AT392471B - Verfahren zur herstellung von neuen 7beta-(2-(2- amino-4-thiazolyl)-alkenoylamino)-3-cephem-4- carbonsaeureestern - Google Patents
Verfahren zur herstellung von neuen 7beta-(2-(2- amino-4-thiazolyl)-alkenoylamino)-3-cephem-4- carbonsaeureestern Download PDFInfo
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- AT392471B AT392471B AT823/86A AT82386A AT392471B AT 392471 B AT392471 B AT 392471B AT 823/86 A AT823/86 A AT 823/86A AT 82386 A AT82386 A AT 82386A AT 392471 B AT392471 B AT 392471B
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- -1 2- AMINO-4-THIAZOLYL Chemical class 0.000 title claims description 117
- 238000004519 manufacturing process Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 58
- 239000002253 acid Substances 0.000 claims description 28
- 150000002148 esters Chemical class 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000004185 ester group Chemical group 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 239000002841 Lewis acid Substances 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 3
- RJFPBECTFIUTHB-INEUFUBQSA-N (6r,7r)-7-azaniumyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S1CC=C(C(O)=O)N2C(=O)[C@@H](N)[C@H]21 RJFPBECTFIUTHB-INEUFUBQSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000005767 propoxymethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])[#8]C([H])([H])* 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 150000003462 sulfoxides Chemical class 0.000 description 9
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000002252 acyl group Chemical group 0.000 description 6
- 239000003242 anti bacterial agent Substances 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000000370 acceptor Substances 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 150000008064 anhydrides Chemical class 0.000 description 5
- 229940088710 antibiotic agent Drugs 0.000 description 5
- 229910002091 carbon monoxide Inorganic materials 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 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 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- 239000011707 mineral Substances 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229930186147 Cephalosporin Natural products 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 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 3
- 229960003022 amoxicillin Drugs 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 229940124587 cephalosporin Drugs 0.000 description 3
- 150000001780 cephalosporins Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000013256 coordination polymer Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000002024 ethyl acetate extract Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 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 3
- 239000003208 petroleum Substances 0.000 description 3
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical class ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 125000004665 trialkylsilyl group Chemical group 0.000 description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- XIXNSLABECPEMI-UHFFFAOYSA-N 2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]pent-2-enoic acid Chemical compound CCC=C(C(O)=O)C1=CSC(NC(=O)OC(C)(C)C)=N1 XIXNSLABECPEMI-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- 102100022749 Aminopeptidase N Human genes 0.000 description 2
- 101710099461 Aminopeptidase N Proteins 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N CD3OD Substances [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 239000002262 Schiff base Substances 0.000 description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000003463 adsorbent Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000001118 alkylidene group Chemical group 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 150000004965 peroxy acids Chemical class 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
- 125000006000 trichloroethyl group Chemical group 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- 150000003952 β-lactams Chemical class 0.000 description 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 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
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- 125000000101 thioether group Chemical group 0.000 description 1
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- 150000003573 thiols Chemical class 0.000 description 1
- IUTCEZPPWBHGIX-UHFFFAOYSA-N tin(2+) Chemical class [Sn+2] IUTCEZPPWBHGIX-UHFFFAOYSA-N 0.000 description 1
- XJLBFCVPIIFHQU-UHFFFAOYSA-N triazine;trihydrochloride Chemical compound Cl.Cl.Cl.C1=CN=NN=C1 XJLBFCVPIIFHQU-UHFFFAOYSA-N 0.000 description 1
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- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
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- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 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
- 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
-
- 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)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT0159089A AT397963B (de) | 1985-03-29 | 1989-06-28 | Verfahren zur herstellung von neuen 7 beta-(2-(2- amino-4-thiazolyl)-alkenoylamimo)-3-cephem-4- carbonsäureestern |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6728085 | 1985-03-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ATA82386A ATA82386A (de) | 1990-09-15 |
| AT392471B true AT392471B (de) | 1991-04-10 |
Family
ID=13340398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT823/86A AT392471B (de) | 1985-03-29 | 1986-03-27 | Verfahren zur herstellung von neuen 7beta-(2-(2- amino-4-thiazolyl)-alkenoylamino)-3-cephem-4- carbonsaeureestern |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4731361A (en:Method) |
| JP (1) | JPS6289A (en:Method) |
| KR (1) | KR870001983B1 (en:Method) |
| AT (1) | AT392471B (en:Method) |
| AU (1) | AU580855B2 (en:Method) |
| BE (1) | BE904517A (en:Method) |
| BR (1) | BR1100475A (en:Method) |
| CA (1) | CA1269655A (en:Method) |
| CH (1) | CH669600A5 (en:Method) |
| DE (1) | DE3610581A1 (en:Method) |
| ES (2) | ES8800237A1 (en:Method) |
| FR (1) | FR2579597B1 (en:Method) |
| GB (1) | GB2173194B (en:Method) |
| GR (1) | GR860838B (en:Method) |
| HK (1) | HK47993A (en:Method) |
| IL (1) | IL78301A (en:Method) |
| IT (1) | IT1191997B (en:Method) |
| NL (1) | NL192926C (en:Method) |
| SU (3) | SU1581223A3 (en:Method) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ220764A (en) * | 1986-07-02 | 1989-09-27 | Shionogi & Co | Crystalline form of 7beta((z)-2-(2-aminothiazol-4-yl)-4- carboxybut-2-enoylamino)-3-cephem-4-carboxylic acid and pharmaceutical compositions |
| US5017380A (en) * | 1986-07-02 | 1991-05-21 | Shionogi & Co., Ltd. | Gelatin hard capsule containing crystalline hydrate of oral cephalosporin |
| US5242913A (en) * | 1987-03-11 | 1993-09-07 | Pfizer Inc. | Substituted 3-cephem compounds as antibacterial agents |
| IL89836A0 (en) * | 1988-04-06 | 1989-12-15 | Beecham Group Plc | Penicilanic acid derivatives,process for their preparation and pharmaceutical compositions containing them |
| US5245027A (en) * | 1989-11-21 | 1993-09-14 | Bristol-Myers Squibb Company | 3-fluorosulfonyloxyceph-3-em compounds |
| TW203552B (en) * | 1992-02-18 | 1993-04-11 | J Baroody Lloyd | Compositions of clindamycin and benzoyl peroxide for acne treatment |
| JP2002356427A (ja) * | 2001-05-30 | 2002-12-13 | Shionogi & Co Ltd | β−ラクタマーゼ阻害剤 |
| AR036053A1 (es) * | 2001-06-15 | 2004-08-04 | Versicor Inc | Compuestos de n-formil-hidroxilamina, un proceso para su preparacion y composiciones farmaceuticas |
| TWI364282B (en) * | 2005-01-31 | 2012-05-21 | Shionogi & Co | Cefcapene pivoxil methanesulfonic acid salt |
| WO2008155615A2 (en) * | 2007-06-18 | 2008-12-24 | Orchid Chemicals & Pharmaceuticals Limited | An improved process for the preparation of cephalosporin antibiotic |
| CN101747344B (zh) * | 2009-12-22 | 2012-07-04 | 山东润泽制药有限公司 | 盐酸头孢卡品酯的合成方法 |
| CN103087080B (zh) * | 2011-11-03 | 2016-08-31 | 石药集团中奇制药技术（石家庄）有限公司 | 一种盐酸头孢卡品酯的制备方法及其合成中间体 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2710282A1 (de) * | 1976-03-09 | 1977-09-15 | Fujisawa Pharmaceutical Co | 3,7-disubstituierte-3-cephem-4- carbonsaeureverbindungen, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische mittel |
| DE3111159A1 (de) * | 1980-04-14 | 1982-02-25 | Farmitalia Carlo Erba S.p.A., 20159 Milano | (alpha),ss-disubstituierte acrylamidocephalosporine, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische und veterinaermedizinische mittel |
| EP0049448A2 (de) * | 1980-10-08 | 1982-04-14 | Bayer Ag | Beta-Lactamantibiotika, Verfahren zu deren Herstellung sowie sie enthaltende Mittel |
| EP0107138A2 (de) * | 1982-10-23 | 1984-05-02 | Bayer Ag | Neue Cephalosporine und Verfahren zu ihrer Herstellung |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2715385A1 (de) * | 1976-04-14 | 1977-11-10 | Takeda Chemical Industries Ltd | Cephalosporinderivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittel |
| DE3145727A1 (de) * | 1981-11-19 | 1983-05-26 | Bayer Ag, 5090 Leverkusen | Zwischenprodukte, verfahren zu deren herstellung und verfahren zur herstellung von cephalosporinen |
| CA1201431A (en) * | 1981-12-17 | 1986-03-04 | Daiei Tunemoto | .beta.-LACTAM COMPOUNDS, PROCESS FOR THE PREPARATION THEREOF AND INTERMEDIATE PRODUCTS FOR THE PREPARATION THEREOF |
| JPS5984890A (ja) * | 1982-11-05 | 1984-05-16 | Hisayasu Ishimaru | 経口用セフアロスポリン化合物 |
| DE3300593A1 (de) * | 1983-01-11 | 1984-07-12 | Bayer Ag, 5090 Leverkusen | Neue cephalosporine und verfahren zu ihrer herstellung |
| JPS6051193A (ja) * | 1983-08-31 | 1985-03-22 | Kyoto Yakuhin Kogyo Kk | セフェム系化合物 |
| AU575854B2 (en) * | 1983-10-04 | 1988-08-11 | Shionogi & Co., Ltd. | 7beta-(carboxyalkenamido) cephalosporins |
| DE3343208A1 (de) * | 1983-11-30 | 1985-06-05 | Bayer Ag, 5090 Leverkusen | Neue cephalosporine und verfahren zu ihrer herstellung |
| DE3419012A1 (de) * | 1984-05-22 | 1985-11-28 | Bayer Ag, 5090 Leverkusen | Ss-lactamantibiotika, verfahren zu deren herstellung sowie ihre verwendung als arzneimittel oder wachstumsfoerderer in der tieraufzucht oder als antioxidantien |
| EP0187456A1 (en) * | 1984-11-29 | 1986-07-16 | Ici Pharma | Cephalosporin derivatives |
-
1986
- 1986-03-25 AU AU55204/86A patent/AU580855B2/en not_active Expired
- 1986-03-26 ES ES553426A patent/ES8800237A1/es not_active Expired
- 1986-03-26 CH CH1219/86A patent/CH669600A5/de not_active IP Right Cessation
- 1986-03-27 DE DE19863610581 patent/DE3610581A1/de active Granted
- 1986-03-27 AT AT823/86A patent/AT392471B/de not_active IP Right Cessation
- 1986-03-27 CA CA000505441A patent/CA1269655A/en not_active Expired - Lifetime
- 1986-03-27 NL NL8600804A patent/NL192926C/nl not_active IP Right Cessation
- 1986-03-27 US US06/845,305 patent/US4731361A/en not_active Expired - Lifetime
- 1986-03-27 JP JP61070461A patent/JPS6289A/ja active Granted
- 1986-03-27 FR FR868604446A patent/FR2579597B1/fr not_active Expired - Lifetime
- 1986-03-27 GB GB8607855A patent/GB2173194B/en not_active Expired
- 1986-03-28 SU SU864027240A patent/SU1581223A3/ru active
- 1986-03-28 BE BE0/216476A patent/BE904517A/fr not_active IP Right Cessation
- 1986-03-28 GR GR860838A patent/GR860838B/el unknown
- 1986-03-28 IL IL78301A patent/IL78301A/xx unknown
- 1986-03-28 IT IT67257/86A patent/IT1191997B/it active
- 1986-03-29 KR KR1019860002387A patent/KR870001983B1/ko not_active Expired
-
1987
- 1987-07-31 ES ES557640A patent/ES8801922A1/es not_active Expired
- 1987-08-26 SU SU874203179A patent/SU1575941A3/ru active
- 1987-09-08 SU SU874203251A patent/SU1556541A3/ru active
-
1993
- 1993-05-20 HK HK479/93A patent/HK47993A/xx not_active IP Right Cessation
-
1997
- 1997-05-05 BR BR1100475-4A patent/BR1100475A/pt active IP Right Grant
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2710282A1 (de) * | 1976-03-09 | 1977-09-15 | Fujisawa Pharmaceutical Co | 3,7-disubstituierte-3-cephem-4- carbonsaeureverbindungen, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische mittel |
| DE3111159A1 (de) * | 1980-04-14 | 1982-02-25 | Farmitalia Carlo Erba S.p.A., 20159 Milano | (alpha),ss-disubstituierte acrylamidocephalosporine, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische und veterinaermedizinische mittel |
| EP0049448A2 (de) * | 1980-10-08 | 1982-04-14 | Bayer Ag | Beta-Lactamantibiotika, Verfahren zu deren Herstellung sowie sie enthaltende Mittel |
| EP0107138A2 (de) * | 1982-10-23 | 1984-05-02 | Bayer Ag | Neue Cephalosporine und Verfahren zu ihrer Herstellung |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ELA | Expired due to lapse of time |