FI85376C

FI85376C - Foerfarande foer framstaellning av terapeutiskt aktiva 6-(substituerad metylen) penicillanderivat.

Foerfarande foer framstaellning av terapeutiskt aktiva 6-(substituerad metylen) penicillanderivat. Download PDF

Info

Publication number: FI85376C
Authority: FI; Finland
Prior art keywords: formula; compound; mixture; give; nmr
Prior art date: 1984-01-30

Application number

FI850375A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI850375A0 (fi

FI85376B (fi

FI850375L (fi

Inventor

Yuhpyng Liang Chen

Original Assignee

Pfizer

Priority date

1984-01-30

Filing date

1985-01-29

Publication date

1992-04-10

1985-01-29 Application filed by Pfizer filed Critical Pfizer

1985-01-29 Priority to FI902114A priority Critical patent/FI902114A0/fi

1985-01-29 Priority to FI902112A priority patent/FI902112A0/fi

1985-01-29 Priority to FI902113A priority patent/FI902113A7/fi

1985-01-29 Publication of FI850375A0 publication Critical patent/FI850375A0/fi

1985-07-31 Publication of FI850375L publication Critical patent/FI850375L/fi

1991-12-31 Application granted granted Critical

1991-12-31 Publication of FI85376B publication Critical patent/FI85376B/fi

1992-04-10 Publication of FI85376C publication Critical patent/FI85376C/fi

Links

150000001875 compounds Chemical class 0.000 claims description 137
-1 N-methylpyrrolyl Chemical group 0.000 claims description 113
238000000034 method Methods 0.000 claims description 84
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 82
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 76
239000002904 solvent Substances 0.000 claims description 75
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 70
229910052739 hydrogen Inorganic materials 0.000 claims description 52
238000006243 chemical reaction Methods 0.000 claims description 49
239000001257 hydrogen Substances 0.000 claims description 46
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 41
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 40
239000002253 acid Substances 0.000 claims description 37
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 36
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
238000002360 preparation method Methods 0.000 claims description 27
239000000460 chlorine Substances 0.000 claims description 26
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 24
239000011734 sodium Substances 0.000 claims description 24
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
239000000284 extract Substances 0.000 claims description 22
239000007858 starting material Substances 0.000 claims description 22
239000003153 chemical reaction reagent Substances 0.000 claims description 20
230000008569 process Effects 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 20
229910052757 nitrogen Inorganic materials 0.000 claims description 17
239000003054 catalyst Substances 0.000 claims description 16
229910052700 potassium Inorganic materials 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 14
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 13
239000012442 inert solvent Substances 0.000 claims description 12
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 12
229910052794 bromium Inorganic materials 0.000 claims description 10
229910052708 sodium Inorganic materials 0.000 claims description 10
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
239000003960 organic solvent Substances 0.000 claims description 9
KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 claims description 9
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 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
230000003647 oxidation Effects 0.000 claims description 8
238000007254 oxidation reaction Methods 0.000 claims description 8
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims description 6
NFGODEMQGQNUKK-UHFFFAOYSA-M [6-(diethylamino)-9-(2-octadecoxycarbonylphenyl)xanthen-3-ylidene]-diethylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCCOC(=O)C1=CC=CC=C1C1=C2C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C21 NFGODEMQGQNUKK-UHFFFAOYSA-M 0.000 claims description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 6
229910000510 noble metal Inorganic materials 0.000 claims description 6
RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical class OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 claims description 6
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 6
150000003512 tertiary amines Chemical class 0.000 claims description 6
229910000083 tin tetrahydride Inorganic materials 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 5
125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 5
125000002541 furyl group Chemical group 0.000 claims description 5
150000004820 halides Chemical class 0.000 claims description 5
125000006239 protecting group Chemical group 0.000 claims description 5
125000001544 thienyl group Chemical group 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
150000001262 acyl bromides Chemical class 0.000 claims description 4
150000001263 acyl chlorides Chemical class 0.000 claims description 4
229910052783 alkali metal Inorganic materials 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
150000004791 alkyl magnesium halides Chemical class 0.000 claims description 4
125000005336 allyloxy group Chemical group 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
229920002554 vinyl polymer Polymers 0.000 claims description 4
OBETXYAYXDNJHR-UHFFFAOYSA-N 2-Ethylhexanoic acid Chemical compound CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 claims description 3
102000004190 Enzymes Human genes 0.000 claims description 3
108090000790 Enzymes Proteins 0.000 claims description 3
150000001340 alkali metals Chemical class 0.000 claims description 3
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
150000001342 alkaline earth metals Chemical class 0.000 claims description 3
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
125000002091 cationic group Chemical group 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
230000000850 deacetylating effect Effects 0.000 claims description 3
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
239000003495 polar organic solvent Substances 0.000 claims description 3
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 claims description 2
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
239000012286 potassium permanganate Substances 0.000 claims description 2
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 2
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 2
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 claims 1
125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims 1
125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 claims 1
125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 claims 1
125000004414 alkyl thio group Chemical group 0.000 claims 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 227
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 177
239000000203 mixture Substances 0.000 description 165
238000005160 1H NMR spectroscopy Methods 0.000 description 110
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 100
239000000243 solution Substances 0.000 description 85
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
239000000047 product Substances 0.000 description 73
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 71
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 42
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
239000003921 oil Substances 0.000 description 39
235000019198 oils Nutrition 0.000 description 39
239000007787 solid Substances 0.000 description 38
239000000741 silica gel Substances 0.000 description 35
229910002027 silica gel Inorganic materials 0.000 description 35
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
239000003782 beta lactam antibiotic agent Substances 0.000 description 31
150000002148 esters Chemical class 0.000 description 31
239000002132 β-lactam antibiotic Substances 0.000 description 30
229940124586 β-lactam antibiotics Drugs 0.000 description 30
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 21
239000010410 layer Substances 0.000 description 21
239000012044 organic layer Substances 0.000 description 21
238000001704 evaporation Methods 0.000 description 20
238000003756 stirring Methods 0.000 description 20
230000008020 evaporation Effects 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
239000013078 crystal Substances 0.000 description 17
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
JMSRBKPMLUGHCR-UHFFFAOYSA-N bromohydrin Chemical compound BrC[C]1CO1 JMSRBKPMLUGHCR-UHFFFAOYSA-N 0.000 description 16
238000004587 chromatography analysis Methods 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 14
239000012043 crude product Substances 0.000 description 14
239000011591 potassium Substances 0.000 description 14
229960003975 potassium Drugs 0.000 description 14
238000010992 reflux Methods 0.000 description 14
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
150000001299 aldehydes Chemical class 0.000 description 13
238000002329 infrared spectrum Methods 0.000 description 12
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
238000001914 filtration Methods 0.000 description 11
238000007327 hydrogenolysis reaction Methods 0.000 description 11
235000017557 sodium bicarbonate Nutrition 0.000 description 11
229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
JFHLHPSHLUKDLK-UHFFFAOYSA-M (6-chloropyridin-2-yl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].ClC1=CC=CC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 JFHLHPSHLUKDLK-UHFFFAOYSA-M 0.000 description 10
239000003480 eluent Substances 0.000 description 10
239000000706 filtrate Substances 0.000 description 10
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
239000012267 brine Substances 0.000 description 9
238000004440 column chromatography Methods 0.000 description 9
230000000694 effects Effects 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
125000001424 substituent group Chemical group 0.000 description 9
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
229930186147 Cephalosporin Natural products 0.000 description 8
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
229930182555 Penicillin Natural products 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
230000000844 anti-bacterial effect Effects 0.000 description 8
239000003781 beta lactamase inhibitor Substances 0.000 description 8
229940126813 beta-lactamase inhibitor Drugs 0.000 description 8
238000009835 boiling Methods 0.000 description 8
229940124587 cephalosporin Drugs 0.000 description 8
150000001780 cephalosporins Chemical class 0.000 description 8
239000006260 foam Substances 0.000 description 8
238000001727 in vivo Methods 0.000 description 8
244000005700 microbiome Species 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 8
150000003457 sulfones Chemical class 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 7
102000006635 beta-lactamase Human genes 0.000 description 7
239000007800 oxidant agent Substances 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
238000010898 silica gel chromatography Methods 0.000 description 7
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 7
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
150000007513 acids Chemical class 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
239000002775 capsule Substances 0.000 description 6
238000000605 extraction Methods 0.000 description 6
150000004678 hydrides Chemical class 0.000 description 6
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 6
239000000463 material Substances 0.000 description 6
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 6
150000003462 sulfoxides Chemical class 0.000 description 6
125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
230000003115 biocidal effect Effects 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
230000003197 catalytic effect Effects 0.000 description 5
238000002474 experimental method Methods 0.000 description 5
230000007062 hydrolysis Effects 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
229910052763 palladium Inorganic materials 0.000 description 5
150000002960 penicillins Chemical class 0.000 description 5
ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 description 5
239000000843 powder Substances 0.000 description 5
VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 5
238000012360 testing method Methods 0.000 description 5
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 5
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 5
CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 4
229920001817 Agar Polymers 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 4
108090000204 Dipeptidase 1 Proteins 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical class CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
239000012346 acetyl chloride Substances 0.000 description 4
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