CA1171405A - Cephalosporine desacetoxy esters, salts thereof and processes for preparing the same - Google Patents
Cephalosporine desacetoxy esters, salts thereof and processes for preparing the sameInfo
- Publication number
- CA1171405A CA1171405A CA000372576A CA372576A CA1171405A CA 1171405 A CA1171405 A CA 1171405A CA 000372576 A CA000372576 A CA 000372576A CA 372576 A CA372576 A CA 372576A CA 1171405 A CA1171405 A CA 1171405A
- Authority
- CA
- Canada
- Prior art keywords
- ester
- chlorohydrate
- adca
- acid
- phtalidic
- Prior art date
- 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
Links
- 150000002148 esters Chemical class 0.000 title claims abstract description 97
- 150000003839 salts Chemical class 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims description 37
- HOKIDJSKDBPKTQ-UHFFFAOYSA-N 3-(acetyloxymethyl)-7-[(5-amino-5-carboxypentanoyl)amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C(NC(=O)CCCC(N)C(O)=O)C12 HOKIDJSKDBPKTQ-UHFFFAOYSA-N 0.000 title abstract 2
- NVIAYEIXYQCDAN-CLZZGJSISA-N 7beta-aminodeacetoxycephalosporanic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](N)[C@@H]12 NVIAYEIXYQCDAN-CLZZGJSISA-N 0.000 claims abstract description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000002904 solvent Substances 0.000 claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- 238000005406 washing Methods 0.000 claims abstract description 16
- NMKSBNZBSLHAKW-UHFFFAOYSA-N Cl.ClO Chemical compound Cl.ClO NMKSBNZBSLHAKW-UHFFFAOYSA-N 0.000 claims abstract description 15
- 230000002378 acidificating effect Effects 0.000 claims abstract description 15
- LJCWONGJFPCTTL-SSDOTTSWSA-N D-4-hydroxyphenylglycine Chemical compound [O-]C(=O)[C@H]([NH3+])C1=CC=C(O)C=C1 LJCWONGJFPCTTL-SSDOTTSWSA-N 0.000 claims abstract description 9
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 claims abstract description 9
- ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 8
- 150000003973 alkyl amines Chemical class 0.000 claims abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 70
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 66
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 50
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 42
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 30
- 229960002588 cefradine Drugs 0.000 claims description 26
- RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 claims description 26
- 229950006327 napsilate Drugs 0.000 claims description 25
- 229950004288 tosilate Drugs 0.000 claims description 23
- 239000003208 petroleum Substances 0.000 claims description 21
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 16
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 14
- 239000003495 polar organic solvent Substances 0.000 claims description 14
- 239000011541 reaction mixture Substances 0.000 claims description 14
- 239000012453 solvate Substances 0.000 claims description 8
- 150000004682 monohydrates Chemical class 0.000 claims description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 4
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 claims description 4
- 159000000000 sodium salts Chemical class 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 125000001271 cephalosporin group Chemical group 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 15
- 238000002360 preparation method Methods 0.000 claims 12
- 229940086542 triethylamine Drugs 0.000 claims 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 2
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 claims 2
- -1 sodium sulfonate monohydrate Chemical class 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000003115 biocidal effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000012071 phase Substances 0.000 description 22
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 18
- 239000000047 product Substances 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 230000002906 microbiologic effect Effects 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 239000005457 ice water Substances 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-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
- 239000007832 Na2SO4 Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 229940113088 dimethylacetamide Drugs 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000000370 acceptor Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 2
- 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 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229960004841 cefadroxil Drugs 0.000 description 1
- NBFNMSULHIODTC-CYJZLJNKSA-N cefadroxil monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=C(O)C=C1 NBFNMSULHIODTC-CYJZLJNKSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- KINULKKPVJYRON-PVNXHVEDSA-N n-[(e)-[10-[(e)-(4,5-dihydro-1h-imidazol-2-ylhydrazinylidene)methyl]anthracen-9-yl]methylideneamino]-4,5-dihydro-1h-imidazol-2-amine;hydron;dichloride Chemical compound Cl.Cl.N1CCN=C1N\N=C\C(C1=CC=CC=C11)=C(C=CC=C2)C2=C1\C=N\NC1=NCCN1 KINULKKPVJYRON-PVNXHVEDSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 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
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/22—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with radicals containing only hydrogen and carbon atoms, attached in position 3
-
- 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
Landscapes
- 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT21463/80A IT1141286B (it) | 1980-04-17 | 1980-04-17 | Esteri delle desacetossi cefalosporine loro sali e procedimenti per il loro ottenimento |
| IT21463A/80 | 1980-04-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1171405A true CA1171405A (en) | 1984-07-24 |
Family
ID=11182169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000372576A Expired CA1171405A (en) | 1980-04-17 | 1981-03-09 | Cephalosporine desacetoxy esters, salts thereof and processes for preparing the same |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4388460A (cg-RX-API-DMAC7.html) |
| JP (1) | JPS56147789A (cg-RX-API-DMAC7.html) |
| CA (1) | CA1171405A (cg-RX-API-DMAC7.html) |
| CH (1) | CH652406A5 (cg-RX-API-DMAC7.html) |
| DE (1) | DE3115244A1 (cg-RX-API-DMAC7.html) |
| FR (1) | FR2480753A1 (cg-RX-API-DMAC7.html) |
| GB (1) | GB2074157B (cg-RX-API-DMAC7.html) |
| IL (1) | IL62376A (cg-RX-API-DMAC7.html) |
| IT (1) | IT1141286B (cg-RX-API-DMAC7.html) |
| NL (1) | NL8101482A (cg-RX-API-DMAC7.html) |
| YU (1) | YU101681A (cg-RX-API-DMAC7.html) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0562527A (ja) * | 1991-09-04 | 1993-03-12 | Sanyo Kogyo Kk | 平形配線ケーブル |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3485812A (en) * | 1966-08-30 | 1969-12-23 | Gulf Research Development Co | Processes for preparing ethylene polymers |
| GB1355804A (en) * | 1970-12-04 | 1974-06-05 | Beecham Group Ltd | Penicillins and cephalosporinesters |
| US3985741A (en) * | 1972-09-15 | 1976-10-12 | Bristol-Myers Company | Production of p-hydroxycephalexin |
| US4092476A (en) * | 1974-02-21 | 1978-05-30 | Beecham Group Limited | Phthalidyl esters of 7-[(α amino, 2 substituted acetamido)-3-(heterocyclic-thio methyl)]cephalosporins |
| GB1492393A (en) * | 1974-02-21 | 1977-11-16 | Beecham Group Ltd | Cephalosporin esters |
| JPS597717B2 (ja) * | 1976-09-08 | 1984-02-20 | 武田薬品工業株式会社 | セフアロスポリン誘導体およびその製造法 |
| CH634848A5 (de) * | 1976-08-17 | 1983-02-28 | Fujisawa Pharmaceutical Co | Verfahren zur herstellung neuer 7-(n-substituierter 2-phenylglycinamido)-3-substituierte-3-cephem-4-carbonsaeuren. |
| JPS6011713B2 (ja) * | 1976-09-08 | 1985-03-27 | 武田薬品工業株式会社 | セフアロスポリン誘導体およびその製造法 |
| DE2716677C2 (de) * | 1977-04-15 | 1985-10-10 | Hoechst Ag, 6230 Frankfurt | Cephemderivate und Verfahren zu ihrer Herstellung |
-
1980
- 1980-04-17 IT IT21463/80A patent/IT1141286B/it active
-
1981
- 1981-03-04 US US06/240,309 patent/US4388460A/en not_active Expired - Lifetime
- 1981-03-09 CA CA000372576A patent/CA1171405A/en not_active Expired
- 1981-03-16 IL IL62376A patent/IL62376A/xx unknown
- 1981-03-16 JP JP3666981A patent/JPS56147789A/ja active Granted
- 1981-03-24 CH CH1982/81A patent/CH652406A5/it not_active IP Right Cessation
- 1981-03-25 NL NL8101482A patent/NL8101482A/xx not_active Application Discontinuation
- 1981-03-31 GB GB8109979A patent/GB2074157B/en not_active Expired
- 1981-04-07 FR FR8106971A patent/FR2480753A1/fr active Granted
- 1981-04-15 DE DE19813115244 patent/DE3115244A1/de not_active Ceased
- 1981-04-17 YU YU01016/81A patent/YU101681A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IT8021463A0 (it) | 1980-04-17 |
| GB2074157B (en) | 1984-02-29 |
| FR2480753B1 (cg-RX-API-DMAC7.html) | 1984-12-14 |
| US4388460A (en) | 1983-06-14 |
| IL62376A (en) | 1984-07-31 |
| NL8101482A (nl) | 1981-11-16 |
| JPH0250916B2 (cg-RX-API-DMAC7.html) | 1990-11-05 |
| JPS56147789A (en) | 1981-11-16 |
| GB2074157A (en) | 1981-10-28 |
| FR2480753A1 (fr) | 1981-10-23 |
| YU101681A (en) | 1983-12-31 |
| DE3115244A1 (de) | 1982-05-13 |
| IT1141286B (it) | 1986-10-01 |
| CH652406A5 (it) | 1985-11-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |