SE443980B - Forfarande for framstellning av 2-penem-3-karboxylsyraforeningar - Google Patents

Info

Publication number

SE443980B

SE443980B SE7805217A SE7805217A SE443980B SE 443980 B SE443980 B SE 443980B SE 7805217 A SE7805217 A SE 7805217A SE 7805217 A SE7805217 A SE 7805217A SE 443980 B SE443980 B SE 443980B

Authority

SE

Sweden

Prior art keywords

acid

penem

group

carboxylic acid

lower alkyl

Prior art date

1977-05-09

Links

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• 238000000034 method Methods 0.000 title claims description 34
• DUNKKIRUWZSMPT-RXMQYKEDSA-N (5r)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical class OC(=O)C1=CS[C@@H]2CC(=O)N12 DUNKKIRUWZSMPT-RXMQYKEDSA-N 0.000 title claims description 4
• -1 mercapto, carboxylthio Chemical group 0.000 claims description 321
• 150000001875 compounds Chemical class 0.000 claims description 240
• 125000000217 alkyl group Chemical group 0.000 claims description 93
• 239000000203 mixture Substances 0.000 claims description 79
• 150000003839 salts Chemical class 0.000 claims description 57
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 55
• 125000004432 carbon atom Chemical group C* 0.000 claims description 38
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
• 125000003545 alkoxy group Chemical group 0.000 claims description 34
• 229910052739 hydrogen Inorganic materials 0.000 claims description 26
• 125000004414 alkyl thio group Chemical group 0.000 claims description 23
• 239000001257 hydrogen Substances 0.000 claims description 21
• 229910052736 halogen Inorganic materials 0.000 claims description 20
• 229910052717 sulfur Inorganic materials 0.000 claims description 20
• 150000002367 halogens Chemical class 0.000 claims description 18
• 238000002360 preparation method Methods 0.000 claims description 15
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
• 125000002252 acyl group Chemical group 0.000 claims description 13
• 125000004076 pyridyl group Chemical group 0.000 claims description 13
• 125000002541 furyl group Chemical group 0.000 claims description 12
• 125000001544 thienyl group Chemical group 0.000 claims description 12
• 229910052783 alkali metal Inorganic materials 0.000 claims description 11
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
• 239000001301 oxygen Substances 0.000 claims description 9
• 229910052760 oxygen Inorganic materials 0.000 claims description 9
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
• 239000011593 sulfur Substances 0.000 claims description 9
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
• 125000000524 functional group Chemical group 0.000 claims description 8
• 230000003287 optical effect Effects 0.000 claims description 8
• 125000004423 acyloxy group Chemical group 0.000 claims description 7
• 125000005108 alkenylthio group Chemical group 0.000 claims description 7
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 7
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 7
• 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 7
• 125000003277 amino group Chemical group 0.000 claims description 6
• 230000004962 physiological condition Effects 0.000 claims description 6
• 150000001768 cations Chemical class 0.000 claims description 5
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
• 125000005366 cycloalkylthio group Chemical group 0.000 claims description 4
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 2
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 3
• 125000001589 carboacyl group Chemical group 0.000 claims 2
• DUNKKIRUWZSMPT-UHFFFAOYSA-N 7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CSC2CC(=O)N12 DUNKKIRUWZSMPT-UHFFFAOYSA-N 0.000 claims 1
• 125000005041 acyloxyalkyl group Chemical group 0.000 claims 1
• 125000005055 alkyl alkoxy group Chemical group 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 289
• 239000000243 solution Substances 0.000 description 242
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 146
• OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 128
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 117
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 113
• 238000010521 absorption reaction Methods 0.000 description 110
• 238000002329 infrared spectrum Methods 0.000 description 103
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 97
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 93
• 239000000460 chlorine Substances 0.000 description 91
• 239000002585 base Substances 0.000 description 87
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 80
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 80
• 239000000741 silica gel Substances 0.000 description 77
• 229910002027 silica gel Inorganic materials 0.000 description 77
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 73
• UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical compound OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 72
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 70
• 229910052757 nitrogen Inorganic materials 0.000 description 63
• 239000000706 filtrate Substances 0.000 description 61
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
• 239000011541 reaction mixture Substances 0.000 description 54
• 238000006243 chemical reaction Methods 0.000 description 52
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 51
• 239000002253 acid Substances 0.000 description 50
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
• 229910052938 sodium sulfate Inorganic materials 0.000 description 48
• 235000011152 sodium sulphate Nutrition 0.000 description 48
• 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 44
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 41
• 239000003054 catalyst Substances 0.000 description 41
• 229940093499 ethyl acetate Drugs 0.000 description 39
• 239000012074 organic phase Substances 0.000 description 38
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• 239000002904 solvent Substances 0.000 description 36
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 35
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 35
• 235000017557 sodium bicarbonate Nutrition 0.000 description 35
• 238000013459 approach Methods 0.000 description 34
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 34
• 239000002808 molecular sieve Substances 0.000 description 32
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 32
• QIGBRXMKCJKVMJ-UHFFFAOYSA-N 1,4-Benzenediol Natural products OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 31
• BGUUGGZDHDSUBB-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-ethoxy-2-hydroxyacetate Chemical compound CCOC(O)C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 BGUUGGZDHDSUBB-UHFFFAOYSA-N 0.000 description 30
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 26
• 235000011121 sodium hydroxide Nutrition 0.000 description 26
• 239000007858 starting material Substances 0.000 description 26
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 25
• 125000003118 aryl group Chemical group 0.000 description 23
• 238000002844 melting Methods 0.000 description 23
• 230000008018 melting Effects 0.000 description 23
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
• 150000002148 esters Chemical class 0.000 description 21
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 20
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 19
• 238000001228 spectrum Methods 0.000 description 19
• 238000005406 washing Methods 0.000 description 19
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
• 238000005984 hydrogenation reaction Methods 0.000 description 18
• 230000003197 catalytic effect Effects 0.000 description 17
• 239000005909 Kieselgur Substances 0.000 description 16
• 239000003795 chemical substances by application Substances 0.000 description 16
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 16
• 125000001424 substituent group Chemical group 0.000 description 16
• 238000012546 transfer Methods 0.000 description 16
• 238000002211 ultraviolet spectrum Methods 0.000 description 16
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 15
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
• 239000008346 aqueous phase Substances 0.000 description 14
• 238000000746 purification Methods 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• 239000013078 crystal Substances 0.000 description 12
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
• 125000004043 oxo group Chemical group O=* 0.000 description 12
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 11
• 229960000583 acetic acid Drugs 0.000 description 11
• 230000002378 acidificating effect Effects 0.000 description 11
• 150000007513 acids Chemical class 0.000 description 11
• 239000003638 chemical reducing agent Substances 0.000 description 11
• 239000007788 liquid Substances 0.000 description 11
• 125000001931 aliphatic group Chemical group 0.000 description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
• 150000002431 hydrogen Chemical class 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• 229910052801 chlorine Inorganic materials 0.000 description 9
• NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 9
• 150000002430 hydrocarbons Chemical group 0.000 description 9
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 8
• 150000001340 alkali metals Chemical class 0.000 description 8
• 229910052799 carbon Inorganic materials 0.000 description 8
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• 239000012442 inert solvent Substances 0.000 description 8
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
• 238000001953 recrystallisation Methods 0.000 description 8
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
• 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 7
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical class P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 7
• 150000008064 anhydrides Chemical class 0.000 description 7
• 125000000623 heterocyclic group Chemical group 0.000 description 7
• 229910052725 zinc Inorganic materials 0.000 description 7
• 239000011701 zinc Substances 0.000 description 7
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
• RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 6
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 238000003776 cleavage reaction Methods 0.000 description 6
• 235000019253 formic acid Nutrition 0.000 description 6
• 238000010438 heat treatment Methods 0.000 description 6
• 229910052751 metal Inorganic materials 0.000 description 6
• 239000002184 metal Substances 0.000 description 6
• 244000005700 microbiome Species 0.000 description 6
• 238000006385 ozonation reaction Methods 0.000 description 6
• WURFKUQACINBSI-UHFFFAOYSA-M ozonide Chemical compound [O]O[O-] WURFKUQACINBSI-UHFFFAOYSA-M 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• 230000007017 scission Effects 0.000 description 6
• 235000015424 sodium Nutrition 0.000 description 6
• 159000000000 sodium salts Chemical class 0.000 description 6
• 150000003973 alkyl amines Chemical class 0.000 description 5
• 150000003863 ammonium salts Chemical class 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 230000032050 esterification Effects 0.000 description 5
• 238000005886 esterification reaction Methods 0.000 description 5
• 239000000543 intermediate Substances 0.000 description 5
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
• 230000007935 neutral effect Effects 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
• 239000011877 solvent mixture Substances 0.000 description 5
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 5
• 150000003566 thiocarboxylic acids Chemical class 0.000 description 5
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 4
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
• IOOQOJULHSGTSE-UHFFFAOYSA-N 2-oxopropyl 2-oxoacetate Chemical compound CC(=O)COC(=O)C=O IOOQOJULHSGTSE-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 4
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
• HHLFWLYXYJOTON-UHFFFAOYSA-N Glyoxylic acid Natural products OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 4
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
• 229930195725 Mannitol Natural products 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• 241000589517 Pseudomonas aeruginosa Species 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
• 239000013543 active substance Substances 0.000 description 4
• 125000003342 alkenyl group Chemical group 0.000 description 4
• 125000003302 alkenyloxy group Chemical group 0.000 description 4
• 150000001345 alkine derivatives Chemical class 0.000 description 4
• 150000001412 amines Chemical class 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
• 229910052794 bromium Inorganic materials 0.000 description 4
• 150000001735 carboxylic acids Chemical class 0.000 description 4
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 239000011737 fluorine Substances 0.000 description 4
• 229910052731 fluorine Inorganic materials 0.000 description 4
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
• 150000004678 hydrides Chemical class 0.000 description 4
• 229910000037 hydrogen sulfide Inorganic materials 0.000 description 4
• 238000011065 in-situ storage Methods 0.000 description 4
• 239000011261 inert gas Substances 0.000 description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
• 239000000594 mannitol Substances 0.000 description 4
• 235000010355 mannitol Nutrition 0.000 description 4
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
• 239000012299 nitrogen atmosphere Substances 0.000 description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 description 4
• 230000000269 nucleophilic effect Effects 0.000 description 4
• 125000000962 organic group Chemical group 0.000 description 4
• 230000020477 pH reduction Effects 0.000 description 4
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 4
• 239000000047 product Substances 0.000 description 4
• 238000007363 ring formation reaction Methods 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 125000003396 thiol group Chemical class [H]S* 0.000 description 4
• 239000008096 xylene Substances 0.000 description 4
• NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 3
• MAFXJDMOSOODCM-UHFFFAOYSA-N 2-acetyloxyethanethioic s-acid Chemical compound CC(=O)OCC(O)=S MAFXJDMOSOODCM-UHFFFAOYSA-N 0.000 description 3
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 3
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• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
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• 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
• QSUJAUYJBJRLKV-UHFFFAOYSA-M tetraethylazanium;fluoride Chemical compound [F-].CC[N+](CC)(CC)CC QSUJAUYJBJRLKV-UHFFFAOYSA-M 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
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• BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
• CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
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