-12	1976-05-12

Country Status (11)

Country	Link
US (3)	US4013651A (fr)
JP (1)	JPS51138697A (fr)
BE (1)	BE841496A (fr)
CA (1)	CA1074782A (fr)
CH (3)	CH623054A5 (fr)
DE (1)	DE2620308A1 (fr)
ES (3)	ES447805A1 (fr)
GB (1)	GB1544984A (fr)
IE (1)	IE42540B1 (fr)
IL (1)	IL49318A (fr)
NL (3)	NL7605077A (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3947413A (en) *	1972-11-13	1976-03-30	Merck & Co., Inc.	3-α-Substituted cephalosporins
US4550162A (en) *	1975-02-20	1985-10-29	Ciba-Geigy Corporation	Process for the manufacture of enol derivatives
AT342197B (de) *	1975-02-20	1978-03-28	Ciba Geigy Ag	Neues verfahren zur herstellung von 3-cephemverbindungen
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
DE68916275T2 (de) *	1988-01-25	1994-11-17	Lilly Co Eli	1-Carbacephalosporin-Antibiotika.
WO2017190043A1 (fr) *	2016-04-29	2017-11-02	University Of Kansas	Composés de type céphalosporine

Family Cites Families (4)

* Cited by examiner, † Cited by third party
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/fr not_active Expired
- 1976-05-05 GB GB18312/76A patent/GB1544984A/en not_active Expired
- 1976-05-06 BE BE1007359A patent/BE841496A/fr not_active IP Right Cessation
- 1976-05-07 DE DE19762620308 patent/DE2620308A1/de not_active Withdrawn
- 1976-05-11 ES ES447805A patent/ES447805A1/es not_active Expired
- 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
- 1976-05-12 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 CH CH595576A patent/CH619958A5/de not_active IP Right Cessation
- 1976-05-12 NL NL7605077A patent/NL7605077A/xx not_active Application Discontinuation
- 1976-05-12 NL NL7605078A patent/NL7605078A/xx not_active Application Discontinuation
- 1976-05-12 NL NL7605075A patent/NL7605075A/xx not_active Application Discontinuation
- 1976-09-03 US US05/720,179 patent/US4065618A/en not_active Expired - Lifetime
- 1976-09-03 US US05/720,180 patent/US4065621A/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
NL7605077A (nl)	1976-11-16
IL49318A (en)	1980-03-31
BE841496A (fr)	1976-11-08
CH623054A5 (fr)	1981-05-15
NL7605075A (nl)	1976-11-16
ES447805A1 (es)	1978-04-01
CH621123A5 (fr)	1981-01-15
US4065618A (en)	1977-12-27
IL49318A0 (en)	1976-05-31
IE42540B1 (en)	1980-08-27
NL7605078A (nl)	1976-11-16
JPS51138697A (en)	1976-11-30
CA1074782A (fr)	1980-04-01
ES447806A1 (es)	1977-10-01
GB1544984A (en)	1979-04-25
US4013651A (en)	1977-03-22
ES447807A1 (es)	1977-10-01
DE2620308A1 (de)	1976-11-25
US4065621A (en)	1977-12-27
IE42540L (en)	1976-11-12

Publication	Publication Date	Title
DE2555858A1 (de)	1976-06-16	3-thiosubstituierte cephalosporinverbindungen und verfahren zu ihrer herstellung
CH615436A5 (en)	1980-01-31	Process for the preparation of the syn-isomer or of a mixture of syn- and anti-isomers of novel 7-alpha-substituted 7-beta-acylaminoceph-3-em-4-carboxylic acids
EP0789019B1 (fr)	2001-06-13	Procédé pour la préparation de sels du 4-oxoimidazolinium
DE2606196C2 (fr)	1990-07-26
CH619958A5 (fr)	1980-10-31
DE2304226B2 (de)	1979-07-19	Verfahren zur Herstellung von Penicillinen und Cephalosporinen
CH662120A5 (de)	1987-09-15	Verfahren zur herstellung von cephalosporinen.
EP2435441A1 (fr)	2012-04-04	Procédé de préparation de ceftobiprole médocaril
DE2431484C2 (de)	1982-10-21	Verfahren zur Herstellung von 7 beta- Amino-7 alpha-methoxy-3-cephemestern
DE3216256C2 (fr)	1989-12-21
CH616683A5 (en)	1980-04-15	Process for the preparation of cephalosporins
DE2451931C2 (de)	1985-08-01	7&beta;-Acylamido-7&alpha;-methoxycephalosporine, Verfahren zu ihrer Herstellung und sie enthaltendes antibiotisches Mittel
DE2417988A1 (de)	1975-08-07	Verfahren zur herstellung von 7-acylamido-3-fluor-3-cephem-4-carbonsaeureestern und -saeuren
CH642968A5 (de)	1984-05-15	Cephalosporin-analoge und verfahren zu deren herstellung.
DE2534926A1 (de)	1976-02-19	Sauerstoffanaloge von cephalosporinen
DE69305904T2 (de)	1997-03-13	Benzo(b)Thiophen-5-Ylderivat und Verfahren zu seiner Herstellung
CH617205A5 (fr)	1980-05-14
DE2417987A1 (de)	1975-08-07	Cephalosporinsulfonatester und verfahren zu ihrer herstellung
DE2337105A1 (de)	1974-01-31	Antibiotika und verfahren zu ihrer herstellung
AT333948B (de)	1976-12-27	Verfahren zur herstellung von neuen ceph-3-emen und deren salzen
DE2134439A1 (de)	1972-05-25	Antibakterielle Mittel und Verfahren zu deren Herstellung
DE2721731C2 (de)	1982-12-23	Verfahren zur Herstellung eines N-geschützten Cephalosporin-C-Diesters
DE2656144C2 (de)	1985-08-29	Verfahren zur Herstellung von 3-Acyloxymethyl-2-cephemverbindungen
AT340592B (de)	1977-12-27	Verfahren zur herstellung von neuen dl-7-azidocephalosporinverbindungen
AT384215B (de)	1987-10-12	Verfahren zur herstellung von neuen, heterocyclischen essigsaeuren

Legal Events

Date	Code	Title	Description
1995-01-31	PL	Patent ceased
2024-10-31	PL	Patent ceased