DD207720A5 - Verfahren zur herstellung von 7 beta-acylamido-3-cephem-4-carbonsaeureverbindungen - Google Patents
Verfahren zur herstellung von 7 beta-acylamido-3-cephem-4-carbonsaeureverbindungen Download PDFInfo
- Publication number
- DD207720A5 DD207720A5 DD83250223A DD25022383A DD207720A5 DD 207720 A5 DD207720 A5 DD 207720A5 DD 83250223 A DD83250223 A DD 83250223A DD 25022383 A DD25022383 A DD 25022383A DD 207720 A5 DD207720 A5 DD 207720A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- lower alkyl
- ethyl
- cephem
- group
- formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 61
- 238000004519 manufacturing process Methods 0.000 title description 4
- -1 CARBOXYL Chemical class 0.000 claims abstract description 1226
- 150000001875 compounds Chemical class 0.000 claims abstract description 295
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 47
- 150000002367 halogens Chemical class 0.000 claims abstract description 47
- 238000002360 preparation method Methods 0.000 claims abstract description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 35
- 239000001257 hydrogen Substances 0.000 claims abstract description 34
- 150000004677 hydrates Chemical class 0.000 claims abstract description 12
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 11
- 150000001721 carbon Chemical class 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 250
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 131
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 107
- 239000000460 chlorine Substances 0.000 claims description 101
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 99
- 239000002253 acid Substances 0.000 claims description 78
- 150000003839 salts Chemical class 0.000 claims description 74
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 73
- 239000000203 mixture Substances 0.000 claims description 65
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 57
- 125000000524 functional group Chemical group 0.000 claims description 45
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 44
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 36
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000002252 acyl group Chemical group 0.000 claims description 32
- 239000003795 chemical substances by application Substances 0.000 claims description 31
- 238000005917 acylation reaction Methods 0.000 claims description 30
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 30
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 125000006239 protecting group Chemical group 0.000 claims description 29
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 28
- 229910052801 chlorine Inorganic materials 0.000 claims description 28
- 150000002431 hydrogen Chemical group 0.000 claims description 24
- 125000004423 acyloxy group Chemical group 0.000 claims description 21
- 125000001589 carboacyl group Chemical group 0.000 claims description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 18
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
- 125000003282 alkyl amino group Chemical group 0.000 claims description 15
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 15
- 150000003254 radicals Chemical group 0.000 claims description 15
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbamic acid group Chemical class C(N)(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 13
- 238000005694 sulfonylation reaction Methods 0.000 claims description 13
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 125000004468 heterocyclylthio group Chemical group 0.000 claims description 11
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 10
- 125000000656 azaniumyl group Chemical group [H][N+]([H])([H])[*] 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 8
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 7
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 7
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 7
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
- 125000001246 bromo group Chemical group Br* 0.000 claims description 7
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 7
- 230000036961 partial effect Effects 0.000 claims description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 230000004962 physiological condition Effects 0.000 claims description 6
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
- 125000005999 2-bromoethyl group Chemical group 0.000 claims description 4
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- IKWLIQXIPRUIDU-ZCFIWIBFSA-N (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CCS[C@@H]2CC(=O)N12 IKWLIQXIPRUIDU-ZCFIWIBFSA-N 0.000 claims description 3
- 229910014033 C-OH Inorganic materials 0.000 claims description 3
- 229910014570 C—OH Inorganic materials 0.000 claims description 3
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 claims description 3
- 125000003705 anilinocarbonyl group Chemical group O=C([*])N([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 claims description 3
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims description 3
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 3
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 3
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 3
- 150000003460 sulfonic acids Chemical class 0.000 claims description 3
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
- 239000005977 Ethylene Substances 0.000 claims description 2
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- HCQABJQZDYSTJH-QFSRMBNQSA-N (6r)-4-acetamido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CC(NC(=O)C)S[C@@H]2CC(=O)N21 HCQABJQZDYSTJH-QFSRMBNQSA-N 0.000 claims 1
- QIKYZXDTTPVVAC-UHFFFAOYSA-N 4-Aminobenzamide Chemical compound NC(=O)C1=CC=C(N)C=C1 QIKYZXDTTPVVAC-UHFFFAOYSA-N 0.000 claims 1
- LEMAGHDBYUXCEB-JOAULVNJSA-N C(N)(=O)OCC=1CS[C@H]2N(C1C(=O)O)C([C@H]2NC([C@@H](NS(=O)(=O)C)C=2N=C(SC2)N)=O)=O Chemical compound C(N)(=O)OCC=1CS[C@H]2N(C1C(=O)O)C([C@H]2NC([C@@H](NS(=O)(=O)C)C=2N=C(SC2)N)=O)=O LEMAGHDBYUXCEB-JOAULVNJSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 230000003115 biocidal effect Effects 0.000 abstract description 6
- 244000005700 microbiome Species 0.000 abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 4
- 208000035473 Communicable disease Diseases 0.000 abstract 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical class [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 abstract 1
- 239000013067 intermediate product Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 233
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 228
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 153
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 126
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 116
- 239000000243 solution Substances 0.000 description 112
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 111
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 109
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 94
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 91
- 239000000741 silica gel Substances 0.000 description 89
- 229910002027 silica gel Inorganic materials 0.000 description 89
- 235000002639 sodium chloride Nutrition 0.000 description 80
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 78
- 235000019439 ethyl acetate Nutrition 0.000 description 77
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 67
- 229960000583 acetic acid Drugs 0.000 description 65
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
- 239000007858 starting material Substances 0.000 description 60
- 229910001868 water Inorganic materials 0.000 description 60
- 238000000354 decomposition reaction Methods 0.000 description 57
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 54
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 53
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 47
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 46
- 239000002904 solvent Substances 0.000 description 43
- 125000003277 amino group Chemical group 0.000 description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- 239000003480 eluent Substances 0.000 description 35
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 33
- 229910052938 sodium sulfate Inorganic materials 0.000 description 31
- 235000011152 sodium sulphate Nutrition 0.000 description 31
- 238000003756 stirring Methods 0.000 description 30
- 239000012043 crude product Substances 0.000 description 29
- 150000002148 esters Chemical class 0.000 description 29
- 125000000623 heterocyclic group Chemical group 0.000 description 29
- 239000002585 base Substances 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 28
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 26
- 125000004432 carbon atom Chemical group C* 0.000 description 26
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 26
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 25
- 229910052757 nitrogen Inorganic materials 0.000 description 24
- 125000001424 substituent group Chemical group 0.000 description 24
- 238000001035 drying Methods 0.000 description 23
- 230000010933 acylation Effects 0.000 description 22
- 239000000725 suspension Substances 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- NYYBPASOTOAXQW-VQIMIIECSA-N benzhydryl (6r,7r)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1[C@@H](C(N11)=O)N)CC=C1C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 NYYBPASOTOAXQW-VQIMIIECSA-N 0.000 description 21
- 239000000843 powder Substances 0.000 description 21
- 239000011734 sodium Substances 0.000 description 21
- 159000000000 sodium salts Chemical class 0.000 description 21
- 150000008064 anhydrides Chemical class 0.000 description 20
- 238000012512 characterization method Methods 0.000 description 19
- 229920006395 saturated elastomer Polymers 0.000 description 19
- 239000011780 sodium chloride Substances 0.000 description 19
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 230000035484 reaction time Effects 0.000 description 18
- SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 18
- 229910052783 alkali metal Inorganic materials 0.000 description 17
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 16
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 16
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
- 239000012299 nitrogen atmosphere Substances 0.000 description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- 238000001704 evaporation Methods 0.000 description 15
- 150000007522 mineralic acids Chemical class 0.000 description 15
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 14
- 238000009833 condensation Methods 0.000 description 14
- 230000005494 condensation Effects 0.000 description 14
- 230000008020 evaporation Effects 0.000 description 14
- 229910052708 sodium Inorganic materials 0.000 description 14
- 125000001931 aliphatic group Chemical group 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 230000002378 acidificating effect Effects 0.000 description 12
- 150000007513 acids Chemical class 0.000 description 12
- 150000001340 alkali metals Chemical class 0.000 description 12
- 230000007717 exclusion Effects 0.000 description 12
- 230000007935 neutral effect Effects 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 11
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Inorganic materials [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 11
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 10
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- 239000004305 biphenyl Substances 0.000 description 10
- 235000010290 biphenyl Nutrition 0.000 description 10
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 10
- 229910052751 metal Inorganic materials 0.000 description 10
- 150000004702 methyl esters Chemical class 0.000 description 10
- 230000003647 oxidation Effects 0.000 description 10
- 238000007254 oxidation reaction Methods 0.000 description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
- 238000006722 reduction reaction Methods 0.000 description 10
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- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical class [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 1
- 229940112669 cuprous oxide Drugs 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- VJCWGXGMXAVKJU-UHFFFAOYSA-N cyclohexyl cyclohexanecarboxylate Chemical compound C1CCCCC1C(=O)OC1CCCCC1 VJCWGXGMXAVKJU-UHFFFAOYSA-N 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- SNRGJXWEFUNIJP-UHFFFAOYSA-N dichloromethane;methyl acetate Chemical compound ClCCl.COC(C)=O SNRGJXWEFUNIJP-UHFFFAOYSA-N 0.000 description 1
- IMDXZWRLUZPMDH-UHFFFAOYSA-N dichlorophenylphosphine Chemical compound ClP(Cl)C1=CC=CC=C1 IMDXZWRLUZPMDH-UHFFFAOYSA-N 0.000 description 1
- UCQFCFPECQILOL-UHFFFAOYSA-N diethyl hydrogen phosphate Chemical compound CCOP(O)(=O)OCC UCQFCFPECQILOL-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LIKFHECYJZWXFJ-UHFFFAOYSA-N dimethyldichlorosilane Chemical compound C[Si](C)(Cl)Cl LIKFHECYJZWXFJ-UHFFFAOYSA-N 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960002089 ferrous chloride Drugs 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 125000004969 haloethyl group Chemical group 0.000 description 1
- 150000005826 halohydrocarbons Chemical class 0.000 description 1
- 125000004970 halomethyl group Chemical group 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- HJLHTTJLVALHOP-UHFFFAOYSA-N hexane;hydron;chloride Chemical compound Cl.CCCCCC HJLHTTJLVALHOP-UHFFFAOYSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- CUPFNGOKRMWUOO-UHFFFAOYSA-N hydron;difluoride Chemical compound F.F CUPFNGOKRMWUOO-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Inorganic materials Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000010952 in-situ formation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910021432 inorganic complex Inorganic materials 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910001867 inorganic solvent Inorganic materials 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate Chemical compound [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- PPNAOCWZXJOHFK-UHFFFAOYSA-N manganese(2+);oxygen(2-) Chemical class [O-2].[Mn+2] PPNAOCWZXJOHFK-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- LLCOIQRNSJBFSN-UHFFFAOYSA-N methane;sulfurochloridic acid Chemical compound C.OS(Cl)(=O)=O LLCOIQRNSJBFSN-UHFFFAOYSA-N 0.000 description 1
- CHAOSTCZCACQQP-UHFFFAOYSA-N methyl 2-(methanesulfonamido)acetate Chemical compound COC(=O)CNS(C)(=O)=O CHAOSTCZCACQQP-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- GRKXKNLRBZVLSN-UHFFFAOYSA-N methylamino acetate Chemical compound CNOC(C)=O GRKXKNLRBZVLSN-UHFFFAOYSA-N 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- YYHPEVZFVMVUNJ-UHFFFAOYSA-N n,n-diethylethanamine;sulfur trioxide Chemical compound O=S(=O)=O.CCN(CC)CC YYHPEVZFVMVUNJ-UHFFFAOYSA-N 0.000 description 1
- JGSYWZJNFXZTKV-UHFFFAOYSA-N n,n-dimethyl-2-(tetrazol-1-yl)ethanamine Chemical compound CN(C)CCN1C=NN=N1 JGSYWZJNFXZTKV-UHFFFAOYSA-N 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
- LWFWUJCJKPUZLV-UHFFFAOYSA-N n-trimethylsilylacetamide Chemical compound CC(=O)N[Si](C)(C)C LWFWUJCJKPUZLV-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002903 organophosphorus compounds Chemical class 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000000369 oxido group Chemical group [*]=O 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 150000004968 peroxymonosulfuric acids Chemical class 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- RYIOLWQRQXDECZ-UHFFFAOYSA-N phosphinous acid Chemical compound PO RYIOLWQRQXDECZ-UHFFFAOYSA-N 0.000 description 1
- XRBCRPZXSCBRTK-UHFFFAOYSA-N phosphonous acid Chemical compound OPO XRBCRPZXSCBRTK-UHFFFAOYSA-N 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- HEZHYQDYRPUXNJ-UHFFFAOYSA-L potassium dithionite Chemical compound [K+].[K+].[O-]S(=O)S([O-])=O HEZHYQDYRPUXNJ-UHFFFAOYSA-L 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 229940116357 potassium thiocyanate Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical compound OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Inorganic materials [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- ICDOJLHGNRCMRX-UHFFFAOYSA-M sodium;(5-sulfanylidene-2h-tetrazol-1-yl)methanesulfonate Chemical compound [Na]OS(=O)(=O)CN1N=NN=C1S ICDOJLHGNRCMRX-UHFFFAOYSA-M 0.000 description 1
- HSFQBFMEWSTNOW-UHFFFAOYSA-N sodium;carbanide Chemical group [CH3-].[Na+] HSFQBFMEWSTNOW-UHFFFAOYSA-N 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- QSUJAUYJBJRLKV-UHFFFAOYSA-M tetraethylazanium;fluoride Chemical compound [F-].CC[N+](CC)(CC)CC QSUJAUYJBJRLKV-UHFFFAOYSA-M 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
- 239000001585 thymus vulgaris Substances 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 150000003609 titanium compounds Chemical class 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 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 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/568—Four-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH256882 | 1982-04-27 | ||
CH650482 | 1982-11-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
DD207720A5 true DD207720A5 (de) | 1984-03-14 |
Family
ID=25690804
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DD83250223A DD207720A5 (de) | 1982-04-27 | 1983-04-26 | Verfahren zur herstellung von 7 beta-acylamido-3-cephem-4-carbonsaeureverbindungen |
Country Status (12)
Country | Link |
---|---|
EP (1) | EP0092830A3 (fi) |
AU (1) | AU1395183A (fi) |
DD (1) | DD207720A5 (fi) |
DK (1) | DK185383A (fi) |
ES (2) | ES8504818A1 (fi) |
FI (1) | FI831381L (fi) |
GB (1) | GB2118942B (fi) |
GR (1) | GR78190B (fi) |
HU (1) | HU188459B (fi) |
IL (1) | IL68477A0 (fi) |
NO (1) | NO831470L (fi) |
PT (1) | PT76597B (fi) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7271188B2 (en) | 2003-06-12 | 2007-09-18 | Chugai Seikayu Kabushiki Kaisha | Imidazolidine derivatives |
JP5625614B2 (ja) | 2010-08-20 | 2014-11-19 | セイコーエプソン株式会社 | 光フィルター、光フィルターモジュール、分光測定器および光機器 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3270000A (en) * | 1962-10-29 | 1966-08-30 | Squibb & Sons Inc | Protected amino acid derivatives of 7-aminocephalosporanic acid |
DE2724073A1 (de) * | 1976-06-03 | 1977-12-22 | Fujisawa Pharmaceutical Co | 3,7-disubstituierte 3-cephem-4- carbonsaeuren und sie enthaltende pharmazeutische zubereitungen |
-
1983
- 1983-04-22 FI FI831381A patent/FI831381L/fi not_active Application Discontinuation
- 1983-04-25 EP EP83104037A patent/EP0092830A3/de not_active Withdrawn
- 1983-04-25 GB GB08311222A patent/GB2118942B/en not_active Expired
- 1983-04-25 ES ES521824A patent/ES8504818A1/es not_active Expired
- 1983-04-25 IL IL68477A patent/IL68477A0/xx unknown
- 1983-04-26 DK DK185383A patent/DK185383A/da not_active Application Discontinuation
- 1983-04-26 PT PT76597A patent/PT76597B/pt unknown
- 1983-04-26 AU AU13951/83A patent/AU1395183A/en not_active Abandoned
- 1983-04-26 HU HU831436A patent/HU188459B/hu unknown
- 1983-04-26 NO NO831470A patent/NO831470L/no unknown
- 1983-04-26 DD DD83250223A patent/DD207720A5/de unknown
- 1983-04-28 GR GR71184A patent/GR78190B/el unknown
-
1984
- 1984-08-16 ES ES535195A patent/ES8506727A1/es not_active Expired
Also Published As
Publication number | Publication date |
---|---|
ES521824A0 (es) | 1985-05-01 |
FI831381L (fi) | 1983-10-28 |
IL68477A0 (en) | 1983-07-31 |
PT76597A (en) | 1983-05-01 |
EP0092830A3 (de) | 1984-12-27 |
ES8504818A1 (es) | 1985-05-01 |
EP0092830A2 (de) | 1983-11-02 |
DK185383D0 (da) | 1983-04-26 |
GB2118942B (en) | 1985-07-24 |
GR78190B (fi) | 1984-09-26 |
GB8311222D0 (en) | 1983-06-02 |
GB2118942A (en) | 1983-11-09 |
DK185383A (da) | 1983-10-28 |
ES535195A0 (es) | 1985-08-01 |
PT76597B (en) | 1986-03-12 |
ES8506727A1 (es) | 1985-08-01 |
NO831470L (no) | 1983-10-28 |
FI831381A0 (fi) | 1983-04-22 |
HU188459B (en) | 1986-04-28 |
AU1395183A (en) | 1983-11-03 |
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