CA1097613A - Ethers de la cephalosporine - Google Patents

Ethers de la cephalosporine

Info

Publication number: CA1097613A
Authority: CA; Canada
Prior art keywords: cephem; methoxy; nitrobenzyl; carboxylate; amino
Prior art date: 1973-11-26
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

Application number

CA186,688A

Other languages

English (en)

Other versions

CA186688S (en

Inventor

Robert R. Chauvette

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

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.)

1973-11-26

Filing date

1973-11-26

Publication date

1981-03-17

1973-11-26 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1973-11-26 Priority to CA186,688A priority Critical patent/CA1097613A/fr

1981-03-17 Application granted granted Critical

1981-03-17 Publication of CA1097613A publication Critical patent/CA1097613A/fr

Status Expired legal-status Critical Current

Links

-1 Cephalosporin ethers Chemical class 0.000 title claims abstract description 187
229930186147 Cephalosporin Natural products 0.000 title abstract description 28
229940124587 cephalosporin Drugs 0.000 title abstract description 28
150000001875 compounds Chemical class 0.000 claims abstract description 35
239000002253 acid Substances 0.000 claims abstract description 16
238000004519 manufacturing process Methods 0.000 claims abstract description 16
238000000034 method Methods 0.000 claims description 39
239000011541 reaction mixture Substances 0.000 claims description 38
150000002148 esters Chemical class 0.000 claims description 32
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 31
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims description 30
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 28
239000001257 hydrogen Substances 0.000 claims description 25
229910052739 hydrogen Inorganic materials 0.000 claims description 25
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
AZPOCLFVWJCXJF-SBXXRYSUSA-N (4-nitrophenyl)methyl (6r)-7-amino-3-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@H]1N2C(C1N)=O)CC(OC)=C2C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 AZPOCLFVWJCXJF-SBXXRYSUSA-N 0.000 claims description 18
150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 16
125000002252 acyl group Chemical group 0.000 claims description 15
239000012442 inert solvent Substances 0.000 claims description 15
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
CMKKEASDKHKEAE-XTBNCEIVSA-N (4-nitrophenyl)methyl (6r)-7-amino-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate;hydrochloride Chemical compound Cl.S([C@@H]1C(C(N11)=O)N)CC(O)=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 CMKKEASDKHKEAE-XTBNCEIVSA-N 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
239000000126 substance Substances 0.000 claims description 12
238000006243 chemical reaction Methods 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
230000002633 protecting effect Effects 0.000 claims description 9
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
125000003710 aryl alkyl group Chemical group 0.000 claims description 8
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
231100000252 nontoxic Toxicity 0.000 claims description 7
230000003000 nontoxic effect Effects 0.000 claims description 7
QUVSZZYBJVMBSI-UUSAFJCLSA-N (4-nitrophenyl)methyl (6r)-3-methoxy-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)OC)C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)CC1=CC=CS1 QUVSZZYBJVMBSI-UUSAFJCLSA-N 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 6
OCHRSRZESOFSFF-QOBVVAFRSA-N (6R)-7-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-3-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C([C@H](O)C1=CC=CC=C1)(=O)NC1[C@@H]2N(C(=C(CS2)OC)C(=O)O)C1=O OCHRSRZESOFSFF-QOBVVAFRSA-N 0.000 claims description 5
DPUJHFCZDZYLRW-HWZXHQHMSA-N (6r)-7-amino-3-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(OC)=C(C(O)=O)N2C(=O)C(N)[C@@H]12 DPUJHFCZDZYLRW-HWZXHQHMSA-N 0.000 claims description 5
AJYXPNIENRLELY-UHFFFAOYSA-N 2-thiophen-2-ylacetyl chloride Chemical compound ClC(=O)CC1=CC=CS1 AJYXPNIENRLELY-UHFFFAOYSA-N 0.000 claims description 5
WLXALCKAKGDNAT-UHFFFAOYSA-N diazoethane Chemical compound CC=[N+]=[N-] WLXALCKAKGDNAT-UHFFFAOYSA-N 0.000 claims description 5
150000002431 hydrogen Chemical group 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
150000003839 salts Chemical class 0.000 claims description 5
IKCXBFLZAGDTJF-FQNRMIAFSA-N (4-nitrophenyl)methyl (6R)-7-acetamido-3-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C(C)(=O)NC1[C@@H]2N(C(=C(CS2)OC)C(=O)OCC2=CC=C(C=C2)[N+](=O)[O-])C1=O IKCXBFLZAGDTJF-FQNRMIAFSA-N 0.000 claims description 4
SKVQLQRJNJCRCB-JLOHTSLTSA-N (6R)-3-methoxy-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1C(=CC=C1)CC(=O)NC1[C@@H]2N(C(=C(CS2)OC)C(=O)O)C1=O SKVQLQRJNJCRCB-JLOHTSLTSA-N 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
125000004970 halomethyl group Chemical group 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
SDLQWOIUATWYSP-WPZCJLIBSA-N (4-nitrophenyl)methyl (6r)-7-acetamido-3-hydroxy-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(O)=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 SDLQWOIUATWYSP-WPZCJLIBSA-N 0.000 claims description 3
DEEKRROIWJNPQB-ZCFIWIBFSA-N (6R)-3-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound COC=1CS[C@H]2N(C=1C(=O)O)C(C2)=O DEEKRROIWJNPQB-ZCFIWIBFSA-N 0.000 claims description 3
LRNOQSOTAKZZDT-WPZCJLIBSA-N (6r)-3-methoxy-8-oxo-7-[(2-phenoxyacetyl)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)OC)C(O)=O)NC(=O)COC1=CC=CC=C1 LRNOQSOTAKZZDT-WPZCJLIBSA-N 0.000 claims description 3
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
XPDGOAYDTHKGJD-OTOKDRCRSA-N benzhydryl (6r)-7-amino-3-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@H]1N2C(C1N)=O)CC(OC)=C2C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 XPDGOAYDTHKGJD-OTOKDRCRSA-N 0.000 claims description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical group 0.000 claims description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 3
UAOXYGYZBVWBRZ-AVKWCDSFSA-N (4-methoxyphenyl)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=CC(OC)=CC=C1COC(=O)C1=C(O)CS[C@H]2N1C(=O)C2NC(=O)COC1=CC=CC=C1 UAOXYGYZBVWBRZ-AVKWCDSFSA-N 0.000 claims description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
229930194542 Keto Natural products 0.000 claims description 2
239000012346 acetyl chloride Substances 0.000 claims description 2
125000000468 ketone group Chemical group 0.000 claims description 2
241000965481 Darksidea alpha Species 0.000 claims 8
YBADLXQNJCMBKR-UHFFFAOYSA-N (4-nitrophenyl)acetic acid Chemical group OC(=O)CC1=CC=C([N+]([O-])=O)C=C1 YBADLXQNJCMBKR-UHFFFAOYSA-N 0.000 claims 3
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 2
125000000217 alkyl group Chemical group 0.000 claims 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 claims 1
NRPFNQUDKRYCNX-UHFFFAOYSA-N 4-methoxyphenylacetic acid Chemical group COC1=CC=C(CC(O)=O)C=C1 NRPFNQUDKRYCNX-UHFFFAOYSA-N 0.000 claims 1
230000003115 biocidal effect Effects 0.000 abstract description 19
125000004185 ester group Chemical group 0.000 abstract description 7
YJZFWZGAQNTLMM-PUOGSPQQSA-N (6r)-7-amino-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(O)=C(C(O)=O)N2C(=O)C(N)[C@H]21 YJZFWZGAQNTLMM-PUOGSPQQSA-N 0.000 abstract description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
239000000243 solution Substances 0.000 description 57
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
150000001408 amides Chemical class 0.000 description 30
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 28
239000000203 mixture Substances 0.000 description 28
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
125000003118 aryl group Chemical group 0.000 description 17
229940073584 methylene chloride Drugs 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
238000010521 absorption reaction Methods 0.000 description 15
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 15
150000001780 cephalosporins Chemical class 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 13
101150041968 CDC13 gene Proteins 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
238000000921 elemental analysis Methods 0.000 description 12
239000000047 product Substances 0.000 description 12
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
239000003242 anti bacterial agent Substances 0.000 description 10
238000006266 etherification reaction Methods 0.000 description 10
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
150000008049 diazo compounds Chemical class 0.000 description 9
239000010410 layer Substances 0.000 description 9
239000007795 chemical reaction product Substances 0.000 description 8
230000010933 acylation Effects 0.000 description 7
238000005917 acylation reaction Methods 0.000 description 7
229940088710 antibiotic agent Drugs 0.000 description 7
239000000543 intermediate Substances 0.000 description 7
WURFKUQACINBSI-UHFFFAOYSA-M ozonide Chemical compound [O]O[O-] WURFKUQACINBSI-UHFFFAOYSA-M 0.000 description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229960001407 sodium bicarbonate Drugs 0.000 description 7
239000007787 solid Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
150000002170 ethers Chemical class 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
239000002904 solvent Substances 0.000 description 6
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 5
NWWJFMCCTZLKNT-UHFFFAOYSA-N 3,4-dihydro-2h-thiazine Chemical group C1CC=CSN1 NWWJFMCCTZLKNT-UHFFFAOYSA-N 0.000 description 5
238000003776 cleavage reaction Methods 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
239000012047 saturated solution Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
HOKIDJSKDBPKTQ-GLXFQSAKSA-N Cephalosporin C Natural products S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(O)=O)[C@@H]12 HOKIDJSKDBPKTQ-GLXFQSAKSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 4
208000015181 infectious disease Diseases 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
230000007017 scission Effects 0.000 description 4
239000002002 slurry Substances 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
230000000903 blocking effect Effects 0.000 description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
150000007942 carboxylates Chemical class 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
210000002966 serum Anatomy 0.000 description 3
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
230000003595 spectral effect Effects 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
238000004448 titration Methods 0.000 description 3
229940086542 triethylamine Drugs 0.000 description 3
YTCUEIOOUOMPAT-RXMQYKEDSA-N (6r)-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=C(O)CS[C@@H]2CC(=O)N12 YTCUEIOOUOMPAT-RXMQYKEDSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
241000588724 Escherichia coli Species 0.000 description 2
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 2
241000588747 Klebsiella pneumoniae Species 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
241000607715 Serratia marcescens Species 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
241000191940 Staphylococcus Species 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
ITLHXEGAYQFOHJ-UHFFFAOYSA-N [diazo(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(=[N+]=[N-])C1=CC=CC=C1 ITLHXEGAYQFOHJ-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
238000007792 addition Methods 0.000 description 2
125000005037 alkyl phenyl group Chemical group 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
125000002843 carboxylic acid group Chemical group 0.000 description 2
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 2
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150000005690 diesters Chemical class 0.000 description 1
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125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000006038 hexenyl group Chemical group 0.000 description 1
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239000012433 hydrogen halide Substances 0.000 description 1
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239000005457 ice water Substances 0.000 description 1
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INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
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239000007791 liquid phase Substances 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
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WZBRDFTXXPPTMC-WPZCJLIBSA-N 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]2SCC(O)=C(N2C1=O)C(=O)OC)NC(=O)COC1=CC=CC=C1 WZBRDFTXXPPTMC-WPZCJLIBSA-N 0.000 description 1
JGYJPCOAWXOTQY-FQNRMIAFSA-N methyl (6r)-3-methoxy-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@H]2SCC(=C(N2C1=O)C(=O)OC)OC)NC(=O)COC1=CC=CC=C1 JGYJPCOAWXOTQY-FQNRMIAFSA-N 0.000 description 1
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QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 1
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125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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125000006502 nitrobenzyl group Chemical group 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
230000009965 odorless effect Effects 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
QNXIYXGRPXRGOB-UHFFFAOYSA-N oxolane;propan-2-one Chemical compound CC(C)=O.C1CCOC1 QNXIYXGRPXRGOB-UHFFFAOYSA-N 0.000 description 1
238000005949 ozonolysis reaction Methods 0.000 description 1
125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
230000037361 pathway Effects 0.000 description 1
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
239000012071 phase Substances 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
235000014786 phosphorus Nutrition 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 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
229910000027 potassium carbonate Inorganic materials 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
239000003440 toxic substance Substances 0.000 description 1
238000001665 trituration Methods 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Landscapes

Cephalosporin Compounds (AREA)

CA186,688A 1973-11-26 1973-11-26 Ethers de la cephalosporine Expired CA1097613A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA186,688A CA1097613A (fr)	1973-11-26	1973-11-26	Ethers de la cephalosporine

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA186,688A CA1097613A (fr)	1973-11-26	1973-11-26	Ethers de la cephalosporine

Publications (1)

Publication Number	Publication Date
CA1097613A true CA1097613A (fr)	1981-03-17

Family

ID=4098498

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA186,688A Expired CA1097613A (fr)	1973-11-26	1973-11-26	Ethers de la cephalosporine

Country Status (1)

Country	Link
CA (1)	CA1097613A (fr)

1973
- 1973-11-26 CA CA186,688A patent/CA1097613A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1998-03-17	MKEX	Expiry

Publication	Publication Date	Title
US3925372A (en)	1975-12-09	Alpha-aminoacyl-3-halo cephalosporins
US3917587A (en)	1975-11-04	Cephalosporin ethers
JPS5946956B2 (ja)	1984-11-15	抗生物質の新規な中間体の製造方法
NO782866L (no)	1979-02-27	Fremgangsmaate for fremstilling av cefalosporinderivater
US3994885A (en)	1976-11-30	Process for etherifying β-lactam antibiotics
US3665003A (en)	1972-05-23	Cephalosporin compounds
US4065620A (en)	1977-12-27	3-(Substituted) vinyl cephalosporins
US3917588A (en)	1975-11-04	{60 -Aminoacyl cephalosporin ethers
US4894371A (en)	1990-01-16	3-substituted-aminomethyl cephalosporin derivatives
EP0236231A2 (fr)	1987-09-09	Dérivés de céphalosporine
GB1583039A (en)	1981-01-21	Oxazolidine compounds
US4104469A (en)	1978-08-01	7-(Syn-α-alkoxy-iminofuryl)acetamido-3-(2-methyl-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylthiomethyl)-3-cephem-4-carboxylic acids
US4059578A (en)	1977-11-22	7-Substituted mercaptoacetamido cephamycins
US4012380A (en)	1977-03-15	7-Acylamino-3-acyl-2(or 3)cephems
US4001226A (en)	1977-01-04	3-(substituted)carbonylamino cephem derivatives
CA1097613A (fr)	1981-03-17	Ethers de la cephalosporine
US4044000A (en)	1977-08-23	Substituted β-lactam antibiotics
US4145540A (en)	1979-03-20	7β-Phosphoramido-7α-methoxycephalosporanic acid derivatives
JPH04225985A (ja)	1992-08-14	セフアロスポリン化合物
US3954731A (en)	1976-05-04	Process for preparing 6-alkoxypenicillanic and 7-alkoxycephalosporin acids
US4020058A (en)	1977-04-26	Improvements in or relating to cephalosporin antibiotics
US4103085A (en)	1978-07-25	7-(Syn-α-alkoxy-iminofurylacetamido-3-(2-carboxyalkyl-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylthiomethyl)-3-cephem-4-carboxylic acids
KR870000611B1 (ko)	1987-03-25	세팔로스포린의 제조방법
US4278670A (en)	1981-07-14	7-Alpha-oxyiminoacylcephalosporins
CA1043332A (fr)	1978-11-28	3,4-dicarboxycephalosporine et ses derives