CS262674B2 - Process for preparing heat stable crystalline cephalosporines - Google Patents
Process for preparing heat stable crystalline cephalosporines Download PDFInfo
- Publication number
- CS262674B2 CS262674B2 CS866115A CS611586A CS262674B2 CS 262674 B2 CS262674 B2 CS 262674B2 CS 866115 A CS866115 A CS 866115A CS 611586 A CS611586 A CS 611586A CS 262674 B2 CS262674 B2 CS 262674B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- formula
- trichlorotrifluoroethane
- compound
- minutes
- trimethylsilyl
- Prior art date
Links
- 125000001271 cephalosporin group Chemical group 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 105
- 238000000034 method Methods 0.000 claims abstract description 67
- 229930186147 Cephalosporin Natural products 0.000 claims abstract description 10
- 229940124587 cephalosporin Drugs 0.000 claims abstract description 10
- 150000001780 cephalosporins Chemical class 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 239000000543 intermediate Substances 0.000 claims abstract description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 147
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 75
- 238000006243 chemical reaction Methods 0.000 claims description 67
- AJDIZQLSFPQPEY-UHFFFAOYSA-N 1,1,2-Trichlorotrifluoroethane Chemical compound FC(F)(Cl)C(F)(Cl)Cl AJDIZQLSFPQPEY-UHFFFAOYSA-N 0.000 claims description 50
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 45
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 claims description 44
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 28
- BOSAWIQFTJIYIS-UHFFFAOYSA-N 1,1,1-trichloro-2,2,2-trifluoroethane Chemical compound FC(F)(F)C(Cl)(Cl)Cl BOSAWIQFTJIYIS-UHFFFAOYSA-N 0.000 claims description 12
- 239000007858 starting material Substances 0.000 claims description 10
- 229910000043 hydrogen iodide Chemical group 0.000 claims description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 6
- 230000020477 pH reduction Effects 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 23
- 229910052717 sulfur Inorganic materials 0.000 abstract description 6
- 239000003242 anti bacterial agent Substances 0.000 abstract description 3
- 229940088710 antibiotic agent Drugs 0.000 abstract description 3
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 3
- 125000004434 sulfur atom Chemical group 0.000 abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 2
- 239000000725 suspension Substances 0.000 description 62
- 239000000243 solution Substances 0.000 description 55
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- 238000003756 stirring Methods 0.000 description 37
- 239000000203 mixture Substances 0.000 description 35
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 34
- -1 amino-substituted oxazole Chemical class 0.000 description 34
- 239000011541 reaction mixture Substances 0.000 description 34
- HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 description 32
- 239000000047 product Substances 0.000 description 30
- 238000011141 high resolution liquid chromatography Methods 0.000 description 29
- 239000000463 material Substances 0.000 description 28
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 25
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 24
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 24
- 239000000523 sample Substances 0.000 description 21
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 239000005909 Kieselgur Substances 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 17
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 16
- 239000012299 nitrogen atmosphere Substances 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 238000001228 spectrum Methods 0.000 description 16
- 239000002808 molecular sieve Substances 0.000 description 15
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 15
- 239000011343 solid material Substances 0.000 description 15
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 14
- 239000012043 crude product Substances 0.000 description 14
- 238000001816 cooling Methods 0.000 description 13
- 239000012065 filter cake Substances 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical group CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 239000008346 aqueous phase Substances 0.000 description 11
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 11
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 10
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 230000010933 acylation Effects 0.000 description 7
- 238000005917 acylation reaction Methods 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 239000001569 carbon dioxide Substances 0.000 description 7
- 229910002092 carbon dioxide Inorganic materials 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- 150000002148 esters Chemical group 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000013058 crude material Substances 0.000 description 6
- 239000008367 deionised water Substances 0.000 description 6
- 229910021641 deionized water Inorganic materials 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000002002 slurry Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- FPVUWZFFEGYCGB-UHFFFAOYSA-N 5-methyl-3h-1,3,4-thiadiazole-2-thione Chemical compound CC1=NN=C(S)S1 FPVUWZFFEGYCGB-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000012038 nucleophile Substances 0.000 description 4
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 3
- ZDZCDSDZYVRTEZ-ZWNOBZJWSA-N trimethylsilyl (6r,7r)-3-(iodomethyl)-8-oxo-7-(trimethylsilyloxycarbonylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S1CC(CI)=C(C(=O)O[Si](C)(C)C)N2C(=O)[C@@H](NC(=O)O[Si](C)(C)C)[C@H]21 ZDZCDSDZYVRTEZ-ZWNOBZJWSA-N 0.000 description 3
- ATACKIKFCHWKPX-FOUAAFFMSA-N (6R)-4-amino-3-(iodomethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1[C@@H]2N(C1=O)C(=C(C(S2)N)CI)C(=O)O ATACKIKFCHWKPX-FOUAAFFMSA-N 0.000 description 2
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- KRNSYSYRLQDHDK-UHFFFAOYSA-N 6,7-dihydro-5h-cyclopenta[b]pyridine Chemical compound C1=CN=C2CCCC2=C1 KRNSYSYRLQDHDK-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- IDIOJRGTRFRIJL-UHFFFAOYSA-N iodosilane Chemical compound I[SiH3] IDIOJRGTRFRIJL-UHFFFAOYSA-N 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- BJDYCCHRZIFCGN-UHFFFAOYSA-N pyridin-1-ium;iodide Chemical group I.C1=CC=NC=C1 BJDYCCHRZIFCGN-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
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- 125000001424 substituent group Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- NLARCUDOUOQRPB-WTKPLQERSA-N (2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetic acid Chemical compound CO\N=C(/C(O)=O)C1=CSC(N)=N1 NLARCUDOUOQRPB-WTKPLQERSA-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
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- NFHQYWPOTLXIQP-UHFFFAOYSA-N 1-methylpyrazolidine Chemical compound CN1CCCN1 NFHQYWPOTLXIQP-UHFFFAOYSA-N 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- NDVMCQUOSYOQMZ-UHFFFAOYSA-N 2,2-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)C(C(N)=O)[Si](C)(C)C NDVMCQUOSYOQMZ-UHFFFAOYSA-N 0.000 description 1
- VTGOYLLGHIXKHA-UHFFFAOYSA-N 4-iodo-1,2,3-trimethylsiline Chemical compound IC1=C(C(=[Si](C=C1)C)C)C VTGOYLLGHIXKHA-UHFFFAOYSA-N 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
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- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
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- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
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- 238000010438 heat treatment Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
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- AWJUIBRHMBBTKR-UHFFFAOYSA-O isoquinolin-2-ium Chemical class C1=[NH+]C=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-O 0.000 description 1
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
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- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- HQOQSFITXGQQDM-SSDOTTSWSA-N methyl (6R)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound COC(=O)C1=CCS[C@@H]2CC(=O)N12 HQOQSFITXGQQDM-SSDOTTSWSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 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
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- YAGXZDADEJXXMM-UHFFFAOYSA-M potassium chloride hydrate Chemical compound [OH-].Cl.[K+] YAGXZDADEJXXMM-UHFFFAOYSA-M 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000012066 reaction slurry Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- QHADFWIYLZWUOD-JLOHTSLTSA-N trimethylsilyl (6r)-3-(iodomethyl)-8-oxo-7-(trimethylsilylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S1CC(CI)=C(C(=O)O[Si](C)(C)C)N2C(=O)C(N[Si](C)(C)C)[C@H]21 QHADFWIYLZWUOD-JLOHTSLTSA-N 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/38—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof
- C07D501/46—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof with the 7-amino radical acylated by carboxylic acids containing hetero rings
-
- 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
- C07D501/02—Preparation
- C07D501/04—Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
-
- 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
- C07D501/18—7-Aminocephalosporanic or substituted 7-aminocephalosporanic acids
-
- 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
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/38—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS879686A CS262698B2 (cs) | 1985-08-20 | 1987-12-22 | Způsob výroby teplotně stálých krystalických cefalosporinů |
| CS879687A CS262699B2 (cs) | 1985-08-20 | 1987-12-22 | Způsob výroby stabilních krystalických ceíailospoirinů obecného vzorce I, kde X je chlorovodík nebo jodbvodík, spočívající v reakci sloučeniny vzorce VL s roztokem sloučeniny vzorce IVa v 1,1,2-trichlortrifluore- thanu, v odštěpení sílyfových skupin, působením nižšího alkanolu a v okyselení produktu chlorovodíkem nebo jodovodíkem. Vyrobené sloučeniny slouží jako meziprodukty pro přípravu cefalosporinových antibiotik se širokým spektrem účinku. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US76756185A | 1985-08-20 | 1985-08-20 | |
| US06/882,107 US4714760A (en) | 1985-08-20 | 1986-07-11 | Cephalosporin intermediates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS611586A2 CS611586A2 (en) | 1988-08-16 |
| CS262674B2 true CS262674B2 (en) | 1989-03-14 |
Family
ID=27117927
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS866115A CS262674B2 (en) | 1985-08-20 | 1986-08-20 | Process for preparing heat stable crystalline cephalosporines |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US4714760A (ja) |
| EP (1) | EP0233271B1 (ja) |
| JP (1) | JPH0615549B2 (ja) |
| KR (1) | KR910000419B1 (ja) |
| AR (1) | AR241408A1 (ja) |
| AT (1) | ATE87000T1 (ja) |
| CA (1) | CA1282408C (ja) |
| CS (1) | CS262674B2 (ja) |
| CY (1) | CY1848A (ja) |
| EG (1) | EG18205A (ja) |
| FI (1) | FI89051C (ja) |
| HK (1) | HK110295A (ja) |
| HU (1) | HU201080B (ja) |
| WO (1) | WO1987001116A1 (ja) |
| YU (1) | YU44810B (ja) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0827520B2 (ja) * | 1986-07-12 | 1996-03-21 | 富士写真フイルム株式会社 | ハロゲン化銀カラ−写真感光材料の処理方法 |
| ES2063129T3 (es) * | 1988-06-22 | 1995-01-01 | Lilly Co Eli | Intermedio de la 1-carba(detia)cefalosporina. |
| US4935508A (en) * | 1988-08-23 | 1990-06-19 | Bristol-Myers Company | Process for cephem prodrug esters |
| YU81692A (sh) * | 1991-09-10 | 1995-03-27 | Bristol-Myers Co. | Postupak za proizvodnju cefalosporinskog antibiotika |
| MY108872A (en) * | 1991-09-10 | 1996-11-30 | Bristol Myers Squibb Co | Preparation of a cephalosporin antibiotic using the syn-isomer of a thiazolyl intermediate. |
| CA2099692C (en) * | 1992-07-24 | 2003-09-30 | Gary M. F. Lim | Process for preparing cephalosporin intermediates |
| ATE244248T1 (de) * | 1996-04-12 | 2003-07-15 | Takeda Chemical Industries Ltd | Herstellung von amino cephalosporansäurederivaten |
| WO2006008749A1 (en) * | 2004-07-16 | 2006-01-26 | Hetero Drugs Limited | Process for preparing pure cephalosporine intermediates |
| WO2006075244A2 (en) * | 2005-01-17 | 2006-07-20 | Orchid Chemicals & Pharmaceuticals Ltd | Improved process for the preparation of cephalosporin antibiotic intermediate |
| ITMI20051684A1 (it) * | 2005-09-13 | 2007-03-14 | Harvest Lodge Ltd | Procedimento per la produzione del dicloridrato di amminoacidi |
| ITMI20060422A1 (it) * | 2006-03-09 | 2007-09-10 | Harvest Lodge Ltd | Procedimento diretto per la produzione del dicloridrato di un amminoacido |
| CN102391288B (zh) * | 2011-12-03 | 2013-09-18 | 齐鲁安替制药有限公司 | 头孢匹罗中间体及头孢匹罗的制备方法 |
| CN102391289B (zh) * | 2011-12-03 | 2013-09-18 | 齐鲁安替制药有限公司 | 头孢他啶中间体及头孢他啶的合成方法 |
| CN102627659A (zh) * | 2012-04-17 | 2012-08-08 | 黑龙江豪运精细化工有限公司 | 一种头孢哌酮中间体7-tmca的制备方法 |
| CN102633813A (zh) * | 2012-04-17 | 2012-08-15 | 黑龙江豪运精细化工有限公司 | 一种头孢唑林钠中间体tda的制备方法 |
| CN107201391B (zh) * | 2017-07-04 | 2020-07-07 | 吉林省爱诺德生物工程有限公司 | 一种盐酸头孢吡肟的合成方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4182863A (en) * | 1974-09-03 | 1980-01-08 | Bristol-Myers Company | 7-Amino-3-(1-carboxymethyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid |
| US4093723A (en) * | 1976-05-19 | 1978-06-06 | Smithkline Corporation | 7-Acyl-3-(sulfonic acid and sulfamoyl substituted tetrazolyl thiomethyl) cephalosporins |
| US4029655A (en) * | 1975-04-11 | 1977-06-14 | Eli Lilly And Company | Method of preparing stable sterile crystalline cephalosporins for parenteral administration |
| GB1591439A (en) * | 1976-10-01 | 1981-06-24 | Glaxo Operations Ltd | 7-syn (oxyimino -acylamido) cephalosporins |
| GB2052490B (en) * | 1979-05-25 | 1983-09-07 | Glaxo Group Ltd | Intermediates for use in the preparation of cephalosporin antibiotics |
| EP0051824B1 (en) * | 1980-11-11 | 1986-01-15 | Takeda Chemical Industries, Ltd. | Improvement in the method for producing 7-aminocephem compounds |
| IT8026945A0 (it) * | 1980-12-24 | 1980-12-24 | Isf Spa | Chetoidrossiimminocefalosporine. |
| US4336253A (en) * | 1981-03-11 | 1982-06-22 | Eli Lilly And Company | Cephalosporin antibiotics |
| DE3118732A1 (de) * | 1981-05-12 | 1982-12-02 | Hoechst Ag, 6000 Frankfurt | Cephalosporinderivate und verfahren zu ihrer herstellung |
| GR76701B (ja) * | 1981-09-08 | 1984-08-29 | Lilly Co Eli | |
| US4406899A (en) * | 1982-03-04 | 1983-09-27 | Bristol-Myers Company | Cephalosporins |
| US4499088A (en) * | 1983-01-04 | 1985-02-12 | Fujisawa Pharmaceutical Co., Ltd. | Cephem compounds |
| DE3316798A1 (de) * | 1983-05-07 | 1984-11-08 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von cephemverbindungen |
| US4540779A (en) * | 1983-06-20 | 1985-09-10 | Eli Lilly And Company | Crystalline 7-(R)-amino-3-(1'pyridiniummethyl)-ceph-3-em-4-carboxylate monohydrochloride monohydrate compound |
| US4659812A (en) * | 1985-08-20 | 1987-04-21 | Bristol-Myers Company | Cephalosporin intermediates |
-
1986
- 1986-07-11 US US06/882,107 patent/US4714760A/en not_active Expired - Lifetime
- 1986-08-12 WO PCT/US1986/001637 patent/WO1987001116A1/en active IP Right Grant
- 1986-08-12 HU HU864052A patent/HU201080B/hu unknown
- 1986-08-12 EP EP86905495A patent/EP0233271B1/en not_active Expired - Lifetime
- 1986-08-12 JP JP61504556A patent/JPH0615549B2/ja not_active Expired - Lifetime
- 1986-08-12 KR KR1019870700340A patent/KR910000419B1/ko not_active IP Right Cessation
- 1986-08-12 AT AT86905495T patent/ATE87000T1/de not_active IP Right Cessation
- 1986-08-19 CA CA000516259A patent/CA1282408C/en not_active Expired - Lifetime
- 1986-08-20 AR AR86304973A patent/AR241408A1/es active
- 1986-08-20 EG EG527/86A patent/EG18205A/xx active
- 1986-08-20 CS CS866115A patent/CS262674B2/cs not_active IP Right Cessation
-
1987
- 1987-04-16 FI FI871693A patent/FI89051C/fi not_active IP Right Cessation
- 1987-08-28 YU YU1603/87A patent/YU44810B/xx unknown
-
1995
- 1995-07-06 HK HK110295A patent/HK110295A/xx not_active IP Right Cessation
-
1996
- 1996-03-08 CY CY184896A patent/CY1848A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR910000419B1 (ko) | 1991-01-25 |
| HU201080B (en) | 1990-09-28 |
| FI871693A (fi) | 1987-04-16 |
| HK110295A (en) | 1995-07-14 |
| YU160387A (en) | 1988-08-31 |
| EG18205A (en) | 1993-10-30 |
| YU44810B (en) | 1991-02-28 |
| FI89051B (fi) | 1993-04-30 |
| FI871693A0 (fi) | 1987-04-16 |
| EP0233271A4 (en) | 1988-10-20 |
| CY1848A (en) | 1996-03-08 |
| JPH0615549B2 (ja) | 1994-03-02 |
| EP0233271B1 (en) | 1993-03-17 |
| KR870700628A (ko) | 1987-12-30 |
| HUT43853A (en) | 1987-12-28 |
| CS611586A2 (en) | 1988-08-16 |
| FI89051C (fi) | 1993-08-10 |
| AR241408A1 (es) | 1992-07-31 |
| US4714760A (en) | 1987-12-22 |
| JPS62502046A (ja) | 1987-08-13 |
| ATE87000T1 (de) | 1993-04-15 |
| EP0233271A1 (en) | 1987-08-26 |
| CA1282408C (en) | 1991-04-02 |
| WO1987001116A1 (en) | 1987-02-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| IF00 | In force as of 2000-06-30 in czech republic | ||
| MK4A | Patent expired |
Effective date: 20010820 |