DK2940013T3 - HALOGEN-SUBSTITUTED HETEROCYCLIC COMPOUND - Google Patents

Info

Publication number

DK2940013T3

DK2940013T3 DK13868493.1T DK13868493T DK2940013T3 DK 2940013 T3 DK2940013 T3 DK 2940013T3 DK 13868493 T DK13868493 T DK 13868493T DK 2940013 T3 DK2940013 T3 DK 2940013T3

Authority

DK

Denmark

Prior art keywords

biphenyl

amino

carbonyl

ethoxy

thiophen

Prior art date

2012-12-28

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• 150000001875 compounds Chemical class 0.000 claims abstract description 669
• 150000003839 salts Chemical class 0.000 claims abstract description 66
• -1 thiophene compound Chemical class 0.000 claims abstract description 54
• 125000005843 halogen group Chemical group 0.000 claims abstract description 21
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 20
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 14
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 14
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 11
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 11
• 125000003277 amino group Chemical group 0.000 claims abstract description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
• 239000002464 receptor antagonist Substances 0.000 claims abstract description 10
• 229940044551 receptor antagonist Drugs 0.000 claims abstract description 10
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims abstract description 5
• 239000000126 substance Substances 0.000 claims description 256
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 73
• 235000002639 sodium chloride Nutrition 0.000 claims description 68
• YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 65
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 52
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 47
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 42
• 201000010099 disease Diseases 0.000 claims description 18
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
• 206010016654 Fibrosis Diseases 0.000 claims description 10
• 230000004761 fibrosis Effects 0.000 claims description 10
• 206010028980 Neoplasm Diseases 0.000 claims description 9
• 201000011510 cancer Diseases 0.000 claims description 9
• 230000002265 prevention Effects 0.000 claims description 9
• 208000012931 Urologic disease Diseases 0.000 claims description 8
• 230000001900 immune effect Effects 0.000 claims description 8
• 208000026278 immune system disease Diseases 0.000 claims description 8
• 208000027866 inflammatory disease Diseases 0.000 claims description 8
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
• 208000014001 urinary system disease Diseases 0.000 claims description 8
• 102000004137 Lysophosphatidic Acid Receptors Human genes 0.000 claims description 7
• 108090000642 Lysophosphatidic Acid Receptors Proteins 0.000 claims description 7
• MFVVSGGMXMUPTQ-QGZVFWFLSA-N 1-[4-[4-[3-[[(1r)-1-(2-chlorophenyl)ethoxy]carbonylamino]-5-fluorothiophen-2-yl]-2-methoxyphenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound COC1=CC(C2=C(C=C(F)S2)NC(=O)O[C@H](C)C=2C(=CC=CC=2)Cl)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 MFVVSGGMXMUPTQ-QGZVFWFLSA-N 0.000 claims description 5
• MZUQRPNKUOLTDS-MRXNPFEDSA-N 1-[4-[4-[5-chloro-3-[[(1r)-1-(2,5-difluorophenyl)ethoxy]carbonylamino]thiophen-2-yl]-2-methoxyphenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound COC1=CC(C2=C(C=C(Cl)S2)NC(=O)O[C@H](C)C=2C(=CC=C(F)C=2)F)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 MZUQRPNKUOLTDS-MRXNPFEDSA-N 0.000 claims description 5
• 125000005976 1-phenylethyloxy group Chemical group 0.000 claims description 5
• 239000004480 active ingredient Substances 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• GGICMBZLIYWGPX-QGZVFWFLSA-N 1-[4-[4-[3-[[(1r)-1-(2-chlorophenyl)ethoxy]carbonylamino]-5-fluorothiophen-2-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C=C(F)SC=1C(C=C1)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 GGICMBZLIYWGPX-QGZVFWFLSA-N 0.000 claims description 3
• WODIFOKZDINTIN-UHFFFAOYSA-N 1-[4-[4-[5-chloro-3-(1-thiophen-3-ylethoxycarbonylamino)thiophen-2-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound C1=CSC=C1C(C)OC(=O)NC=1C=C(Cl)SC=1C(C=C1)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 WODIFOKZDINTIN-UHFFFAOYSA-N 0.000 claims description 3
• GDHJVUGXDRUDHP-MRXNPFEDSA-N 1-[4-[4-[5-chloro-3-[[(1r)-1-(3,4-difluorophenyl)ethoxy]carbonylamino]thiophen-2-yl]-2-methoxyphenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound COC1=CC(C2=C(C=C(Cl)S2)NC(=O)O[C@H](C)C=2C=C(F)C(F)=CC=2)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 GDHJVUGXDRUDHP-MRXNPFEDSA-N 0.000 claims description 3
• GCKDPEFZAJOXTO-QGZVFWFLSA-N 1-[4-[4-[5-fluoro-3-[[(1r)-1-(2-fluorophenyl)ethoxy]carbonylamino]thiophen-2-yl]-2-methoxyphenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound COC1=CC(C2=C(C=C(F)S2)NC(=O)O[C@H](C)C=2C(=CC=CC=2)F)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 GCKDPEFZAJOXTO-QGZVFWFLSA-N 0.000 claims description 3
• AGCDBAMXYQMEQV-LJQANCHMSA-N 1-[4-[4-[5-fluoro-3-[[(1r)-1-(2-methylphenyl)ethoxy]carbonylamino]thiophen-2-yl]-2-methoxyphenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound COC1=CC(C2=C(C=C(F)S2)NC(=O)O[C@H](C)C=2C(=CC=CC=2)C)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 AGCDBAMXYQMEQV-LJQANCHMSA-N 0.000 claims description 3
• FUPZXYKEQAQSMQ-GOSISDBHSA-N FC1=CC(=C(S1)C1=CC=C(C=C1)C1=CC=C(C=C1)C1(CC1)C(=O)O)NC(=O)O[C@H](C)C1=CC=CC=C1 Chemical compound FC1=CC(=C(S1)C1=CC=C(C=C1)C1=CC=C(C=C1)C1(CC1)C(=O)O)NC(=O)O[C@H](C)C1=CC=CC=C1 FUPZXYKEQAQSMQ-GOSISDBHSA-N 0.000 claims description 3
• QQEFARZLENCSBR-QGZVFWFLSA-N 1-[4-[4-[5-chloro-3-[[(1r)-1-(2-fluorophenyl)ethoxy]carbonylamino]thiophen-2-yl]-2-methoxyphenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound COC1=CC(C2=C(C=C(Cl)S2)NC(=O)O[C@H](C)C=2C(=CC=CC=2)F)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 QQEFARZLENCSBR-QGZVFWFLSA-N 0.000 claims description 2
• LYIMNTCVYUXJEZ-GOSISDBHSA-N 1-[4-[4-[5-chloro-3-[[(1r)-1-phenylethoxy]carbonylamino]thiophen-2-yl]-2-methoxyphenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound COC1=CC(C2=C(C=C(Cl)S2)NC(=O)O[C@H](C)C=2C=CC=CC=2)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 LYIMNTCVYUXJEZ-GOSISDBHSA-N 0.000 claims description 2
• LKUKAHFIQRCGMI-MRXNPFEDSA-N 1-[4-[4-[5-chloro-3-[[(1r)-1-thiophen-2-ylethoxy]carbonylamino]thiophen-2-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound O([C@H](C)C=1SC=CC=1)C(=O)NC=1C=C(Cl)SC=1C(C=C1)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 LKUKAHFIQRCGMI-MRXNPFEDSA-N 0.000 claims description 2
• HOYIQTSPRVGLLZ-UHFFFAOYSA-N 1-[4-[4-[5-fluoro-3-[1-(2-methylthiophen-3-yl)ethoxycarbonylamino]thiophen-2-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound C1=CSC(C)=C1C(C)OC(=O)NC=1C=C(F)SC=1C(C=C1)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 HOYIQTSPRVGLLZ-UHFFFAOYSA-N 0.000 claims description 2
• ZNSZTRXXSKRGJC-UHFFFAOYSA-N 1-[4-[4-[5-fluoro-3-[1-(4-methylthiophen-3-yl)ethoxycarbonylamino]thiophen-2-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound C=1SC=C(C)C=1C(C)OC(=O)NC=1C=C(F)SC=1C(C=C1)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 ZNSZTRXXSKRGJC-UHFFFAOYSA-N 0.000 claims description 2
• FSWUVNCLUBVDLY-QGZVFWFLSA-N 1-[4-[4-[5-fluoro-3-[[(1r)-1-(3-fluorophenyl)ethoxy]carbonylamino]thiophen-2-yl]-2-methoxyphenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound COC1=CC(C2=C(C=C(F)S2)NC(=O)O[C@H](C)C=2C=C(F)C=CC=2)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 FSWUVNCLUBVDLY-QGZVFWFLSA-N 0.000 claims description 2
• MPQWMKUPFUNTPX-MRXNPFEDSA-N 1-[4-[4-[5-fluoro-3-[[(1r)-1-thiophen-3-ylethoxy]carbonylamino]thiophen-2-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound O([C@H](C)C1=CSC=C1)C(=O)NC=1C=C(F)SC=1C(C=C1)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 MPQWMKUPFUNTPX-MRXNPFEDSA-N 0.000 claims description 2
• 230000000144 pharmacologic effect Effects 0.000 claims description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 27
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 3
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 3
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 2
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 1
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 1
• CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims 1
• OYIBXQHGZWLZKY-UHFFFAOYSA-N BrC1=CC(=C(S1)C1=CC=C(C=C1)C1=CC=C(C=C1)C1(CC1)C(=O)O)NC(=O)OC(C)C1=C(C=CC=C1)Cl Chemical compound BrC1=CC(=C(S1)C1=CC=C(C=C1)C1=CC=C(C=C1)C1(CC1)C(=O)O)NC(=O)OC(C)C1=C(C=CC=C1)Cl OYIBXQHGZWLZKY-UHFFFAOYSA-N 0.000 claims 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 1
• AVRWEULSKHQETA-UHFFFAOYSA-N Thiophene-2 Chemical compound S1C=2CCCCCC=2C(C(=O)OC)=C1NC(=O)C1=C(F)C(F)=C(F)C(F)=C1F AVRWEULSKHQETA-UHFFFAOYSA-N 0.000 claims 1
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
• 150000001735 carboxylic acids Chemical class 0.000 claims 1
• 210000003169 central nervous system Anatomy 0.000 claims 1
• 125000001793 isothiazol-3-yl group Chemical group [H]C1=C([H])C(*)=NS1 0.000 claims 1
• CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims 1
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 1
• 210000001428 peripheral nervous system Anatomy 0.000 claims 1
• 239000011780 sodium chloride Substances 0.000 claims 1
• 125000001544 thienyl group Chemical group 0.000 claims 1
• 239000003814 drug Substances 0.000 abstract description 14
• 229930192474 thiophene Natural products 0.000 abstract description 7
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract description 4
• 230000000694 effects Effects 0.000 abstract description 4
• 230000003389 potentiating effect Effects 0.000 abstract description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 693
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 485
• 239000000203 mixture Substances 0.000 description 290
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 231
• 239000000243 solution Substances 0.000 description 227
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 220
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 220
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 208
• 238000006243 chemical reaction Methods 0.000 description 162
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 150
• 239000012044 organic layer Substances 0.000 description 141
• 239000012156 elution solvent Substances 0.000 description 139
• 238000010898 silica gel chromatography Methods 0.000 description 135
• 239000011541 reaction mixture Substances 0.000 description 132
• 238000001819 mass spectrum Methods 0.000 description 131
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 130
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 130
• 239000007787 solid Substances 0.000 description 129
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 113
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 112
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 112
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 81
• 229960004592 isopropanol Drugs 0.000 description 76
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 72
• 239000004305 biphenyl Substances 0.000 description 65
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
• 150000003613 toluenes Chemical class 0.000 description 49
• PEZNEXFPRSOYPL-UHFFFAOYSA-N (bis(trifluoroacetoxy)iodo)benzene Chemical compound FC(F)(F)C(=O)OI(OC(=O)C(F)(F)F)C1=CC=CC=C1 PEZNEXFPRSOYPL-UHFFFAOYSA-N 0.000 description 43
• 239000012300 argon atmosphere Substances 0.000 description 41
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 36
• 238000000034 method Methods 0.000 description 33
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 31
• 239000006260 foam Substances 0.000 description 31
• 238000001914 filtration Methods 0.000 description 29
• 239000007810 chemical reaction solvent Substances 0.000 description 28
• XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 27
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
• 239000010410 layer Substances 0.000 description 27
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
• 239000002253 acid Substances 0.000 description 26
• 239000002585 base Substances 0.000 description 25
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 23
• 239000000460 chlorine Substances 0.000 description 23
• XGRLSUFHELJJAB-JGSYTFBMSA-M sodium;[(2r)-2-hydroxy-3-[(z)-octadec-9-enoyl]oxypropyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)([O-])=O XGRLSUFHELJJAB-JGSYTFBMSA-M 0.000 description 23
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 22
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 22
• 239000012299 nitrogen atmosphere Substances 0.000 description 22
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
• 230000018044 dehydration Effects 0.000 description 21
• 238000006297 dehydration reaction Methods 0.000 description 21
• 150000002081 enamines Chemical class 0.000 description 20
• LDDOSDVZPSGLFZ-UHFFFAOYSA-N ethyl cyclopropanecarboxylate Chemical compound CCOC(=O)C1CC1 LDDOSDVZPSGLFZ-UHFFFAOYSA-N 0.000 description 20
• 125000004494 ethyl ester group Chemical group 0.000 description 20
• MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
• 229910052786 argon Inorganic materials 0.000 description 18
• 239000012298 atmosphere Substances 0.000 description 18
• 235000010290 biphenyl Nutrition 0.000 description 18
• 239000012230 colorless oil Substances 0.000 description 18
• 239000003921 oil Substances 0.000 description 18
• 235000019198 oils Nutrition 0.000 description 18
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• 239000002904 solvent Substances 0.000 description 15
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
• 239000011259 mixed solution Substances 0.000 description 14
• 229910052801 chlorine Inorganic materials 0.000 description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 12
• 239000012046 mixed solvent Substances 0.000 description 12
• 150000002170 ethers Chemical class 0.000 description 11
• 229940052303 ethers for general anesthesia Drugs 0.000 description 11
• 239000000843 powder Substances 0.000 description 11
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 10
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 10
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 10
• 125000001309 chloro group Chemical group Cl* 0.000 description 10
• 239000002808 molecular sieve Substances 0.000 description 10
• 150000003222 pyridines Chemical class 0.000 description 10
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
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• WZGVRXXJKGXOBR-UHFFFAOYSA-N trihexadecyl borate Chemical compound CCCCCCCCCCCCCCCCOB(OCCCCCCCCCCCCCCCC)OCCCCCCCCCCCCCCCC WZGVRXXJKGXOBR-UHFFFAOYSA-N 0.000 description 1
• WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
• NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 210000003708 urethra Anatomy 0.000 description 1
• 239000001993 wax Substances 0.000 description 1