DD236735A5 - Verfahren zur herstellung von cephalosporinverbindungen - Google Patents
Verfahren zur herstellung von cephalosporinverbindungen Download PDFInfo
- Publication number
- DD236735A5 DD236735A5 DD85274832A DD27483285A DD236735A5 DD 236735 A5 DD236735 A5 DD 236735A5 DD 85274832 A DD85274832 A DD 85274832A DD 27483285 A DD27483285 A DD 27483285A DD 236735 A5 DD236735 A5 DD 236735A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- amino
- thiadiazol
- cephem
- carboxylate
- group
- Prior art date
Links
- -1 CEPHALOSPORIN COMPOUNDS Chemical class 0.000 title claims abstract description 206
- 238000002360 preparation method Methods 0.000 title claims abstract description 56
- 238000000034 method Methods 0.000 title claims abstract description 32
- 229930186147 Cephalosporin Natural products 0.000 title abstract description 10
- 229940124587 cephalosporin Drugs 0.000 title abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 175
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 150000002148 esters Chemical class 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 114
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 54
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 50
- 230000002829 reductive effect Effects 0.000 claims description 50
- 239000000460 chlorine Substances 0.000 claims description 43
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- 125000003282 alkyl amino group Chemical group 0.000 claims description 32
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 125000004414 alkyl thio group Chemical group 0.000 claims description 21
- 101150065749 Churc1 gene Proteins 0.000 claims description 19
- 102100038239 Protein Churchill Human genes 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 19
- 125000003277 amino group Chemical group 0.000 claims description 18
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 17
- 125000006239 protecting group Chemical group 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 150000003512 tertiary amines Chemical class 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000000656 azaniumyl group Chemical group [H][N+]([H])([H])[*] 0.000 claims description 9
- 150000001721 carbon Chemical group 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 7
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 7
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 231100000252 nontoxic Toxicity 0.000 claims description 5
- 230000003000 nontoxic effect Effects 0.000 claims description 5
- IKWLIQXIPRUIDU-ZCFIWIBFSA-N (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CCS[C@@H]2CC(=O)N12 IKWLIQXIPRUIDU-ZCFIWIBFSA-N 0.000 claims description 4
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 4
- VVZJLDYMSJTQFD-PQJIZZRHSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-3-[3-(4-carboxypyridin-1-ium-1-yl)prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC=C(C=C2)C(=O)O)C(=O)[O-])C1=O)=NOC VVZJLDYMSJTQFD-PQJIZZRHSA-N 0.000 claims description 3
- BXDLNGMHPBFYMQ-PQJIZZRHSA-N (6R)-3-[3-(3-aminopyridin-1-ium-1-yl)prop-1-enyl]-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC(=CC=C2)N)C(=O)[O-])C1=O)=NOC BXDLNGMHPBFYMQ-PQJIZZRHSA-N 0.000 claims description 2
- KXMHNZHGFXFSFM-JANGERMGSA-N (6R)-3-[3-[3-(aminomethyl)pyridin-1-ium-1-yl]prop-1-enyl]-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC(=CC=C2)CN)C(=O)[O-])C1=O)=NOC KXMHNZHGFXFSFM-JANGERMGSA-N 0.000 claims description 2
- HGRBFSYRGSRKRH-PQJIZZRHSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-3-[3-(1-methylpyrrolidin-1-ium-1-yl)prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2(CCCC2)C)C(=O)[O-])C1=O)=NOC HGRBFSYRGSRKRH-PQJIZZRHSA-N 0.000 claims description 2
- WGDHLPIWSRXXHM-GAGCMDECSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-3-[3-(3-carbamoylpyridin-1-ium-1-yl)prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC(=CC=C2)C(N)=O)C(=O)[O-])C1=O)=NOC WGDHLPIWSRXXHM-GAGCMDECSA-N 0.000 claims description 2
- HJRDTVHCGFPOGR-JANGERMGSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-3-[3-(3-formamidopyridin-1-ium-1-yl)prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC(=CC=C2)NC=O)C(=O)[O-])C1=O)=NOC HJRDTVHCGFPOGR-JANGERMGSA-N 0.000 claims description 2
- KVSLASLCMJYYCU-GAGCMDECSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-3-[3-(4-carbamoylpyridin-1-ium-1-yl)prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC=C(C=C2)C(N)=O)C(=O)[O-])C1=O)=NOC KVSLASLCMJYYCU-GAGCMDECSA-N 0.000 claims description 2
- YUAJZZNGAQXGFF-JANGERMGSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-3-[3-[3-(hydroxymethyl)pyridin-1-ium-1-yl]prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC(=CC=C2)CO)C(=O)[O-])C1=O)=NOC YUAJZZNGAQXGFF-JANGERMGSA-N 0.000 claims description 2
- HNNMEPWLJGGYAP-PQJIZZRHSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-(3-pyridin-1-ium-1-ylprop-1-enyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC=CC=C2)C(=O)[O-])C1=O)=NOC HNNMEPWLJGGYAP-PQJIZZRHSA-N 0.000 claims description 2
- PCPDPVRFZWADPQ-WVQRXBFSSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[3-(trimethylazaniumyl)prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+](C)(C)C)C(=O)[O-])C1=O)=NOC PCPDPVRFZWADPQ-WVQRXBFSSA-N 0.000 claims description 2
- 150000003462 sulfoxides Chemical class 0.000 claims description 2
- NYRAICHKFLANLE-YBMSBYLISA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetyl]amino]-3-[3-(4-carbamoylpyridin-1-ium-1-yl)prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC=C(C=C2)C(N)=O)C(=O)[O-])C1=O)=NOCC NYRAICHKFLANLE-YBMSBYLISA-N 0.000 claims 1
- BBWAAQNGZRAOKF-JANGERMGSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetyl]amino]-3-[3-(4-carboxypyridin-1-ium-1-yl)prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC=C(C=C2)C(=O)O)C(=O)[O-])C1=O)=NOCC BBWAAQNGZRAOKF-JANGERMGSA-N 0.000 claims 1
- RXMCRKYLLLUANK-RGUGMKFQSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-3-[3-(2-methyl-1,3-thiazol-3-ium-3-yl)prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=C(SC=C2)C)C(=O)[O-])C1=O)=NOC RXMCRKYLLLUANK-RGUGMKFQSA-N 0.000 claims 1
- XXSBUYIUZYUKTM-JANGERMGSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-3-[3-[4-(hydroxymethyl)pyridin-1-ium-1-yl]prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC=C(C=C2)CO)C(=O)[O-])C1=O)=NOC XXSBUYIUZYUKTM-JANGERMGSA-N 0.000 claims 1
- UMJVYULJIGQABL-MZVUKIKXSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-prop-2-ynoxyiminoacetyl]amino]-3-[3-(4-carbamoylpyridin-1-ium-1-yl)prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CC[N+]2=CC=C(C=C2)C(N)=O)C(=O)[O-])C1=O)=NOCC#C UMJVYULJIGQABL-MZVUKIKXSA-N 0.000 claims 1
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 1
- 125000001453 quaternary ammonium group Chemical group 0.000 abstract description 10
- 239000003242 anti bacterial agent Substances 0.000 abstract description 5
- 150000004677 hydrates Chemical class 0.000 abstract description 5
- 239000012453 solvate Substances 0.000 abstract description 5
- 150000001412 amines Chemical class 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 190
- 239000000203 mixture Substances 0.000 description 168
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 137
- 239000000243 solution Substances 0.000 description 102
- 238000002844 melting Methods 0.000 description 80
- 230000008018 melting Effects 0.000 description 80
- 238000000354 decomposition reaction Methods 0.000 description 71
- 239000000843 powder Substances 0.000 description 71
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 57
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 48
- 239000002244 precipitate Substances 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 41
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 39
- 238000003756 stirring Methods 0.000 description 39
- 239000000706 filtrate Substances 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
- 239000000047 product Substances 0.000 description 32
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 29
- 235000019253 formic acid Nutrition 0.000 description 29
- 239000008363 phosphate buffer Substances 0.000 description 29
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 26
- 239000000725 suspension Substances 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 21
- 239000012071 phase Substances 0.000 description 21
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 19
- HQKIQQSTJMDYIA-NBXNUCLWSA-N benzhydryl (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl]amino]-3-(3-iodoprop-1-enyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC1=NC(=NS1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)C=CCI)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O)=NOC HQKIQQSTJMDYIA-NBXNUCLWSA-N 0.000 description 19
- 150000007942 carboxylates Chemical class 0.000 description 19
- 239000000543 intermediate Substances 0.000 description 19
- 230000002441 reversible effect Effects 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 17
- 238000004519 manufacturing process Methods 0.000 description 17
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- 238000005406 washing Methods 0.000 description 16
- 239000012141 concentrate Substances 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 238000001704 evaporation Methods 0.000 description 13
- 235000009518 sodium iodide Nutrition 0.000 description 13
- 125000001424 substituent group Chemical group 0.000 description 13
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 10
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 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 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 125000000623 heterocyclic group Chemical group 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000003643 water by type Substances 0.000 description 8
- OSIJZKVBQPTIMT-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetic acid Chemical compound CON=C(C(O)=O)C1=NSC(N)=N1 OSIJZKVBQPTIMT-UHFFFAOYSA-N 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
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- DUBYLCHUVCHBIJ-UHFFFAOYSA-N methyl 2-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,4-thiadiazol-3-yl]-2-prop-2-ynoxyiminoacetate Chemical compound C#CCON=C(C(=O)OC)C1=NSC(NC(=O)OC(C)(C)C)=N1 DUBYLCHUVCHBIJ-UHFFFAOYSA-N 0.000 description 1
- AXHSMHCYVVHTTH-UHFFFAOYSA-N methyl 2-cyclopentyloxyimino-2-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,4-thiadiazol-3-yl]acetate Chemical compound N=1SC(NC(=O)OC(C)(C)C)=NC=1C(C(=O)OC)=NOC1CCCC1 AXHSMHCYVVHTTH-UHFFFAOYSA-N 0.000 description 1
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- CBKFHSNATJJWQK-UHFFFAOYSA-N n-pyridin-3-ylformamide Chemical compound O=CNC1=CC=CN=C1 CBKFHSNATJJWQK-UHFFFAOYSA-N 0.000 description 1
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- 235000005152 nicotinamide Nutrition 0.000 description 1
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- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
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- 239000003960 organic solvent Substances 0.000 description 1
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- 238000007911 parenteral administration Methods 0.000 description 1
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- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 239000012521 purified sample Substances 0.000 description 1
- PTMBWNZJOQBTBK-UHFFFAOYSA-N pyridin-4-ylmethanol Chemical compound OCC1=CC=NC=C1 PTMBWNZJOQBTBK-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
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- 239000012258 stirred mixture Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
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- PHQXGCNECRISKB-UHFFFAOYSA-N tert-butyl n-(pyridin-3-ylmethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=CN=C1 PHQXGCNECRISKB-UHFFFAOYSA-N 0.000 description 1
- NYBWUHOMYZZKOR-UHFFFAOYSA-N tes-adt Chemical class C1=C2C(C#C[Si](CC)(CC)CC)=C(C=C3C(SC=C3)=C3)C3=C(C#C[Si](CC)(CC)CC)C2=CC2=C1SC=C2 NYBWUHOMYZZKOR-UHFFFAOYSA-N 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
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- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/79—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59794184A | 1984-04-09 | 1984-04-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD236735A5 true DD236735A5 (de) | 1986-06-18 |
Family
ID=24393575
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD85274832A DD236735A5 (de) | 1984-04-09 | 1985-04-03 | Verfahren zur herstellung von cephalosporinverbindungen |
| DD85287524A DD249024A5 (de) | 1984-04-09 | 1985-04-03 | Verfahren zur herstellung von cephalosporinverbindungen |
| DD86287525A DD251752A5 (de) | 1984-04-09 | 1986-03-03 | Verfahren zur herstellung von cephalosporinverbindungen |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD85287524A DD249024A5 (de) | 1984-04-09 | 1985-04-03 | Verfahren zur herstellung von cephalosporinverbindungen |
| DD86287525A DD251752A5 (de) | 1984-04-09 | 1986-03-03 | Verfahren zur herstellung von cephalosporinverbindungen |
Country Status (31)
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61145186A (ja) * | 1984-12-20 | 1986-07-02 | Meiji Seika Kaisha Ltd | 新規セフエム化合物及びその製造法 |
| US4708955A (en) * | 1985-06-24 | 1987-11-24 | Bristol-Myers Company | 3-(substituted)propenyl-7-aminothiazol-ylcephalosporanic acids and esters thereof |
| DE3650157T2 (de) * | 1985-12-26 | 1995-05-04 | Eisai Co Ltd | Cephalosporin-verbindungen. |
| AU614723B2 (en) * | 1986-10-13 | 1991-09-12 | Eisai Co. Ltd. | 3-propenylcephem derivative |
| IL84128A (en) * | 1986-10-13 | 1992-12-01 | Eisai Co Ltd | 3-propenylcephem derivatives, their preparation and pharmaceutical compositions containing them |
| JPH085897B2 (ja) * | 1986-11-06 | 1996-01-24 | エーザイ株式会社 | ３−プロペニルセフェム誘導体 |
| FR2622585B1 (fr) * | 1987-11-03 | 1991-04-19 | Roussel Uclaf | Nouvelles cephalosporines comportant en position 3 un radical vinyle substitue, leur procede de preparation, leur application comme medicaments, les compositions les renfermant et les nouveaux intermediaires obtenus |
| ES2013403A6 (es) * | 1988-03-16 | 1990-05-01 | Eisai Co Ltd | Procedimiento para preparar derivados de cefem. |
| JPH0699449B2 (ja) * | 1988-03-16 | 1994-12-07 | エーザイ株式会社 | セフェム誘導体の合成中間体 |
| FR2655042B1 (fr) * | 1989-11-29 | 1994-01-21 | Adir Cie | Nouvelles benzothiazolinones substituees, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| FR2663332B1 (fr) * | 1990-06-15 | 1997-11-07 | Roussel Uclaf | Nouvelles cephalosporines comportant en position 3 un radical propenyle substitue par un ammonium quaternaire, leur procede de preparation, leur application comme medicaments, les compositions les renfermant et les nouveaux intermediaires obtenus. |
| US5126336A (en) * | 1990-08-23 | 1992-06-30 | Bristol-Myers Squibb Company | Antibiotic c-3 catechol-substituted cephalosporin compounds, compositions and method of use thereof |
| AT396108B (de) * | 1991-08-21 | 1993-06-25 | Biochemie Gmbh | Neues verfahren und neue zwischenprodukte zur herstellung von 7-aminocephalosporansaeurederivaten |
| JPH0741484A (ja) * | 1993-07-29 | 1995-02-10 | Katayama Seiyakushiyo:Kk | セフェム化合物及び抗菌剤 |
| US5661144A (en) * | 1994-08-16 | 1997-08-26 | Meiji Seika Kabushiki Kaisha | Cephem derivatives with 3-substituted bis heterocycles |
| AU761450B2 (en) | 1998-06-22 | 2003-06-05 | Basilea Pharmaceutica Ag | Propenyl cephalosporin derivatives |
| EP1666483B1 (en) | 2003-09-09 | 2011-08-17 | Nippon Chemical Industrial Company Limited | Process for producing 3-chloromethyl-3-cephem derivative |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1342241A (en) * | 1970-01-23 | 1974-01-03 | Glaxo Lab Ltd | Cephalosporin compounds |
| US4390534A (en) * | 1978-12-29 | 1983-06-28 | Fujisawa Pharmaceutical Co., Ltd. | Cephem and cepham compounds |
| EP0025017A1 (de) * | 1979-08-28 | 1981-03-11 | Ciba-Geigy Ag | Polyazathiaverbindungen, Verfahren zu ihrer Herstellung, pharmazeutische Präparate enthaltend solche Verbindungen und Verwendung von letzteren |
| US4409214A (en) * | 1979-11-19 | 1983-10-11 | Fujisawa Pharmaceutical, Co., Ltd. | 7-Acylamino-3-vinylcephalosporanic acid derivatives and processes for the preparation thereof |
| GR75644B (enrdf_load_stackoverflow) * | 1980-06-18 | 1984-08-02 | Fujisawa Pharmaceutical Co | |
| GR78245B (enrdf_load_stackoverflow) * | 1980-09-12 | 1984-09-26 | Ciba Geigy Ag | |
| US4521413A (en) * | 1981-09-14 | 1985-06-04 | Fujisawa Pharmaceutical Co., Ltd. | Cephem compounds |
| US4486586A (en) * | 1983-02-10 | 1984-12-04 | Bristol-Myers Company | Cephalosporin derivatives |
-
1985
- 1985-02-14 CA CA000474260A patent/CA1276929C/en not_active Expired - Lifetime
- 1985-03-25 ZA ZA852236A patent/ZA852236B/xx unknown
- 1985-04-02 NZ NZ211659A patent/NZ211659A/xx unknown
- 1985-04-02 AR AR85299945A patent/AR244694A1/es active
- 1985-04-03 DK DK155985A patent/DK155985A/da not_active Application Discontinuation
- 1985-04-03 DD DD85274832A patent/DD236735A5/de unknown
- 1985-04-03 SE SE8501680A patent/SE466205B/sv not_active IP Right Cessation
- 1985-04-03 DD DD85287524A patent/DD249024A5/de unknown
- 1985-04-03 DE DE19853512225 patent/DE3512225A1/de active Granted
- 1985-04-04 PT PT80246A patent/PT80246B/pt unknown
- 1985-04-04 CH CH1498/85A patent/CH669197A5/de not_active IP Right Cessation
- 1985-04-04 FI FI851379A patent/FI84830C/fi not_active IP Right Cessation
- 1985-04-04 GB GB08508846A patent/GB2157293B/en not_active Expired
- 1985-04-04 NL NL8501002A patent/NL192925C/nl not_active IP Right Cessation
- 1985-04-04 OA OA58561A patent/OA07985A/xx unknown
- 1985-04-04 AU AU40862/85A patent/AU580990B2/en not_active Expired
- 1985-04-04 IE IE86685A patent/IE58408B1/en not_active IP Right Cessation
- 1985-04-05 IT IT20267/85A patent/IT1190353B/it active
- 1985-04-05 LU LU85840A patent/LU85840A1/fr unknown
- 1985-04-05 AT AT0103985A patent/AT388735B/de not_active IP Right Cessation
- 1985-04-05 FR FR8505281A patent/FR2563832B1/fr not_active Expired
- 1985-04-05 IL IL74826A patent/IL74826A/xx not_active IP Right Cessation
- 1985-04-08 GR GR850883A patent/GR850883B/el not_active IP Right Cessation
- 1985-04-08 ES ES542013A patent/ES8607318A1/es not_active Expired
- 1985-04-08 RU SU853878102A patent/RU2056425C1/ru active
- 1985-04-09 BE BE0/214810A patent/BE902148A/fr not_active IP Right Cessation
- 1985-04-09 HU HU851299A patent/HU193750B/hu unknown
- 1985-04-09 JP JP60075233A patent/JPS615084A/ja active Granted
- 1985-04-09 YU YU60085A patent/YU46151B/sh unknown
- 1985-04-09 KR KR1019850002383A patent/KR870002166B1/ko not_active Expired
- 1985-04-09 HU HU87151A patent/HU204277B/hu unknown
- 1985-11-12 JP JP60252138A patent/JPS61143390A/ja active Granted
- 1985-11-12 JP JP60252140A patent/JPS61143387A/ja active Granted
- 1985-11-12 JP JP60252139A patent/JPS61143391A/ja active Granted
-
1986
- 1986-01-31 ES ES551551A patent/ES8706694A1/es not_active Expired
- 1986-01-31 ES ES551550A patent/ES8706155A1/es not_active Expired
- 1986-02-06 SU SU864019975A patent/SU1487814A3/ru active
- 1986-02-06 SU SU864023036A patent/SU1367858A3/ru active
- 1986-02-06 SU SU864020682A patent/SU1436882A3/ru active
- 1986-02-06 SU SU864018257A patent/SU1375140A3/ru active
- 1986-03-03 DD DD86287525A patent/DD251752A5/de unknown
- 1986-09-10 ES ES557060A patent/ES8800949A1/es not_active Expired
-
1987
- 1987-06-25 YU YU118987A patent/YU46213B/sh unknown
- 1987-09-10 GB GB08721347A patent/GB2194790B/en not_active Expired
- 1987-09-10 GB GB08721346A patent/GB2194789B/en not_active Expired
- 1987-10-01 MY MYPI87002761A patent/MY101940A/en unknown
-
1988
- 1988-11-11 AU AU25041/88A patent/AU610278B2/en not_active Expired
-
1989
- 1989-04-04 IE IE121089A patent/IE58403B1/en not_active IP Right Cessation
- 1989-04-06 SE SE8901224A patent/SE470259B/sv not_active IP Right Cessation
- 1989-04-06 SE SE8901225A patent/SE505256C2/sv not_active IP Right Cessation
- 1989-04-06 SE SE8901226A patent/SE470260B/sv not_active IP Right Cessation
-
1991
- 1991-08-12 CA CA000616143A patent/CA1340638C/en not_active Expired - Fee Related
- 1991-08-21 CA CA000616144A patent/CA1340672C/en not_active Expired - Fee Related
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| IF04 | In force in the year 2004 |
Expiry date: 20050404 |