FI78094C

FI78094C - Foerfarande foer framstaellning av antibiotiskt aktiva karbapenemfoereningar.

Foerfarande foer framstaellning av antibiotiskt aktiva karbapenemfoereningar. Download PDF

Info

Publication number: FI78094C
Authority: FI; Finland
Prior art keywords: solution; mmol; compound; methyl; formula
Prior art date: 1982-09-28

Application number

FI833417A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI78094B (fi

FI833417A0 (fi

FI833417A (fi

Inventor

Choung Un Kim

Original Assignee

Bristol Myers Co

Priority date

1982-09-28

Filing date

1983-09-23

Publication date

1989-06-12

1983-09-23 Application filed by Bristol Myers Co filed Critical Bristol Myers Co

1983-09-23 Publication of FI833417A0 publication Critical patent/FI833417A0/fi

1984-03-29 Publication of FI833417A publication Critical patent/FI833417A/fi

1989-02-28 Publication of FI78094B publication Critical patent/FI78094B/fi

1989-06-12 Application granted granted Critical

1989-06-12 Publication of FI78094C publication Critical patent/FI78094C/fi

Links

238000002360 preparation method Methods 0.000 title claims description 45
YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical class C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 title claims description 33
238000000034 method Methods 0.000 title claims description 32
150000001875 compounds Chemical class 0.000 claims description 111
-1 diphenylphosphoryloxy group Chemical group 0.000 claims description 108
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 51
229910052757 nitrogen Inorganic materials 0.000 claims description 36
229910052739 hydrogen Inorganic materials 0.000 claims description 26
125000006239 protecting group Chemical group 0.000 claims description 25
150000003839 salts Chemical class 0.000 claims description 23
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
239000003960 organic solvent Substances 0.000 claims description 17
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 14
229910052799 carbon Inorganic materials 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
150000001450 anions Chemical class 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical compound C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 6
125000000129 anionic group Chemical group 0.000 claims description 6
239000002168 alkylating agent Substances 0.000 claims description 5
229940100198 alkylating agent Drugs 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 5
239000003153 chemical reaction reagent Substances 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000001425 triazolyl group Chemical group 0.000 claims description 5
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 4
125000001072 heteroaryl group Chemical group 0.000 claims description 4
150000002431 hydrogen Chemical group 0.000 claims description 4
239000012442 inert solvent Substances 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
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 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 claims 2
230000008878 coupling Effects 0.000 claims 1
238000010168 coupling process Methods 0.000 claims 1
238000005859 coupling reaction Methods 0.000 claims 1
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 339
239000000243 solution Substances 0.000 description 275
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 247
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 171
239000000203 mixture Substances 0.000 description 151
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 139
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 116
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 101
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 87
239000007787 solid Substances 0.000 description 87
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 81
239000011541 reaction mixture Substances 0.000 description 79
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 75
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 74
238000005481 NMR spectroscopy Methods 0.000 description 65
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 58
239000000047 product Substances 0.000 description 57
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 50
239000002904 solvent Substances 0.000 description 46
239000003921 oil Substances 0.000 description 45
235000019198 oils Nutrition 0.000 description 45
239000000843 powder Substances 0.000 description 44
239000000460 chlorine Substances 0.000 description 43
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
238000004458 analytical method Methods 0.000 description 37
239000012071 phase Substances 0.000 description 37
235000019439 ethyl acetate Nutrition 0.000 description 36
239000000543 intermediate Substances 0.000 description 35
238000001914 filtration Methods 0.000 description 34
239000002244 precipitate Substances 0.000 description 33
239000000706 filtrate Substances 0.000 description 30
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
150000003573 thiols Chemical class 0.000 description 29
FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 description 28
238000007792 addition Methods 0.000 description 28
238000006243 chemical reaction Methods 0.000 description 27
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 25
239000003054 catalyst Substances 0.000 description 24
239000008363 phosphate buffer Substances 0.000 description 22
235000002639 sodium chloride Nutrition 0.000 description 22
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
239000000725 suspension Substances 0.000 description 21
239000012267 brine Substances 0.000 description 20
238000001704 evaporation Methods 0.000 description 20
238000004108 freeze drying Methods 0.000 description 20
OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 20
239000012299 nitrogen atmosphere Substances 0.000 description 20
239000000741 silica gel Substances 0.000 description 20
229910002027 silica gel Inorganic materials 0.000 description 20
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
241000699670 Mus sp. Species 0.000 description 19
230000008020 evaporation Effects 0.000 description 19
230000002441 reversible effect Effects 0.000 description 19
238000003756 stirring Methods 0.000 description 19
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
239000008346 aqueous phase Substances 0.000 description 17
238000004128 high performance liquid chromatography Methods 0.000 description 17
239000003480 eluent Substances 0.000 description 16
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 16
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 16
239000012074 organic phase Substances 0.000 description 16
238000010992 reflux Methods 0.000 description 16
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 16
239000003643 water by type Substances 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
229910000041 hydrogen chloride Inorganic materials 0.000 description 15
ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 description 15
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
238000010521 absorption reaction Methods 0.000 description 14
238000005406 washing Methods 0.000 description 14
241000588724 Escherichia coli Species 0.000 description 13
229930194542 Keto Natural products 0.000 description 13
229910019142 PO4 Inorganic materials 0.000 description 13
238000004587 chromatography analysis Methods 0.000 description 13
125000000468 ketone group Chemical group 0.000 description 13
239000010452 phosphate Substances 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
239000000872 buffer Substances 0.000 description 12
150000007942 carboxylates Chemical class 0.000 description 12
238000000746 purification Methods 0.000 description 12
239000011734 sodium Substances 0.000 description 12
239000000463 material Substances 0.000 description 11
241000588697 Enterobacter cloacae Species 0.000 description 10
239000002253 acid Substances 0.000 description 10
239000013078 crystal Substances 0.000 description 10
150000002148 esters Chemical group 0.000 description 10
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 10
229910052763 palladium Inorganic materials 0.000 description 10
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
150000003952 β-lactams Chemical class 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
WKDDRNSBRWANNC-ATRFCDNQSA-N Thienamycin Chemical compound C1C(SCCN)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 WKDDRNSBRWANNC-ATRFCDNQSA-N 0.000 description 9
239000007864 aqueous solution Substances 0.000 description 9
238000001816 cooling Methods 0.000 description 9
238000010828 elution Methods 0.000 description 9
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 8
239000007853 buffer solution Substances 0.000 description 8
238000004821 distillation Methods 0.000 description 8
230000000694 effects Effects 0.000 description 8
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 8
239000006260 foam Substances 0.000 description 8
238000007918 intramuscular administration Methods 0.000 description 8
229910004298 SiO 2 Inorganic materials 0.000 description 7
238000007796 conventional method Methods 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
229910000402 monopotassium phosphate Inorganic materials 0.000 description 7
235000019796 monopotassium phosphate Nutrition 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
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
238000012546 transfer Methods 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
241000606768 Haemophilus influenzae Species 0.000 description 6
PQBAWAQIRZIWIV-UHFFFAOYSA-N N-methylpyridinium Chemical compound C[N+]1=CC=CC=C1 PQBAWAQIRZIWIV-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
125000002252 acyl group Chemical group 0.000 description 6
239000003242 anti bacterial agent Substances 0.000 description 6
125000003118 aryl group Chemical group 0.000 description 6
210000004369 blood Anatomy 0.000 description 6
239000008280 blood Substances 0.000 description 6
238000010511 deprotection reaction Methods 0.000 description 6
XMYUKSXHYURGOL-UHFFFAOYSA-N ethyl 2-methyltetrazole-5-carboxylate Chemical compound CCOC(=O)C=1N=NN(C)N=1 XMYUKSXHYURGOL-UHFFFAOYSA-N 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
238000005984 hydrogenation reaction Methods 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
238000000338 in vitro Methods 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
239000012280 lithium aluminium hydride Substances 0.000 description 6
MBXNQZHITVCSLJ-UHFFFAOYSA-N methyl fluorosulfonate Chemical compound COS(F)(=O)=O MBXNQZHITVCSLJ-UHFFFAOYSA-N 0.000 description 6
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 description 6
PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
238000005956 quaternization reaction Methods 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
239000007858 starting material Substances 0.000 description 6
239000006188 syrup Substances 0.000 description 6
235000020357 syrup Nutrition 0.000 description 6
238000011282 treatment Methods 0.000 description 6
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 6
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 5
239000005909 Kieselgur Substances 0.000 description 5
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
230000000844 anti-bacterial effect Effects 0.000 description 5
229940126214 compound 3 Drugs 0.000 description 5
239000013058 crude material Substances 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 5
239000008055 phosphate buffer solution Substances 0.000 description 5
210000002966 serum Anatomy 0.000 description 5
125000000446 sulfanediyl group Chemical group *S* 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
WEDKTMOIKOKBSH-UHFFFAOYSA-N 4,5-dihydrothiadiazole Chemical compound C1CN=NS1 WEDKTMOIKOKBSH-UHFFFAOYSA-N 0.000 description 4
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
206010035664 Pneumonia Diseases 0.000 description 4
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
OATSQCXMYKYFQO-UHFFFAOYSA-N S-methyl thioacetate Chemical compound CSC(C)=O OATSQCXMYKYFQO-UHFFFAOYSA-N 0.000 description 4
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FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 4
XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 4
230000003115 biocidal effect Effects 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 4
239000000284 extract Substances 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
239000005457 ice water Substances 0.000 description 4
239000012535 impurity Substances 0.000 description 4
239000010410 layer Substances 0.000 description 4
229910052700 potassium Inorganic materials 0.000 description 4
239000011591 potassium Substances 0.000 description 4
SJIIDWBFRZACDQ-UHFFFAOYSA-N pyridin-2-ylmethanethiol Chemical compound SCC1=CC=CC=N1 SJIIDWBFRZACDQ-UHFFFAOYSA-N 0.000 description 4
238000006722 reduction reaction Methods 0.000 description 4
239000011347 resin Substances 0.000 description 4
229920005989 resin Polymers 0.000 description 4
239000000126 substance Substances 0.000 description 4
DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 4
MWWCRZWOTAOLEX-UHFFFAOYSA-N (3-methylpyridin-4-yl)methanol Chemical compound CC1=CN=CC=C1CO MWWCRZWOTAOLEX-UHFFFAOYSA-N 0.000 description 3
RNYSYSXUCVOYRH-UHFFFAOYSA-N 3-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1C(C)=C(C(O)=O)N2C(=O)CC21 RNYSYSXUCVOYRH-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
241000194032 Enterococcus faecalis Species 0.000 description 3
239000012359 Methanesulfonyl chloride Substances 0.000 description 3
244000038458 Nepenthes mirabilis Species 0.000 description 3
PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
229940041011 carbapenems Drugs 0.000 description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
150000001805 chlorine compounds Chemical class 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
229940125904 compound 1 Drugs 0.000 description 3
229940125782 compound 2 Drugs 0.000 description 3
229940125898 compound 5 Drugs 0.000 description 3
239000012043 crude product Substances 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
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