CH630924A5 - Verfahren zur herstellung von 3-chlorcephemverbindungen. - Google Patents
Verfahren zur herstellung von 3-chlorcephemverbindungen. Download PDFInfo
- Publication number
- CH630924A5 CH630924A5 CH977177A CH977177A CH630924A5 CH 630924 A5 CH630924 A5 CH 630924A5 CH 977177 A CH977177 A CH 977177A CH 977177 A CH977177 A CH 977177A CH 630924 A5 CH630924 A5 CH 630924A5
- Authority
- CH
- Switzerland
- Prior art keywords
- cephem
- hydroxy
- carboxylate
- formula
- nitrobenzyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 14
- 238000004519 manufacturing process Methods 0.000 title claims 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 90
- -1 3-chlorocephem compound Chemical class 0.000 claims description 77
- 239000000047 product Substances 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 30
- 239000011541 reaction mixture Substances 0.000 claims description 27
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- WCGNSKYKDQIREL-ZYKWQNGHSA-N (6R)-3-chloro-4-[(4-nitrophenyl)methyl]-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1=CC=C(C=C1)OCC(=O)NC2[C@@H]3N(C2=O)C(=C(C(S3)CC4=CC=C(C=C4)[N+](=O)[O-])Cl)C(=O)O WCGNSKYKDQIREL-ZYKWQNGHSA-N 0.000 claims description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 10
- 239000007858 starting material Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 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 7
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 3
- 238000005947 deacylation reaction Methods 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 239000005457 ice water Substances 0.000 claims description 2
- 239000002808 molecular sieve Substances 0.000 claims description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 150000003462 sulfoxides Chemical class 0.000 claims 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 13
- 239000000243 solution Substances 0.000 claims 13
- 150000002148 esters Chemical class 0.000 claims 9
- 239000002253 acid Substances 0.000 claims 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 7
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims 6
- 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 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 6
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 claims 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims 6
- 238000002360 preparation method Methods 0.000 claims 6
- 125000002252 acyl group Chemical group 0.000 claims 5
- 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 5
- 229910052736 halogen Inorganic materials 0.000 claims 5
- 239000002904 solvent Substances 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 239000003242 anti bacterial agent Substances 0.000 claims 4
- 229940088710 antibiotic agent Drugs 0.000 claims 4
- ZRRLCCCOCSDAKF-UHFFFAOYSA-N azetidin-2-one thionyl dichloride Chemical compound ClS(Cl)=O.O=C1CCN1 ZRRLCCCOCSDAKF-UHFFFAOYSA-N 0.000 claims 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 4
- 239000003638 chemical reducing agent Substances 0.000 claims 4
- 239000006184 cosolvent Substances 0.000 claims 4
- 238000000354 decomposition reaction Methods 0.000 claims 4
- 150000002367 halogens Chemical group 0.000 claims 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 4
- 230000003647 oxidation Effects 0.000 claims 4
- 238000007254 oxidation reaction Methods 0.000 claims 4
- 238000005949 ozonolysis reaction Methods 0.000 claims 4
- 238000007363 ring formation reaction Methods 0.000 claims 4
- OAZLXJCFUYYYGO-ZCFIWIBFSA-N (6r)-3-chloro-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC(Cl)=CN2C(=O)C[C@H]21 OAZLXJCFUYYYGO-ZCFIWIBFSA-N 0.000 claims 3
- HCXJFMDOHDNDCC-UHFFFAOYSA-N 5-$l^{1}-oxidanyl-3,4-dihydropyrrol-2-one Chemical group O=C1CCC(=O)[N]1 HCXJFMDOHDNDCC-UHFFFAOYSA-N 0.000 claims 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- 229930186147 Cephalosporin Natural products 0.000 claims 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 3
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 3
- 230000003115 biocidal effect Effects 0.000 claims 3
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- 239000003054 catalyst Substances 0.000 claims 3
- 229940124587 cephalosporin Drugs 0.000 claims 3
- 150000001780 cephalosporins Chemical class 0.000 claims 3
- 238000006243 chemical reaction Methods 0.000 claims 3
- 238000005660 chlorination reaction Methods 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- 239000001257 hydrogen Substances 0.000 claims 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 3
- 239000003960 organic solvent Substances 0.000 claims 3
- 125000005544 phthalimido group Chemical group 0.000 claims 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 3
- 239000011701 zinc Substances 0.000 claims 3
- 229910052725 zinc Inorganic materials 0.000 claims 3
- 238000005727 Friedel-Crafts reaction Methods 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 239000002841 Lewis acid Substances 0.000 claims 2
- 229930182555 Penicillin Natural products 0.000 claims 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims 2
- 238000007257 deesterification reaction Methods 0.000 claims 2
- 230000008020 evaporation Effects 0.000 claims 2
- 238000000855 fermentation Methods 0.000 claims 2
- 230000004151 fermentation Effects 0.000 claims 2
- 125000002541 furyl group Chemical group 0.000 claims 2
- 150000007517 lewis acids Chemical class 0.000 claims 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 2
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 claims 2
- 239000012044 organic layer Substances 0.000 claims 2
- 150000002960 penicillins Chemical class 0.000 claims 2
- 150000003254 radicals Chemical class 0.000 claims 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- 125000001544 thienyl group Chemical group 0.000 claims 2
- 150000003568 thioethers Chemical class 0.000 claims 2
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 claims 1
- GVVFCAFBYHYGEE-OGFXRTJISA-N (2r)-2-amino-2-phenylacetyl chloride;hydron;chloride Chemical compound Cl.ClC(=O)[C@H](N)C1=CC=CC=C1 GVVFCAFBYHYGEE-OGFXRTJISA-N 0.000 claims 1
- CCJOUTTZYREJDY-AVKWCDSFSA-N (4-nitrophenyl)methyl (6r)-3-hydroxy-7-[[2-(4-methoxyphenyl)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC(OC)=CC=C1CC(=O)NC1C(=O)N2C(C(=O)OCC=3C=CC(=CC=3)[N+]([O-])=O)=C(O)CS[C@@H]21 CCJOUTTZYREJDY-AVKWCDSFSA-N 0.000 claims 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 claims 1
- IHHXXDQLPNEPCK-ZYKWQNGHSA-N (6R)-3-chloro-4-[(4-nitrophenyl)methyl]-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1=CC=C(C=C1)CC(=O)NC2[C@@H]3N(C2=O)C(=C(C(S3)CC4=CC=C(C=C4)[N+](=O)[O-])Cl)C(=O)O IHHXXDQLPNEPCK-ZYKWQNGHSA-N 0.000 claims 1
- ZMPANRXWKQKPAE-FWXSHLFISA-N (6R)-3-hydroxy-4-[(4-methoxyphenyl)methyl]-8-oxo-7-(propanoylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CCC(=O)NC1[C@@H]2N(C1=O)C(=C(C(S2)CC3=CC=C(C=C3)OC)O)C(=O)O ZMPANRXWKQKPAE-FWXSHLFISA-N 0.000 claims 1
- XGDYITGJAYSEMC-CWZMJNCASA-N (6R)-3-hydroxy-4-[(4-methoxyphenyl)methyl]-8-oxo-7-[(2-phenylacetyl)amino]-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)CC4=CC=CC=C4)C(=O)O)O XGDYITGJAYSEMC-CWZMJNCASA-N 0.000 claims 1
- ARXCQCNOQIGXDG-CBQMELLWSA-N (6R)-3-hydroxy-4-[(4-nitrophenyl)methyl]-5,8-dioxo-7-[(2-phenoxyacetyl)amino]-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1=CC=C(C=C1)OCC(=O)NC2[C@@H]3N(C2=O)C(=C(C(S3=O)CC4=CC=C(C=C4)[N+](=O)[O-])O)C(=O)O ARXCQCNOQIGXDG-CBQMELLWSA-N 0.000 claims 1
- VNKXHAYGYXURIR-AEJJIKPWSA-N (6R)-3-hydroxy-4-[(4-nitrophenyl)methyl]-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1=CC=C(C=C1)CC(=O)NC2[C@@H]3N(C2=O)C(=C(C(S3)CC4=CC=C(C=C4)[N+](=O)[O-])O)C(=O)O VNKXHAYGYXURIR-AEJJIKPWSA-N 0.000 claims 1
- HFRVTMJPODYOHU-TYJKZOGGSA-N (6R)-3-hydroxy-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 C1=CSC(=C1)CC(=O)NC2[C@@H]3N(C2=O)C(=C(C(S3)CC4=CC=C(C=C4)[N+](=O)[O-])O)C(=O)O HFRVTMJPODYOHU-TYJKZOGGSA-N 0.000 claims 1
- YPQWGCVDSLHHPK-QKFMDRJYSA-N (6R)-7-acetamido-3-hydroxy-4-[(4-nitrophenyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC(=O)NC1[C@@H]2N(C1=O)C(=C(C(S2)CC3=CC=C(C=C3)[N+](=O)[O-])O)C(=O)O YPQWGCVDSLHHPK-QKFMDRJYSA-N 0.000 claims 1
- PLZKGMHUMRPJIC-NODKNVJMSA-N (6R)-7-benzamido-3-hydroxy-4-[(4-nitrophenyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1=CC=C(C=C1)C(=O)NC2[C@@H]3N(C2=O)C(=C(C(S3)CC4=CC=C(C=C4)[N+](=O)[O-])O)C(=O)O PLZKGMHUMRPJIC-NODKNVJMSA-N 0.000 claims 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 claims 1
- FZEVMBJWXHDLDB-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical group S1CC=CN2C(=O)C[C@H]21 FZEVMBJWXHDLDB-ZCFIWIBFSA-N 0.000 claims 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims 1
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 claims 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 claims 1
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- 208000035473 Communicable disease Diseases 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 claims 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 150000001298 alcohols Chemical class 0.000 claims 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 239000003125 aqueous solvent Substances 0.000 claims 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims 1
- 208000022362 bacterial infectious disease Diseases 0.000 claims 1
- WQNPYTGUDVXQTO-IQHZPMLTSA-N benzhydryl (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)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(=O)COC1=CC=CC=C1 WQNPYTGUDVXQTO-IQHZPMLTSA-N 0.000 claims 1
- HJINVAQLVZRFTL-IQHZPMLTSA-N benzhydryl (6r)-3-hydroxy-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)O)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(=O)CC1=CC=CC=C1 HJINVAQLVZRFTL-IQHZPMLTSA-N 0.000 claims 1
- HFJCJTYHTNBAKL-UIDYPRJRSA-N benzhydryl (6r)-7-[[2-(furan-2-yl)acetyl]amino]-3-hydroxy-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)O)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(=O)CC1=CC=CO1 HFJCJTYHTNBAKL-UIDYPRJRSA-N 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- ZJQQFXKYQHHEOF-FBLFFUNLSA-N benzyl (6r)-7-(1,3-dioxoisoindol-2-yl)-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@H]1N2C(C1N1C(C3=CC=CC=C3C1=O)=O)=O)CC(O)=C2C(=O)OCC1=CC=CC=C1 ZJQQFXKYQHHEOF-FBLFFUNLSA-N 0.000 claims 1
- OFDMJVKKPOXNPE-LRTDYKAYSA-N benzyl (6r)-7-[[2-(furan-2-yl)acetyl]amino]-3-hydroxy-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)O)C(=O)OCC=1C=CC=CC=1)NC(=O)CC1=CC=CO1 OFDMJVKKPOXNPE-LRTDYKAYSA-N 0.000 claims 1
- WCNMKKIIMHPROX-WPZCJLIBSA-N benzyl (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=CC=C1 WCNMKKIIMHPROX-WPZCJLIBSA-N 0.000 claims 1
- 239000004305 biphenyl Chemical group 0.000 claims 1
- 235000010290 biphenyl Nutrition 0.000 claims 1
- 125000006267 biphenyl group Chemical group 0.000 claims 1
- 238000009835 boiling Methods 0.000 claims 1
- 239000012267 brine Substances 0.000 claims 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 150000001721 carbon Chemical group 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 238000003776 cleavage reaction Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 238000005868 electrolysis reaction Methods 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 238000000605 extraction Methods 0.000 claims 1
- 235000019253 formic acid Nutrition 0.000 claims 1
- 150000008282 halocarbons Chemical class 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 238000007327 hydrogenolysis reaction Methods 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims 1
- 229940050176 methyl chloride Drugs 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 150000002825 nitriles Chemical class 0.000 claims 1
- 239000003921 oil Substances 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 claims 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims 1
- VQPJTCXWTUMDBH-AVKWCDSFSA-N phenacyl (6r)-7-[[2-(4-chlorophenyl)acetyl]amino]-3-hydroxy-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)O)C(=O)OCC(=O)C=1C=CC=CC=1)NC(=O)CC1=CC=C(Cl)C=C1 VQPJTCXWTUMDBH-AVKWCDSFSA-N 0.000 claims 1
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 claims 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 1
- 239000002244 precipitate Substances 0.000 claims 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 238000011946 reduction process Methods 0.000 claims 1
- 238000010992 reflux Methods 0.000 claims 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- LFBBSWBQNQXKPF-LQDWTQKMSA-M sodium;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenoxyacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Na+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 LFBBSWBQNQXKPF-LQDWTQKMSA-M 0.000 claims 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims 1
- 239000001119 stannous chloride Substances 0.000 claims 1
- 235000011150 stannous chloride Nutrition 0.000 claims 1
- 238000003860 storage Methods 0.000 claims 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 claims 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 claims 1
- 229940102001 zinc bromide Drugs 0.000 claims 1
- 235000005074 zinc chloride Nutrition 0.000 claims 1
- 239000011592 zinc chloride Substances 0.000 claims 1
- DUNKXUFBGCUVQW-UHFFFAOYSA-J zirconium tetrachloride Chemical compound Cl[Zr](Cl)(Cl)Cl DUNKXUFBGCUVQW-UHFFFAOYSA-J 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 3
- ZRIRHXUOQLQRPW-KDDGLUCOSA-N (6R)-3-chloro-7-(1,3-dioxoisoindol-2-yl)-4-[(4-nitrophenyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1=CC=C2C(=C1)C(=O)N(C2=O)C3[C@@H]4N(C3=O)C(=C(C(S4)CC5=CC=C(C=C5)[N+](=O)[O-])Cl)C(=O)O ZRIRHXUOQLQRPW-KDDGLUCOSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- QHTOIDKCEPKVCM-ZCFIWIBFSA-N cepham Chemical compound S1CCCN2C(=O)C[C@H]21 QHTOIDKCEPKVCM-ZCFIWIBFSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 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
- C07D501/14—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 |
|---|---|---|---|
| US71494876A | 1976-08-16 | 1976-08-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH630924A5 true CH630924A5 (de) | 1982-07-15 |
Family
ID=24872131
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH977177A CH630924A5 (de) | 1976-08-16 | 1977-08-09 | Verfahren zur herstellung von 3-chlorcephemverbindungen. |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US4115643A (en, 2012) |
| JP (1) | JPS5323994A (en, 2012) |
| BE (1) | BE857244A (en, 2012) |
| BG (1) | BG28068A3 (en, 2012) |
| CA (1) | CA1099256A (en, 2012) |
| CH (1) | CH630924A5 (en, 2012) |
| CS (1) | CS192588B2 (en, 2012) |
| DD (1) | DD131858A5 (en, 2012) |
| DE (1) | DE2735454A1 (en, 2012) |
| ES (1) | ES461587A1 (en, 2012) |
| FI (1) | FI66873C (en, 2012) |
| FR (1) | FR2362145A1 (en, 2012) |
| GB (1) | GB1582044A (en, 2012) |
| HU (1) | HU179459B (en, 2012) |
| IE (1) | IE45158B1 (en, 2012) |
| IL (1) | IL52416A (en, 2012) |
| NL (1) | NL7709055A (en, 2012) |
| PL (1) | PL110242B1 (en, 2012) |
| RO (1) | RO71908A (en, 2012) |
| SU (1) | SU1018586A3 (en, 2012) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT342197B (de) * | 1975-02-20 | 1978-03-28 | Ciba Geigy Ag | Neues verfahren zur herstellung von 3-cephemverbindungen |
| US4226986A (en) * | 1979-02-01 | 1980-10-07 | Eli Lilly And Company | Process for halogenation of β-lactam compounds |
| US4223133A (en) * | 1979-02-01 | 1980-09-16 | Eli Lilly And Company | Cephalosporin reduction process |
| US4271305A (en) * | 1979-02-01 | 1981-06-02 | Eli Lilly And Company | Thiazolinoazetidinones and process therefor |
| US4237279A (en) * | 1979-07-27 | 1980-12-02 | Eli Lilly And Company | Crystalline 3-hydroxycephalosporin solvates |
| US4281117A (en) * | 1980-09-04 | 1981-07-28 | Eli Lilly And Company | Process for 3-chloro cephalosporin nucleus |
| US5159071A (en) * | 1990-09-06 | 1992-10-27 | Ranbaxy Laboratories Limited | Process for the manufacture of 7-amino-3-exomethylene-3-cepham-4-carboxylic acid ester |
| US5350845A (en) * | 1992-04-08 | 1994-09-27 | Eli Lilly And Company | Process for preparing 7-substituted-amino-3-hydroxy-3-cephem-4-protected carboxy-sulfoxide esters |
| IN181695B (en, 2012) * | 1992-08-10 | 1998-09-05 | Ranbaxy Lab Ltd | |
| US5604222A (en) * | 1993-12-27 | 1997-02-18 | Lupin Laboratories, Ltd. | Method for the preparation of 2-chloro sulfinyl azetidinones |
| US5578721A (en) * | 1994-07-11 | 1996-11-26 | Lupin Laboratories Limited | Process for preparation of 3-exomethylene cepham sulfoxide esters |
| KR100390551B1 (ko) * | 1996-08-22 | 2003-11-17 | 주식회사 코오롱 | 3-할로메틸-3-세펨-4-카르복실레이트 1-옥사이드의 제조방법 |
| CN101190921B (zh) * | 2007-11-27 | 2010-05-19 | 吉林省石油化工设计研究院 | 一种对硝基苄基-7-苯氧基乙酰胺-3-外亚甲基头孢-4-羧酸酯-1-β-氧化物制备方法 |
| CN102443014B (zh) * | 2011-12-29 | 2014-07-09 | 上海右手医药科技开发有限公司 | 3-氯头孢菌素衍生物及其合成方法与在头孢克洛制备中的应用 |
| CN103588790A (zh) * | 2013-11-29 | 2014-02-19 | 中国科学院长春应用化学研究所 | 7-氨基-3-氯-3-头孢-4-羧酸-对硝基苄基酯的制备方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3641014A (en) * | 1968-10-03 | 1972-02-08 | Lilly Co Eli | Reduction of delta**3-cephalosporin sulfoxides |
| AR208068A1 (es) * | 1973-02-23 | 1976-11-30 | Lilly Co Eli | Un procedimiento para preparar derivados de acidos 7-acilamido-3-halo-cefem-4-carboxilico los esteres y las sales farmaceuticamente aceptables de los mismos |
| US3925372A (en) * | 1973-02-23 | 1975-12-09 | Lilly Co Eli | Alpha-aminoacyl-3-halo cephalosporins |
| US3962227A (en) * | 1973-02-23 | 1976-06-08 | Eli Lilly And Company | 3-halo cephalosporins |
| YU36970B (en) * | 1973-02-23 | 1984-08-31 | Lilly Co Eli | Process for obtaining 7-(amino)-acylamido-3-halocephalosporins |
-
1977
- 1977-06-28 IE IE1320/77A patent/IE45158B1/en not_active IP Right Cessation
- 1977-06-29 IL IL52416A patent/IL52416A/xx unknown
- 1977-07-18 CA CA282,954A patent/CA1099256A/en not_active Expired
- 1977-07-22 BG BG036981A patent/BG28068A3/xx unknown
- 1977-07-28 BE BE1008305A patent/BE857244A/xx not_active IP Right Cessation
- 1977-07-28 FR FR7723211A patent/FR2362145A1/fr active Granted
- 1977-08-01 FI FI772339A patent/FI66873C/fi not_active IP Right Cessation
- 1977-08-05 DE DE19772735454 patent/DE2735454A1/de active Granted
- 1977-08-08 US US05/822,472 patent/US4115643A/en not_active Expired - Lifetime
- 1977-08-09 CH CH977177A patent/CH630924A5/de not_active IP Right Cessation
- 1977-08-10 GB GB33451/77A patent/GB1582044A/en not_active Expired
- 1977-08-12 ES ES461587A patent/ES461587A1/es not_active Expired
- 1977-08-15 RO RO7791365A patent/RO71908A/ro unknown
- 1977-08-15 PL PL1977200289A patent/PL110242B1/pl not_active IP Right Cessation
- 1977-08-15 SU SU772511154A patent/SU1018586A3/ru active
- 1977-08-15 HU HU77EI758A patent/HU179459B/hu unknown
- 1977-08-16 NL NL7709055A patent/NL7709055A/xx not_active Application Discontinuation
- 1977-08-16 DD DD7700200594A patent/DD131858A5/xx unknown
- 1977-08-16 CS CS775383A patent/CS192588B2/cs unknown
- 1977-08-16 JP JP9817777A patent/JPS5323994A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| PL200289A1 (pl) | 1978-05-08 |
| PL110242B1 (en) | 1980-07-31 |
| JPS6120556B2 (en, 2012) | 1986-05-22 |
| FI66873C (fi) | 1984-12-10 |
| IL52416A (en) | 1980-02-29 |
| FI66873B (fi) | 1984-08-31 |
| ES461587A1 (es) | 1978-06-01 |
| JPS5323994A (en) | 1978-03-06 |
| DE2735454C2 (en, 2012) | 1992-12-10 |
| US4115643A (en) | 1978-09-19 |
| BE857244A (fr) | 1978-01-30 |
| FR2362145B1 (en, 2012) | 1980-02-15 |
| CS192588B2 (en) | 1979-08-31 |
| GB1582044A (en) | 1980-12-31 |
| IE45158B1 (en) | 1982-06-30 |
| FR2362145A1 (fr) | 1978-03-17 |
| DD131858A5 (de) | 1978-07-26 |
| IL52416A0 (en) | 1977-08-31 |
| HU179459B (en) | 1982-10-28 |
| RO71908A (ro) | 1981-11-24 |
| BG28068A3 (bg) | 1980-02-25 |
| NL7709055A (nl) | 1978-02-20 |
| CA1099256A (en) | 1981-04-14 |
| DE2735454A1 (de) | 1978-02-23 |
| SU1018586A3 (ru) | 1983-05-15 |
| FI772339A7 (fi) | 1978-02-17 |
| IE45158L (en) | 1978-02-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |