CA1175807A - 2.beta.-CHLOROMETHYL-2.alpha.-METHYLPENAM-3.alpha.-CARBOXYLIC ACID SULFONE - Google Patents

2.beta.-CHLOROMETHYL-2.alpha.-METHYLPENAM-3.alpha.-CARBOXYLIC ACID SULFONE

Info

Publication number: CA1175807A
Authority: CA; Canada
Prior art keywords: acid; ester; salt; formula; produce
Prior art date: 1980-01-21
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

CA000368537A

Other languages

English (en)

French (fr)

Inventor

William J. Gottstein

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.)

Bristol Myers Squibb Co

Original Assignee

Bristol Myers Squibb 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.)

1980-01-21

Filing date

1981-01-15

Publication date

1984-10-09

1980-12-11 Priority claimed from US06/214,833 external-priority patent/US4340539A/en

1981-01-15 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

1983-03-24 Priority to CA000424446A priority Critical patent/CA1175808A/en

1983-04-19 Priority to CA000426209A priority patent/CA1175809A/en

1984-10-09 Application granted granted Critical

1984-10-09 Publication of CA1175807A publication Critical patent/CA1175807A/en

Status Expired legal-status Critical Current

Links

150000002148 esters Chemical class 0.000 claims abstract description 43
150000003839 salts Chemical class 0.000 claims abstract description 37
239000002253 acid Substances 0.000 claims description 75
-1 ester sulfoxide Chemical class 0.000 claims description 51
238000000034 method Methods 0.000 claims description 36
150000001875 compounds Chemical class 0.000 claims description 30
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 16
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 11
239000003054 catalyst Substances 0.000 claims description 8
229960000583 acetic acid Drugs 0.000 claims description 7
230000001590 oxidative effect Effects 0.000 claims description 6
229910052763 palladium Inorganic materials 0.000 claims description 6
239000012286 potassium permanganate Substances 0.000 claims description 6
239000000126 substance Substances 0.000 claims description 6
239000012362 glacial acetic acid Substances 0.000 claims description 5
238000005984 hydrogenation reaction Methods 0.000 claims description 5
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 5
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
229910052751 metal Inorganic materials 0.000 claims description 4
239000002184 metal Substances 0.000 claims description 4
230000003647 oxidation Effects 0.000 claims description 4
238000007254 oxidation reaction Methods 0.000 claims description 4
239000011701 zinc Substances 0.000 claims description 4
239000007800 oxidant agent Substances 0.000 claims description 3
150000002978 peroxides Chemical group 0.000 claims description 3
229910052725 zinc Inorganic materials 0.000 claims description 3
150000004967 organic peroxy acids Chemical class 0.000 claims description 2
150000004965 peroxy acids Chemical class 0.000 claims description 2
229910052783 alkali metal Inorganic materials 0.000 claims 1
150000001340 alkali metals Chemical class 0.000 claims 1
239000003112 inhibitor Substances 0.000 abstract description 4
230000003389 potentiating effect Effects 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 134
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 90
239000000243 solution Substances 0.000 description 64
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
239000000203 mixture Substances 0.000 description 55
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
229940093499 ethyl acetate Drugs 0.000 description 46
235000019439 ethyl acetate Nutrition 0.000 description 44
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
GMJQFFRLFJLBSC-XJNRBXITSA-M potassium;(2s,3s,5r)-3-(chloromethyl)-3-methyl-4,4,7-trioxo-4$l^{6}-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [K+].O=S1(=O)[C@](C)(CCl)[C@H](C([O-])=O)N2C(=O)C[C@H]21 GMJQFFRLFJLBSC-XJNRBXITSA-M 0.000 description 37
238000001914 filtration Methods 0.000 description 24
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 22
239000000047 product Substances 0.000 description 22
238000003756 stirring Methods 0.000 description 22
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
239000007787 solid Substances 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 17
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
239000000706 filtrate Substances 0.000 description 15
229920006395 saturated elastomer Polymers 0.000 description 15
239000011734 sodium Substances 0.000 description 15
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 14
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 14
239000010410 layer Substances 0.000 description 14
239000011591 potassium Substances 0.000 description 14
229910052700 potassium Inorganic materials 0.000 description 14
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
229910052938 sodium sulfate Inorganic materials 0.000 description 13
235000011152 sodium sulphate Nutrition 0.000 description 13
150000003462 sulfoxides Chemical class 0.000 description 13
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 12
229910052708 sodium Inorganic materials 0.000 description 12
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
239000001257 hydrogen Substances 0.000 description 11
229910052739 hydrogen Inorganic materials 0.000 description 11
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 10
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
239000002002 slurry Substances 0.000 description 10
150000003457 sulfones Chemical class 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 8
239000000284 extract Substances 0.000 description 8
239000000843 powder Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
239000002904 solvent Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
230000003115 biocidal effect Effects 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
238000001228 spectrum Methods 0.000 description 7
241000894006 Bacteria Species 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
229940123930 Lactamase inhibitor Drugs 0.000 description 6
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 6
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 6
229960003022 amoxicillin Drugs 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
230000000694 effects Effects 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
238000004519 manufacturing process Methods 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
239000005909 Kieselgur Substances 0.000 description 5
125000000217 alkyl group Chemical group 0.000 description 5
150000003863 ammonium salts Chemical class 0.000 description 5
125000003118 aryl group Chemical group 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
229940125898 compound 5 Drugs 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000013078 crystal Substances 0.000 description 5
238000001035 drying Methods 0.000 description 5
150000002431 hydrogen Chemical class 0.000 description 5
239000000463 material Substances 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-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
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
229910000147 aluminium phosphate Inorganic materials 0.000 description 4
239000003242 anti bacterial agent Substances 0.000 description 4
125000003710 aryl alkyl group Chemical group 0.000 description 4
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
239000003782 beta lactam antibiotic agent Substances 0.000 description 4
229960004292 ceforanide Drugs 0.000 description 4
125000001309 chloro group Chemical group Cl* 0.000 description 4
GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
150000002500 ions Chemical class 0.000 description 4
239000011777 magnesium Substances 0.000 description 4
229910052749 magnesium Inorganic materials 0.000 description 4
NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
239000012071 phase Substances 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
235000009518 sodium iodide Nutrition 0.000 description 4
239000008279 sol Substances 0.000 description 4
239000012258 stirred mixture Substances 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 3
229960000723 ampicillin Drugs 0.000 description 3
229940088710 antibiotic agent Drugs 0.000 description 3
238000009835 boiling Methods 0.000 description 3
SLAYUXIURFNXPG-CRAIPNDOSA-N ceforanide Chemical compound NCC1=CC=CC=C1CC(=O)N[C@@H]1C(=O)N2C(C(O)=O)=C(CSC=3N(N=NN=3)CC(O)=O)CS[C@@H]21 SLAYUXIURFNXPG-CRAIPNDOSA-N 0.000 description 3
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
DLLJVQNYBYOKGS-UHFFFAOYSA-N ethoxyethane;pentane Chemical compound CCCCC.CCOCC DLLJVQNYBYOKGS-UHFFFAOYSA-N 0.000 description 3
239000002024 ethyl acetate extract Substances 0.000 description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 3
230000007935 neutral effect Effects 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
229940002612 prodrug Drugs 0.000 description 3
239000000651 prodrug Substances 0.000 description 3
238000006748 scratching Methods 0.000 description 3
230000002393 scratching effect Effects 0.000 description 3
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 2
WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 2
LXUNKDFIOZFCAK-UHFFFAOYSA-N 2-ethylhexanoic acid;potassium Chemical compound [K].CCCCC(CC)C(O)=O LXUNKDFIOZFCAK-UHFFFAOYSA-N 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
208000035143 Bacterial infection Diseases 0.000 description 2
241000606125 Bacteroides Species 0.000 description 2
125000006414 CCl Chemical group ClC* 0.000 description 2
229930186147 Cephalosporin Chemical class 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
241000588697 Enterobacter cloacae Species 0.000 description 2
241000588724 Escherichia coli Species 0.000 description 2
WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
229920005654 Sephadex Polymers 0.000 description 2
239000012507 Sephadex™ Substances 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
239000008272 agar Substances 0.000 description 2
238000013019 agitation Methods 0.000 description 2
239000003513 alkali Substances 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
208000022362 bacterial infectious disease Diseases 0.000 description 2
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Inorganic materials [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
MTRNNCLQPVCDLF-UHFFFAOYSA-N benzyl-[2-(benzylazaniumyl)ethyl]azanium;diacetate Chemical compound CC(O)=O.CC(O)=O.C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 MTRNNCLQPVCDLF-UHFFFAOYSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000002775 capsule Substances 0.000 description 2
229940124587 cephalosporin Drugs 0.000 description 2
150000001780 cephalosporins Chemical class 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
239000012467 final product Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Steroid Compounds (AREA)
Cephalosporin Compounds (AREA)

CA000368537A 1980-01-21 1981-01-15 2.beta.-CHLOROMETHYL-2.alpha.-METHYLPENAM-3.alpha.-CARBOXYLIC ACID SULFONE Expired CA1175807A (en)

Priority Applications (2)

Application Number	Priority Date	Filing Date	Title
CA000424446A CA1175808A (en)	1980-01-21	1983-03-24	2.beta.-CHLOROMETHYL-2.alpha.-METHYLPENOM-3.alpha.-CARBOXYLIC ACID SULFONE DERIVATIVES
CA000426209A CA1175809A (en)	1980-01-21	1983-04-19	2.beta.-CHLOROMETHYL-2.alpha.-METHYLPENAM-3.alpha.-CARBOXYLIC ACID SULFONE AND SALTS AND ESTERS THEREOF

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
US11389480A	1980-01-21	1980-01-21
US113,894		1980-01-21
US21483180A	1980-12-11	1980-12-11
US214,833		1980-12-11
US214,831		1980-12-11
US06/214,833 US4340539A (en)	1980-01-21	1980-12-11	Derivatives of 6-bromo penicillanic acid

Related Child Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000426209A Division CA1175809A (en)	1980-01-21	1983-04-19	2.beta.-CHLOROMETHYL-2.alpha.-METHYLPENAM-3.alpha.-CARBOXYLIC ACID SULFONE AND SALTS AND ESTERS THEREOF

Publications (1)

Publication Number	Publication Date
CA1175807A true CA1175807A (en)	1984-10-09

Family

ID=27381401

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000368537A Expired CA1175807A (en)	1980-01-21	1981-01-15	2.beta.-CHLOROMETHYL-2.alpha.-METHYLPENAM-3.alpha.-CARBOXYLIC ACID SULFONE

Country Status (12)

Country	Link
KR (1)	KR850001066B1 (da)
CA (1)	CA1175807A (da)
CH (2)	CH651571A5 (da)
DE (1)	DE3101527A1 (da)
DK (3)	DK162717C (da)
GB (1)	GB2070592B (da)
HU (2)	HU188606B (da)
IL (1)	IL61880A (da)
NL (1)	NL8100209A (da)
NO (5)	NO160298C (da)
OA (1)	OA06748A (da)
SE (5)	SE455702B (da)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ZA826687B (en) *	1981-09-14	1983-07-27	Pfizer	Beta-lactamase inhibiting 2-beta-substituted-2-alpha-methyl 5(r)penam-3-alpha-carboxylic acid 1,1-dioxides and intermediates therefor
ATE27772T1 (de) *	1983-09-15	1987-07-15	Bristol Myers Co	Pharmazeutische zusammensetzungen zur bekaempfung des widerstands von bakterien enthaltenden anaerobien.
GB2157286B (en) *	1984-04-12	1987-12-31	Leo Pharm Prod Ltd	B-lactam antibiotic potentiators

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IN149747B (da) *	1977-06-07	1982-04-03	Pfizer
DE2912511C2 (de) *	1977-06-07	1982-06-24	Pfizer Inc., 10017 New York, N.Y.	Pharmazeutische Zusammensetzung, enthaltend Penicillansäure
IE49881B1 (en) *	1979-02-13	1986-01-08	Leo Pharm Prod Ltd	B-lactam intermediates
GB2045236A (en) *	1979-03-26	1980-10-29	Hoechst Uk Ltd	Oxapenem derivatives
US4244951A (en) *	1979-05-16	1981-01-13	Pfizer Inc.	Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide

1981
- 1981-01-08 IL IL61880A patent/IL61880A/xx unknown
- 1981-01-15 CA CA000368537A patent/CA1175807A/en not_active Expired
- 1981-01-16 NL NL8100209A patent/NL8100209A/xx not_active Application Discontinuation
- 1981-01-16 GB GB8101365A patent/GB2070592B/en not_active Expired
- 1981-01-19 DE DE19813101527 patent/DE3101527A1/de not_active Withdrawn
- 1981-01-19 DK DK021881A patent/DK162717C/da not_active IP Right Cessation
- 1981-01-20 NO NO810166A patent/NO160298C/no unknown
- 1981-01-20 HU HU833171A patent/HU188606B/hu not_active IP Right Cessation
- 1981-01-20 HU HU81115A patent/HU184380B/hu not_active IP Right Cessation
- 1981-01-21 SE SE8100339A patent/SE455702B/sv not_active IP Right Cessation
- 1981-01-21 CH CH374/81A patent/CH651571A5/de not_active IP Right Cessation
- 1981-01-21 CH CH1284/84A patent/CH649087A5/de not_active IP Right Cessation
- 1981-02-19 OA OA57331A patent/OA06748A/xx unknown
1984
- 1984-07-21 KR KR1019840004326A patent/KR850001066B1/ko not_active Expired
1985
- 1985-05-08 SE SE8502285A patent/SE8502285L/xx not_active Application Discontinuation
- 1985-05-08 SE SE8502286A patent/SE466203B/sv not_active IP Right Cessation
- 1985-09-03 NO NO85853450A patent/NO161677C/no unknown
1986
- 1986-05-16 NO NO86861946A patent/NO164300C/no unknown
- 1986-05-16 NO NO86861944A patent/NO164298C/no unknown
- 1986-05-16 NO NO86861945A patent/NO164299C/no unknown
1990
- 1990-01-19 SE SE9000189A patent/SE9000189L/xx not_active Application Discontinuation
- 1990-01-19 SE SE9000190A patent/SE9000190L/xx not_active Application Discontinuation
- 1990-11-30 DK DK285890A patent/DK164938C/da not_active IP Right Cessation
- 1990-11-30 DK DK285790A patent/DK162769C/da not_active IP Right Cessation

Also Published As

Publication number	Publication date
NO161677C (no)	1989-09-13
NO861945L (no)	1981-07-22
GB2070592A (en)	1981-09-09
DK285890D0 (da)	1990-11-30
DK21881A (da)	1981-07-22
NO861944L (no)	1981-07-22
NO160298B (no)	1988-12-27
OA06748A (fr)	1982-06-30
DE3101527A1 (de)	1982-02-18
SE9000190L (sv)	1991-07-20
NO810166L (no)	1981-07-22
NO861946L (no)	1981-07-22
DK164938B (da)	1992-09-14
SE8502286D0 (sv)	1985-05-08
SE9000189D0 (sv)	1990-01-19
SE455702B (sv)	1988-08-01
NO160298C (no)	1989-04-05
DK285890A (da)	1990-11-30
HU184380B (en)	1984-08-28
NL8100209A (nl)	1981-08-17
NO164298C (no)	1990-09-19
SE8502285D0 (sv)	1985-05-08
NO853450L (no)	1981-07-22
NO161677B (no)	1989-06-05
CH651571A5 (de)	1985-09-30
SE8502285L (sv)	1985-05-08
SE8100339L (sv)	1981-09-01
SE9000190D0 (sv)	1990-01-19
NO164298B (no)	1990-06-11
HU188606B (en)	1986-04-28
NO164300B (no)	1990-06-11
SE8502286L (sv)	1985-05-08
NO164300C (no)	1990-09-19
GB2070592B (en)	1983-05-11
SE466203B (sv)	1992-01-13
KR850001066B1 (ko)	1985-07-25
DK162717B (da)	1991-12-02
KR850001465A (ko)	1985-03-18
DK164938C (da)	1993-02-01
DK285790A (da)	1990-11-30
DK162769B (da)	1991-12-09
IL61880A (en)	1984-11-30
NO164299C (no)	1990-09-19
NO164299B (no)	1990-06-11
SE9000189L (sv)	1991-07-20
DK162717C (da)	1992-04-21
DK162769C (da)	1992-04-27
DK285790D0 (da)	1990-11-30
CH649087A5 (de)	1985-04-30

Legal Events

Date	Code	Title	Description
2001-10-09	MKEX	Expiry

Publication	Publication Date	Title
CY1205A (en)	1983-12-31	Penicillin derivatives
JPS5946955B2 (ja)	1984-11-15	抗生物質の新規中間体の製造方法
JPS63146863A (ja)	1988-06-18	カルボン酸類
US4155912A (en)	1979-05-22	2-Methylpenem-3-carboxylic acid antibiotics
CA1175807A (en)	1984-10-09	2.beta.-CHLOROMETHYL-2.alpha.-METHYLPENAM-3.alpha.-CARBOXYLIC ACID SULFONE
CA1281319C (en)	1991-03-12	2.beta.-SUBSTITUTED THIOMETHYLPENICILLIN DERIVATIVES AND THEIR PREPARATION AND USE
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
US4880798A (en)	1989-11-14	Cephalosporin derivatives
KR850001339B1 (ko)	1985-09-19	페니실란산 1,1-디옥사이드 및 그의 에스테르의 제조방법
JPS6143357B2 (da)	1986-09-26
US5580865A (en)	1996-12-03	2,2-disubstituted cephem sulphones
US4340539A (en)	1982-07-20	Derivatives of 6-bromo penicillanic acid
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
US4380512A (en)	1983-04-19	2β-Chloromethyl-2α-methylpenam-3α-carboxylic acid sulfone and salts and esters thereof
KR840002214B1 (ko)	1984-12-03	2β-클로로메틸-2α-메틸페남-3α-카르복실산 술폰, 염 또는 그의 에스테르의 제조방법
IE831945L (en)	1984-05-15	Bis-esters of 4,5-di (hydroxymethyl)-2-oxo-1, 3 dioxoles.
CA1165759A (en)	1984-04-17	7.alpha.-METHOXYCEPHALOSPORIN DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND ANTIBACTERIAL DRUGS CONTAINING THE SAME
US3316273A (en)	1967-04-25	Penicillin aldehydes
CA1175809A (en)	1984-10-09	2.beta.-CHLOROMETHYL-2.alpha.-METHYLPENAM-3.alpha.-CARBOXYLIC ACID SULFONE AND SALTS AND ESTERS THEREOF
CA1175808A (en)	1984-10-09	2.beta.-CHLOROMETHYL-2.alpha.-METHYLPENOM-3.alpha.-CARBOXYLIC ACID SULFONE DERIVATIVES
JPS6145993B2 (da)	1986-10-11
GB2043635A (en)	1980-10-08	Quinoline derivatives
US4285939A (en)	1981-08-25	Cephalosporin derivatives, and antibacterial drugs containing the derivatives
GB1599611A (en)	1981-10-07	Cephalosporin derivatives
US3950350A (en)	1976-04-13	Penam-dimethylsulfoxide complex