IE41799B1 - Process for preparing 3-methyl-4-(5-tetrazolyl)- 3-cephem compounds - Google Patents
Process for preparing 3-methyl-4-(5-tetrazolyl)- 3-cephem compoundsInfo
- Publication number
- IE41799B1 IE41799B1 IE2059/75A IE205975A IE41799B1 IE 41799 B1 IE41799 B1 IE 41799B1 IE 2059/75 A IE2059/75 A IE 2059/75A IE 205975 A IE205975 A IE 205975A IE 41799 B1 IE41799 B1 IE 41799B1
- Authority
- IE
- Ireland
- Prior art keywords
- penam
- tetrazolyl
- acid
- ppm
- dimethyl
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- -1 3-methyl-4-(5-tetrazolyl)- 3-cephem compounds Chemical class 0.000 title abstract description 82
- 238000006243 chemical reaction Methods 0.000 claims abstract description 55
- 239000002253 acid Substances 0.000 claims abstract description 42
- 239000007788 liquid Substances 0.000 claims abstract description 25
- 238000010438 heat treatment Methods 0.000 claims abstract description 7
- 150000003860 tertiary carboxamides Chemical class 0.000 claims abstract description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 47
- 230000008569 process Effects 0.000 claims description 28
- 239000000203 mixture Chemical group 0.000 claims description 23
- 239000000126 substance Substances 0.000 claims description 11
- ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 8
- INAVQIOTUQGEAF-LWOQYNTDSA-N C([C@H]1SC2(C)C)C(=O)N1C2C1=NN=NN1 Chemical compound C([C@H]1SC2(C)C)C(=O)N1C2C1=NN=NN1 INAVQIOTUQGEAF-LWOQYNTDSA-N 0.000 claims description 3
- 229940124530 sulfonamide Drugs 0.000 claims description 2
- 125000000565 sulfonamide group Chemical group 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 23
- 239000003242 anti bacterial agent Substances 0.000 abstract description 15
- 239000000543 intermediate Substances 0.000 abstract description 7
- 239000000376 reactant Substances 0.000 abstract description 7
- 150000003462 sulfoxides Chemical class 0.000 abstract description 4
- CMPVUVUNJQERIT-UHFFFAOYSA-N tertiary sulfonamide Chemical group CC(C)CC1=NC=CS1 CMPVUVUNJQERIT-UHFFFAOYSA-N 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 124
- 239000000243 solution Substances 0.000 description 77
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- 150000001875 compounds Chemical class 0.000 description 46
- 239000000047 product Substances 0.000 description 38
- 239000002904 solvent Substances 0.000 description 32
- 239000001257 hydrogen Substances 0.000 description 30
- 229910052739 hydrogen Inorganic materials 0.000 description 30
- 238000003756 stirring Methods 0.000 description 30
- 125000004432 carbon atom Chemical group C* 0.000 description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
- 125000003831 tetrazolyl group Chemical group 0.000 description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 23
- WSHJJCPTKWSMRR-RXMQYKEDSA-N penam Chemical compound S1CCN2C(=O)C[C@H]21 WSHJJCPTKWSMRR-RXMQYKEDSA-N 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 125000006239 protecting group Chemical group 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 230000009102 absorption Effects 0.000 description 16
- 238000010521 absorption reaction Methods 0.000 description 16
- 125000002252 acyl group Chemical group 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 15
- 230000008020 evaporation Effects 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 125000000217 alkyl group Chemical group 0.000 description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 11
- 150000001408 amides Chemical class 0.000 description 11
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 10
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 239000002243 precursor Substances 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000012429 reaction media Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 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 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 125000005042 acyloxymethyl group Chemical group 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 125000002541 furyl group Chemical group 0.000 description 7
- 238000002329 infrared spectrum Methods 0.000 description 7
- 125000005633 phthalidyl group Chemical group 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 150000003536 tetrazoles Chemical class 0.000 description 7
- 125000001544 thienyl group Chemical group 0.000 description 7
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 description 6
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000003463 adsorbent Substances 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 150000008064 anhydrides Chemical class 0.000 description 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
- 150000001782 cephems Chemical class 0.000 description 6
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 6
- 229940093499 ethyl acetate Drugs 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000002002 slurry Substances 0.000 description 6
- 150000003952 β-lactams Chemical group 0.000 description 6
- ZMMRLWFGWQVVJD-UHFFFAOYSA-O (n,n-dimethylcarbamimidoyl)-dimethylazanium;azide Chemical compound [N-]=[N+]=[N-].CN(C)C(N)=[N+](C)C ZMMRLWFGWQVVJD-UHFFFAOYSA-O 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- 229930182555 Penicillin Natural products 0.000 description 5
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 5
- 239000003377 acid catalyst Substances 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
- 125000003460 beta-lactamyl group Chemical group 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- LLHRMWHYJGLIEV-UHFFFAOYSA-N desoxy Chemical group COC1=CC(CCN)=CC(OC)=C1C LLHRMWHYJGLIEV-UHFFFAOYSA-N 0.000 description 5
- JSYGRUBHOCKMGQ-UHFFFAOYSA-N dichloramine Chemical compound ClNCl JSYGRUBHOCKMGQ-UHFFFAOYSA-N 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 5
- 150000002959 penams Chemical class 0.000 description 5
- 229940049954 penicillin Drugs 0.000 description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 5
- 235000011007 phosphoric acid Nutrition 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 150000003512 tertiary amines Chemical class 0.000 description 5
- AWRSDQGCXNOXOC-NUWLTMBBSA-N (5r)-6-amino-3,3-dimethyl-2-(2h-tetrazol-5-yl)-4-thia-1-azabicyclo[3.2.0]heptan-7-one Chemical compound NC([C@H]1SC2(C)C)C(=O)N1C2C=1N=NNN=1 AWRSDQGCXNOXOC-NUWLTMBBSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical compound [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 125000001786 isothiazolyl group Chemical group 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 4
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 4
- 125000003226 pyrazolyl group Chemical group 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 125000000335 thiazolyl group Chemical group 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 125000001425 triazolyl group Chemical group 0.000 description 4
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical class C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- BEHCKFJXZNGVDV-QEMNHKJVSA-N (5r)-2-[1-(furan-2-ylmethyl)tetrazol-5-yl]-3,3-dimethyl-6-(tritylamino)-4-thia-1-azabicyclo[3.2.0]heptan-7-one Chemical compound C1([C@H]2SC(C(N2C1=O)C=1N(N=NN=1)CC=1OC=CC=1)(C)C)NC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 BEHCKFJXZNGVDV-QEMNHKJVSA-N 0.000 description 3
- UAERYXLDIHQAMK-ARDYHYPTSA-N (5r)-n-[(4-hydroxyphenyl)methyl]-3,3-dimethyl-7-oxo-6-(tritylamino)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxamide Chemical compound C1([C@H]2SC(C(N2C1=O)C(=O)NCC=1C=CC(O)=CC=1)(C)C)NC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UAERYXLDIHQAMK-ARDYHYPTSA-N 0.000 description 3
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 239000012445 acidic reagent Substances 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- DDRPCXLAQZKBJP-UHFFFAOYSA-N furfurylamine Chemical compound NCC1=CC=CO1 DDRPCXLAQZKBJP-UHFFFAOYSA-N 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- KMYKMCGJWDBRSV-KOHJWAIASA-N n-[(5r)-3,3-dimethyl-7-oxo-2-(2h-tetrazol-5-yl)-4-thia-1-azabicyclo[3.2.0]heptan-6-yl]-2-phenylacetamide Chemical compound C1([C@H]2SC(C(N2C1=O)C1=NNN=N1)(C)C)NC(=O)CC1=CC=CC=C1 KMYKMCGJWDBRSV-KOHJWAIASA-N 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 150000003013 phosphoric acid derivatives Chemical group 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
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- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 2
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- 125000005843 halogen group Chemical group 0.000 description 1
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- JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 description 1
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- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 1
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- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- VPCDQGACGWYTMC-UHFFFAOYSA-N nitrosyl chloride Chemical compound ClN=O VPCDQGACGWYTMC-UHFFFAOYSA-N 0.000 description 1
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- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- MHYFEEDKONKGEB-UHFFFAOYSA-N oxathiane 2,2-dioxide Chemical compound O=S1(=O)CCCCO1 MHYFEEDKONKGEB-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
- HFNGWVXNSWWIGC-UHFFFAOYSA-N phenylmethoxy carbonochloridate Chemical compound ClC(=O)OOCC1=CC=CC=C1 HFNGWVXNSWWIGC-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- AAZYNPCMLRQUHI-UHFFFAOYSA-N propan-2-one;2-propan-2-yloxypropane Chemical compound CC(C)=O.CC(C)OC(C)C AAZYNPCMLRQUHI-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- ZSDGGBCKZCKOLL-UHFFFAOYSA-O pyridin-1-ium;azide Chemical compound [N-]=[N+]=[N-].C1=CC=[NH+]C=C1 ZSDGGBCKZCKOLL-UHFFFAOYSA-O 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 150000008053 sultones Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- VKDYDXILKHBYHT-UHFFFAOYSA-O tributylazanium;azide Chemical compound [N-]=[N+]=[N-].CCCC[NH+](CCCC)CCCC VKDYDXILKHBYHT-UHFFFAOYSA-O 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical class C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52144474A | 1974-11-06 | 1974-11-06 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE41799L IE41799L (en) | 1976-05-06 |
| IE41799B1 true IE41799B1 (en) | 1980-03-26 |
Family
ID=24076758
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2059/75A IE41799B1 (en) | 1974-11-06 | 1975-09-19 | Process for preparing 3-methyl-4-(5-tetrazolyl)- 3-cephem compounds |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS5170790A (https=) |
| BE (1) | BE835299A (https=) |
| CA (1) | CA1050010A (https=) |
| DE (1) | DE2546503A1 (https=) |
| DK (1) | DK496975A (https=) |
| ES (2) | ES442360A1 (https=) |
| FR (1) | FR2290445A1 (https=) |
| GB (2) | GB1520479A (https=) |
| IE (1) | IE41799B1 (https=) |
| LU (1) | LU73730A1 (https=) |
| NL (1) | NL7512960A (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4845088A (en) * | 1985-07-01 | 1989-07-04 | Merck & Co., Inc. | Tetrazolyl derivatives of beta-lactams useful as elastase inhibitors |
| US4699904A (en) * | 1985-07-01 | 1987-10-13 | Merck & Co., Inc. | Tetrazolyl derivatives of β-lactams useful as elastase inhibitors |
| US9334289B2 (en) | 2011-04-28 | 2016-05-10 | Shionogi & Co., Ltd. | Cephem compound having catechol or pseudo-catechol structure |
-
1975
- 1975-09-19 IE IE2059/75A patent/IE41799B1/en unknown
- 1975-10-17 DE DE19752546503 patent/DE2546503A1/de active Pending
- 1975-10-28 CA CA238,486A patent/CA1050010A/en not_active Expired
- 1975-10-31 GB GB45549/75A patent/GB1520479A/en not_active Expired
- 1975-10-31 GB GB52782/77A patent/GB1520480A/en not_active Expired
- 1975-11-04 JP JP50132413A patent/JPS5170790A/ja active Pending
- 1975-11-05 DK DK496975A patent/DK496975A/da unknown
- 1975-11-05 NL NL7512960A patent/NL7512960A/xx not_active Application Discontinuation
- 1975-11-05 ES ES442360A patent/ES442360A1/es not_active Expired
- 1975-11-05 LU LU73730A patent/LU73730A1/xx unknown
- 1975-11-05 BE BE1006996A patent/BE835299A/xx unknown
- 1975-11-06 FR FR7533931A patent/FR2290445A1/fr active Granted
-
1976
- 1976-09-29 ES ES451958A patent/ES451958A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DK496975A (da) | 1976-05-07 |
| ES451958A1 (es) | 1977-10-01 |
| BE835299A (fr) | 1976-05-05 |
| IE41799L (en) | 1976-05-06 |
| JPS5170790A (en) | 1976-06-18 |
| FR2290445A1 (fr) | 1976-06-04 |
| FR2290445B1 (https=) | 1978-05-12 |
| ES442360A1 (es) | 1977-04-01 |
| NL7512960A (nl) | 1976-05-10 |
| GB1520479A (en) | 1978-08-09 |
| DE2546503A1 (de) | 1976-05-13 |
| LU73730A1 (https=) | 1976-09-06 |
| CA1050010A (en) | 1979-03-06 |
| GB1520480A (en) | 1978-08-09 |
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