CH628051A5 - Process for the preparation of N-alkylated derivatives of thienamycin - Google Patents

Info

Publication number

CH628051A5

CH628051A5 CH1462176A CH1462176A CH628051A5 CH 628051 A5 CH628051 A5 CH 628051A5 CH 1462176 A CH1462176 A CH 1462176A CH 1462176 A CH1462176 A CH 1462176A CH 628051 A5 CH628051 A5 CH 628051A5

Authority

CH

Switzerland

Prior art keywords

carbon atoms

radical

alkyl

group

thienamycin

Prior art date

1975-11-21

Links

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• Global Dossier
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• WKDDRNSBRWANNC-ATRFCDNQSA-N Thienamycin Chemical class C1C(SCCN)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 WKDDRNSBRWANNC-ATRFCDNQSA-N 0.000 title claims description 60
• 238000000034 method Methods 0.000 title claims description 38
• 238000002360 preparation method Methods 0.000 title claims description 31
• -1 alkyl radical Chemical class 0.000 claims description 399
• 125000004432 carbon atom Chemical group C* 0.000 claims description 119
• 229910052757 nitrogen Inorganic materials 0.000 claims description 91
• 125000000217 alkyl group Chemical group 0.000 claims description 71
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 30
• 150000003254 radicals Chemical class 0.000 claims description 30
• 150000003839 salts Chemical class 0.000 claims description 30
• 125000002252 acyl group Chemical group 0.000 claims description 29
• 150000001875 compounds Chemical class 0.000 claims description 27
• 229910052760 oxygen Inorganic materials 0.000 claims description 26
• 125000003118 aryl group Chemical group 0.000 claims description 25
• 239000000460 chlorine Substances 0.000 claims description 23
• 229910052717 sulfur Inorganic materials 0.000 claims description 23
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
• 125000001424 substituent group Chemical group 0.000 claims description 22
• 239000001301 oxygen Substances 0.000 claims description 21
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 20
• 125000003545 alkoxy group Chemical group 0.000 claims description 18
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 17
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 17
• 239000011593 sulfur Substances 0.000 claims description 17
• 229910052801 chlorine Inorganic materials 0.000 claims description 16
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
• 229910052794 bromium Inorganic materials 0.000 claims description 14
• 229910052731 fluorine Inorganic materials 0.000 claims description 14
• 229910052736 halogen Inorganic materials 0.000 claims description 14
• 150000002367 halogens Chemical class 0.000 claims description 14
• 239000002168 alkylating agent Substances 0.000 claims description 13
• 229940100198 alkylating agent Drugs 0.000 claims description 13
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 125000003342 alkenyl group Chemical group 0.000 claims description 11
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
• 239000011737 fluorine Substances 0.000 claims description 9
• 125000000623 heterocyclic group Chemical group 0.000 claims description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
• 125000002950 monocyclic group Chemical group 0.000 claims description 8
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 7
• 125000004429 atom Chemical group 0.000 claims description 7
• 125000004122 cyclic group Chemical group 0.000 claims description 6
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 5
• 125000003277 amino group Chemical group 0.000 claims description 5
• 229910052740 iodine Inorganic materials 0.000 claims description 5
• 239000011630 iodine Substances 0.000 claims description 5
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000001153 fluoro group Chemical group F* 0.000 claims description 4
• 125000006413 ring segment Chemical group 0.000 claims description 4
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
• 150000001450 anions Chemical class 0.000 claims description 3
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
• 150000005840 aryl radicals Chemical class 0.000 claims description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
• 125000005117 dialkylcarbamoyl group Chemical group 0.000 claims description 2
• 125000004043 oxo group Chemical group O=* 0.000 claims description 2
• 125000004434 sulfur atom Chemical group 0.000 claims description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 175
• 239000000203 mixture Substances 0.000 description 86
• 239000000243 solution Substances 0.000 description 86
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 84
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 66
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
• 229910001868 water Inorganic materials 0.000 description 50
• WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 48
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 39
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 32
• 238000006243 chemical reaction Methods 0.000 description 31
• 239000000047 product Substances 0.000 description 29
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
• 229910052739 hydrogen Inorganic materials 0.000 description 28
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
• 239000001257 hydrogen Substances 0.000 description 26
• 239000002609 medium Substances 0.000 description 26
• 239000008367 deionised water Substances 0.000 description 25
• 229910021641 deionized water Inorganic materials 0.000 description 25
• 150000002148 esters Chemical class 0.000 description 24
• 230000002829 reductive effect Effects 0.000 description 24
• 239000002904 solvent Substances 0.000 description 24
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
• 230000003115 biocidal effect Effects 0.000 description 23
• 239000007858 starting material Substances 0.000 description 23
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
• 239000000741 silica gel Substances 0.000 description 22
• 229910002027 silica gel Inorganic materials 0.000 description 22
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 21
• 239000011780 sodium chloride Substances 0.000 description 21
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
• 238000004519 manufacturing process Methods 0.000 description 19
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 19
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
• 239000010410 layer Substances 0.000 description 18
• 239000008363 phosphate buffer Substances 0.000 description 18
• 238000003756 stirring Methods 0.000 description 18
• 239000002253 acid Substances 0.000 description 17
• 239000011541 reaction mixture Substances 0.000 description 17
• 230000000903 blocking effect Effects 0.000 description 16
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
• 239000000706 filtrate Substances 0.000 description 15
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• 239000003242 anti bacterial agent Substances 0.000 description 14
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 14
• 239000000725 suspension Substances 0.000 description 14
• 229940088710 antibiotic agent Drugs 0.000 description 13
• 239000007788 liquid Substances 0.000 description 13
• 239000011347 resin Substances 0.000 description 13
• 229920005989 resin Polymers 0.000 description 13
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 235000019441 ethanol Nutrition 0.000 description 12
• 230000007062 hydrolysis Effects 0.000 description 12
• 238000006460 hydrolysis reaction Methods 0.000 description 12
• 239000002808 molecular sieve Substances 0.000 description 12
• 239000000523 sample Substances 0.000 description 12
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 12
• 239000007787 solid Substances 0.000 description 12
• 241000894007 species Species 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 239000008346 aqueous phase Substances 0.000 description 11
• 239000003795 chemical substances by application Substances 0.000 description 11
• 239000012141 concentrate Substances 0.000 description 11
• 239000012153 distilled water Substances 0.000 description 11
• 238000005984 hydrogenation reaction Methods 0.000 description 11
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 11
• 235000019341 magnesium sulphate Nutrition 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 235000019198 oils Nutrition 0.000 description 11
• 239000000872 buffer Substances 0.000 description 10
• 235000008504 concentrate Nutrition 0.000 description 10
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 150000002431 hydrogen Chemical class 0.000 description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
• 238000004809 thin layer chromatography Methods 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
• 229920001817 Agar Polymers 0.000 description 8
• 241000607132 Salmonella enterica subsp. enterica serovar Gallinarum Species 0.000 description 8
• 239000008272 agar Substances 0.000 description 8
• 150000001408 amides Chemical class 0.000 description 8
• 235000010633 broth Nutrition 0.000 description 8
• 239000003054 catalyst Substances 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• 150000003952 β-lactams Chemical class 0.000 description 8
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical class [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 7
• 239000003513 alkali Substances 0.000 description 7
• 239000002585 base Substances 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 238000010586 diagram Methods 0.000 description 7
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 150000004820 halides Chemical class 0.000 description 7
• 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 7
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 7
• 238000012746 preparative thin layer chromatography Methods 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
• PVCJKHHOXFKFRP-UHFFFAOYSA-N N-acetylethanolamine Chemical compound CC(=O)NCCO PVCJKHHOXFKFRP-UHFFFAOYSA-N 0.000 description 6
• 238000007126 N-alkylation reaction Methods 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
• 150000008065 acid anhydrides Chemical class 0.000 description 6
• 238000005804 alkylation reaction Methods 0.000 description 6
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
• 238000010790 dilution Methods 0.000 description 6
• 239000012895 dilution Substances 0.000 description 6
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 238000000855 fermentation Methods 0.000 description 6
• 230000004151 fermentation Effects 0.000 description 6
• 239000000395 magnesium oxide Substances 0.000 description 6
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
• 239000012071 phase Substances 0.000 description 6
• 241000894006 Bacteria Species 0.000 description 5
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
• 244000286779 Hansenula anomala Species 0.000 description 5
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 5
• 230000029936 alkylation Effects 0.000 description 5
• 150000008064 anhydrides Chemical class 0.000 description 5
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 5
• 125000002619 bicyclic group Chemical group 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 159000000000 sodium salts Chemical class 0.000 description 5
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 4
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
• 101150041968 CDC13 gene Proteins 0.000 description 4
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
• 244000285963 Kluyveromyces fragilis Species 0.000 description 4
• 235000014663 Kluyveromyces fragilis Nutrition 0.000 description 4
• 108010087702 Penicillinase Proteins 0.000 description 4
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 238000005917 acylation reaction Methods 0.000 description 4
• 229910000287 alkaline earth metal oxide Inorganic materials 0.000 description 4
• 150000001412 amines Chemical class 0.000 description 4
• 230000000975 bioactive effect Effects 0.000 description 4
• 239000012267 brine Substances 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
• CRGRWBQSZSQVIE-UHFFFAOYSA-N diazomethylbenzene Chemical compound [N-]=[N+]=CC1=CC=CC=C1 CRGRWBQSZSQVIE-UHFFFAOYSA-N 0.000 description 4
• ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 238000010828 elution Methods 0.000 description 4
• 125000004185 ester group Chemical group 0.000 description 4
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 4
• 238000001704 evaporation Methods 0.000 description 4
• 230000008020 evaporation Effects 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 239000000499 gel Substances 0.000 description 4
• 208000015181 infectious disease Diseases 0.000 description 4
• 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 4
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 4
• 230000007935 neutral effect Effects 0.000 description 4
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 4
• 239000012044 organic layer Substances 0.000 description 4
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
• 229950009506 penicillinase Drugs 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 238000012545 processing Methods 0.000 description 4
• 230000035484 reaction time Effects 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• SPOMEWBVWWDQBC-UHFFFAOYSA-K tripotassium;dihydrogen phosphate;hydrogen phosphate Chemical compound [K+].[K+].[K+].OP(O)([O-])=O.OP([O-])([O-])=O SPOMEWBVWWDQBC-UHFFFAOYSA-K 0.000 description 4
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
• YFLNKMDUUCRCSU-UHFFFAOYSA-N 4-(2-hydroxyethyl)azetidin-2-one Chemical compound OCCC1CC(=O)N1 YFLNKMDUUCRCSU-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 description 3
• 101100219382 Caenorhabditis elegans cah-2 gene Proteins 0.000 description 3
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
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