SK283413B6 - 2-Tioindoly, 2-indolíntióny a polysulfidy, ich selénové analógy a farmaceutické prostriedky na ich báze - Google Patents

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Publication number

SK283413B6

SK283413B6 SK135-95A SK13595A SK283413B6 SK 283413 B6 SK283413 B6 SK 283413B6 SK 13595 A SK13595 A SK 13595A SK 283413 B6 SK283413 B6 SK 283413B6

Authority

SK

Slovakia

Prior art keywords

methyl

formula

bis

disulfide

arh

Prior art date

1992-08-06

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• 239000005077 polysulfide Substances 0.000 title claims abstract description 35
• 229920001021 polysulfide Polymers 0.000 title claims abstract description 35
• 150000008117 polysulfides Polymers 0.000 title claims abstract description 35
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
• IGJWTYFTQNHSEK-UHFFFAOYSA-N 1,3-dihydroindole-2-thione Chemical class C1=CC=C2NC(=S)CC2=C1 IGJWTYFTQNHSEK-UHFFFAOYSA-N 0.000 title claims abstract description 10
• 150000003346 selenoethers Chemical class 0.000 title description 3
• IWPFCVWNSWZZFA-UHFFFAOYSA-N C1=CC=C2NC(=[Se])CC2=C1 Chemical compound C1=CC=C2NC(=[Se])CC2=C1 IWPFCVWNSWZZFA-UHFFFAOYSA-N 0.000 title description 2
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 404
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 157
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 87
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims abstract description 73
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 54
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 52
• 150000003839 salts Chemical class 0.000 claims abstract description 36
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 32
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 27
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims abstract description 26
• 229930192474 thiophene Natural products 0.000 claims abstract description 26
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 24
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 24
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
• 125000004122 cyclic group Chemical group 0.000 claims abstract description 11
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
• 150000002367 halogens Chemical class 0.000 claims abstract description 8
• 125000001424 substituent group Chemical group 0.000 claims abstract description 7
• BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical class [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims abstract description 4
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract 13
• 150000001875 compounds Chemical class 0.000 claims description 628
• 239000001257 hydrogen Substances 0.000 claims description 255
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 218
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 191
• 150000002431 hydrogen Chemical group 0.000 claims description 142
• 229910052799 carbon Inorganic materials 0.000 claims description 116
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 102
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 98
• -1 cyclic radical Chemical class 0.000 claims description 70
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 56
• OTYIADUBGFZFSV-UHFFFAOYSA-N n-[4-(acetylsulfamoyl)phenyl]-2-[[2-[[4-(acetylsulfamoyl)phenyl]carbamoyl]phenyl]disulfanyl]benzamide Chemical compound C1=CC(S(=O)(=O)NC(=O)C)=CC=C1NC(=O)C1=CC=CC=C1SSC1=CC=CC=C1C(=O)NC1=CC=C(S(=O)(=O)NC(C)=O)C=C1 OTYIADUBGFZFSV-UHFFFAOYSA-N 0.000 claims description 32
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
• 150000003254 radicals Chemical class 0.000 claims description 15
• 239000011669 selenium Substances 0.000 claims description 11
• 230000001419 dependent effect Effects 0.000 claims description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 6
• 230000010261 cell growth Effects 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 150000003342 selenium Chemical class 0.000 claims description 6
• 241000124008 Mammalia Species 0.000 claims description 5
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 5
• 125000002883 imidazolyl group Chemical group 0.000 claims description 5
• HVRCLXXJIQTXHC-UHFFFAOYSA-N 1-methylindole-3-carboxylic acid Chemical compound C1=CC=C2N(C)C=C(C(O)=O)C2=C1 HVRCLXXJIQTXHC-UHFFFAOYSA-N 0.000 claims description 4
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
• KTIODNZPIYCZSR-UHFFFAOYSA-N 2-(2-sulfanylidene-1,3-dihydroindol-3-yl)acetic acid Chemical compound C1=CC=C2C(CC(=O)O)C(=S)NC2=C1 KTIODNZPIYCZSR-UHFFFAOYSA-N 0.000 claims description 3
• HNEORRPIDMAPCB-UHFFFAOYSA-N 2-[(3-carboxy-1-methylindol-2-yl)diselanyl]-1-methylindole-3-carboxylic acid Chemical compound C1=CC=C2N(C)C([Se][Se]C=3N(C4=CC=CC=C4C=3C(O)=O)C)=C(C(O)=O)C2=C1 HNEORRPIDMAPCB-UHFFFAOYSA-N 0.000 claims description 3
• XZFPVQIMSWHDCR-UHFFFAOYSA-N 3-(2-sulfanylidene-1,3-dihydroindol-3-yl)propanoic acid Chemical compound C1=CC=C2C(CCC(=O)O)C(=S)NC2=C1 XZFPVQIMSWHDCR-UHFFFAOYSA-N 0.000 claims description 3
• XMTNWZBWWSPDPN-UHFFFAOYSA-N 3-butyl-1,5-dimethyl-3H-indole-2-thione Chemical compound C1=C(C)C=C2C(CCCC)C(=S)N(C)C2=C1 XMTNWZBWWSPDPN-UHFFFAOYSA-N 0.000 claims description 3
• HGQLOUYLTRSJRA-UHFFFAOYSA-N 3-butyl-2-[(3-butyl-1-methylindol-2-yl)disulfanyl]-1-methylindole Chemical compound CN1C2=CC=CC=C2C(CCCC)=C1SSC1=C(CCCC)C2=CC=CC=C2N1C HGQLOUYLTRSJRA-UHFFFAOYSA-N 0.000 claims description 3
• JRCARFUVXOJUCM-UHFFFAOYSA-N C1=CC=C2C(CCCC)C(=S)N(C)C2=C1 Chemical compound C1=CC=C2C(CCCC)C(=S)N(C)C2=C1 JRCARFUVXOJUCM-UHFFFAOYSA-N 0.000 claims description 3
• KKTAXCWCKSLCHF-UHFFFAOYSA-N n,1-dimethyl-2-[[1-methyl-3-(methylcarbamoyl)indol-2-yl]diselanyl]indole-3-carboxamide Chemical compound CN1C2=CC=CC=C2C(C(=O)NC)=C1[Se][Se]C1=C(C(=O)NC)C2=CC=CC=C2N1C KKTAXCWCKSLCHF-UHFFFAOYSA-N 0.000 claims description 3
• PMQPQXPWWRMDGF-UHFFFAOYSA-N 1-methyl-n-phenyl-2-sulfanylidene-3h-indole-3-carboxamide Chemical compound C12=CC=CC=C2N(C)C(=S)C1C(=O)NC1=CC=CC=C1 PMQPQXPWWRMDGF-UHFFFAOYSA-N 0.000 claims description 2
• MGQMNRPORBTSDW-UHFFFAOYSA-N 2-(1-methyl-2-sulfanylidene-3h-indol-3-yl)acetic acid Chemical compound C1=CC=C2N(C)C(=S)C(CC(O)=O)C2=C1 MGQMNRPORBTSDW-UHFFFAOYSA-N 0.000 claims description 2
• KUXZZVWLUDGVFK-UHFFFAOYSA-N 2-[[1-carboxy-1-(1-methylindol-3-yl)ethyl]disulfanyl]-2-(1-methylindol-3-yl)propanoic acid Chemical compound C1=CC=C2C(C(C)(C(O)=O)SSC(C)(C3=CN(C4=CC=CC=C43)C)C(O)=O)=CN(C)C2=C1 KUXZZVWLUDGVFK-UHFFFAOYSA-N 0.000 claims description 2
• YNAIRLXDPHCRHZ-UHFFFAOYSA-N 2-[[1-carboxy-2-(1-methylindol-3-yl)ethyl]disulfanyl]-3-(1-methylindol-3-yl)propanoic acid Chemical compound C12=CC=CC=C2N(C)C=C1CC(C(O)=O)SSC(C(O)=O)CC1=CN(C)C2=CC=CC=C12 YNAIRLXDPHCRHZ-UHFFFAOYSA-N 0.000 claims description 2
• LBALNCFWTZTSFW-UHFFFAOYSA-N 3-(1-methyl-2-sulfanylidene-3h-indol-3-yl)propanoic acid Chemical compound C1=CC=C2N(C)C(=S)C(CCC(O)=O)C2=C1 LBALNCFWTZTSFW-UHFFFAOYSA-N 0.000 claims description 2
• QHJCJUXULVYEKC-UHFFFAOYSA-N 4-(1-methyl-2-sulfanylidene-3h-indol-3-yl)butanoic acid Chemical compound C1=CC=C2N(C)C(=S)C(CCCC(O)=O)C2=C1 QHJCJUXULVYEKC-UHFFFAOYSA-N 0.000 claims description 2
• HDSHPZKIYJXQSA-UHFFFAOYSA-N 4-(1-methyl-2-sulfanylidene-3h-indole-3-carbonyl)benzoic acid Chemical compound C12=CC=CC=C2N(C)C(=S)C1C(=O)C1=CC=C(C(O)=O)C=C1 HDSHPZKIYJXQSA-UHFFFAOYSA-N 0.000 claims description 2
• 230000001594 aberrant effect Effects 0.000 claims description 2
• MMQRRPCTOSYLTB-UHFFFAOYSA-N n-benzyl-2-[[1-(benzylamino)-3-(1h-indol-3-yl)-1-oxopropan-2-yl]disulfanyl]-3-(1h-indol-3-yl)propanamide Chemical compound C=1NC2=CC=CC=C2C=1CC(SSC(CC=1C2=CC=CC=C2NC=1)C(=O)NCC=1C=CC=CC=1)C(=O)NCC1=CC=CC=C1 MMQRRPCTOSYLTB-UHFFFAOYSA-N 0.000 claims description 2
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical group CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 4
• RHQWHANZNHLOIO-UHFFFAOYSA-N 1-[2-(diethylamino)ethyl]-2-[[1-[2-(diethylamino)ethyl]-3-(methylcarbamoyl)indol-2-yl]diselanyl]-n-methylindole-3-carboxamide Chemical compound C1=CC=C2N(CCN(CC)CC)C([Se][Se]C=3N(C4=CC=CC=C4C=3C(=O)NC)CCN(CC)CC)=C(C(=O)NC)C2=C1 RHQWHANZNHLOIO-UHFFFAOYSA-N 0.000 claims 2
• XQPHLDWWTAAPNR-UHFFFAOYSA-N CN1C(=C(C2=CC=CC=C12)S(=O)(=O)C1=CC=CC=C1)SSC=1N(C2=CC=CC=C2C1S(=O)(=O)C1=CC=CC=C1)C Chemical compound CN1C(=C(C2=CC=CC=C12)S(=O)(=O)C1=CC=CC=C1)SSC=1N(C2=CC=CC=C2C1S(=O)(=O)C1=CC=CC=C1)C XQPHLDWWTAAPNR-UHFFFAOYSA-N 0.000 claims 2
• ZKIIIDMIMRJWPR-UHFFFAOYSA-N N-benzyl-N-(2-sulfanylidene-1,3-dihydroindol-3-yl)acetamide Chemical compound CC(=O)N(Cc1ccccc1)C1C(=S)Nc2ccccc12 ZKIIIDMIMRJWPR-UHFFFAOYSA-N 0.000 claims 2
• 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims 2
• DWORZCJMOCMSFP-UHFFFAOYSA-N methyl 2-(2-methylsulfanyl-1h-indol-3-yl)acetate Chemical compound C1=CC=C2C(CC(=O)OC)=C(SC)NC2=C1 DWORZCJMOCMSFP-UHFFFAOYSA-N 0.000 claims 2
• PJKWAKAPBOGIKH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-2-[[3-[2-(diethylamino)ethyl-methylcarbamoyl]-1h-indol-2-yl]diselanyl]-n-methyl-1h-indole-3-carboxamide Chemical compound N1C2=CC=CC=C2C(C(=O)N(C)CCN(CC)CC)=C1[Se][Se]C1=C(C(=O)N(C)CCN(CC)CC)C2=CC=CC=C2N1 PJKWAKAPBOGIKH-UHFFFAOYSA-N 0.000 claims 2
• XZTHVVIRCUVGRE-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-2-[[3-[2-(diethylamino)ethylcarbamoyl]-1-methylindol-2-yl]diselanyl]-1-methylindole-3-carboxamide Chemical compound CN1C2=CC=CC=C2C(C(=O)NCCN(CC)CC)=C1[Se][Se]C1=C(C(=O)NCCN(CC)CC)C2=CC=CC=C2N1C XZTHVVIRCUVGRE-UHFFFAOYSA-N 0.000 claims 2
• DOBDKFHLOMDQHB-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-2-[[3-[2-(diethylamino)ethylcarbamoyl]-1h-indol-2-yl]diselanyl]-1h-indole-3-carboxamide Chemical compound N1C2=CC=CC=C2C(C(=O)NCCN(CC)CC)=C1[Se][Se]C1=C(C(=O)NCCN(CC)CC)C2=CC=CC=C2N1 DOBDKFHLOMDQHB-UHFFFAOYSA-N 0.000 claims 2
• LNRQRRCDPILCSE-UHFFFAOYSA-N 1-methyl-2-methylsulfanyl-n-phenyl-2,3-dihydroindole-3-carboxamide Chemical compound C12=CC=CC=C2N(C)C(SC)C1C(=O)NC1=CC=CC=C1 LNRQRRCDPILCSE-UHFFFAOYSA-N 0.000 claims 1
• SUTIISXRTZTQML-UHFFFAOYSA-N 2-[[1-carboxy-3-(1-methylindol-3-yl)propyl]disulfanyl]-4-(1-methylindol-3-yl)butanoic acid Chemical compound C12=CC=CC=C2N(C)C=C1CCC(C(O)=O)SSC(C(O)=O)CCC1=CN(C)C2=CC=CC=C12 SUTIISXRTZTQML-UHFFFAOYSA-N 0.000 claims 1
• HHPDUGVXIBPIEG-UHFFFAOYSA-N 2-[[2-carboxy-1-(1-methylindol-3-yl)propan-2-yl]disulfanyl]-2-methyl-3-(1-methylindol-3-yl)propanoic acid Chemical compound C12=CC=CC=C2N(C)C=C1CC(C)(C(O)=O)SSC(C)(C(O)=O)CC1=CN(C)C2=CC=CC=C12 HHPDUGVXIBPIEG-UHFFFAOYSA-N 0.000 claims 1
• OKZLZNFBUWVBMP-UHFFFAOYSA-N 4-(2-sulfanylidene-1,3-dihydroindol-3-yl)butanoic acid Chemical compound C1=CC=C2C(CCCC(=O)O)C(=S)NC2=C1 OKZLZNFBUWVBMP-UHFFFAOYSA-N 0.000 claims 1
• XFLYPZYKOUEZGL-UHFFFAOYSA-N methyl 4-(1-methyl-2-sulfanylidene-3h-indole-3-carbonyl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(=O)C1C2=CC=CC=C2N(C)C1=S XFLYPZYKOUEZGL-UHFFFAOYSA-N 0.000 claims 1
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims 1
• YABONUOGDVBUJI-UHFFFAOYSA-N n-benzyl-2-[[2-(benzylamino)-1-(1h-indol-3-yl)-2-oxoethyl]disulfanyl]-2-(1h-indol-3-yl)acetamide Chemical compound C=1C=CC=CC=1CNC(=O)C(C=1C2=CC=CC=C2NC=1)SSC(C=1C2=CC=CC=C2NC=1)C(=O)NCC1=CC=CC=C1 YABONUOGDVBUJI-UHFFFAOYSA-N 0.000 claims 1
• SSIOMHJBYZEOEK-UHFFFAOYSA-N n-methyl-2-[[3-(methylcarbamoyl)-1h-indol-2-yl]diselanyl]-1h-indole-3-carboxamide Chemical compound N1C2=CC=CC=C2C(C(=O)NC)=C1[Se][Se]C1=C(C(=O)NC)C2=CC=CC=C2N1 SSIOMHJBYZEOEK-UHFFFAOYSA-N 0.000 claims 1
• 235000019260 propionic acid Nutrition 0.000 claims 1
• 229910052711 selenium Inorganic materials 0.000 claims 1
• 125000000217 alkyl group Chemical group 0.000 abstract description 15
• 239000003112 inhibitor Substances 0.000 abstract description 8
• 239000000654 additive Substances 0.000 abstract 1
• 230000000996 additive effect Effects 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 414
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 351
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 268
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 216
• 239000000203 mixture Substances 0.000 description 185
• 238000004458 analytical method Methods 0.000 description 160
• 239000000243 solution Substances 0.000 description 156
• 239000003208 petroleum Substances 0.000 description 126
• 229910052757 nitrogen Inorganic materials 0.000 description 122
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 111
• 238000004519 manufacturing process Methods 0.000 description 90
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
• 239000003921 oil Substances 0.000 description 82
• 235000019198 oils Nutrition 0.000 description 82
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 81
• 229910052717 sulfur Inorganic materials 0.000 description 79
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
• 238000002425 crystallisation Methods 0.000 description 76
• 230000008025 crystallization Effects 0.000 description 73
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 72
• 239000000741 silica gel Substances 0.000 description 69
• 229910002027 silica gel Inorganic materials 0.000 description 69
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 67
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 54
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 52
• 239000007787 solid Substances 0.000 description 52
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 50
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
• 238000006243 chemical reaction Methods 0.000 description 42
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 40
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
• 239000000047 product Substances 0.000 description 39
• 239000002904 solvent Substances 0.000 description 38
• 239000012279 sodium borohydride Substances 0.000 description 36
• 229910000033 sodium borohydride Inorganic materials 0.000 description 36
• 239000000284 extract Substances 0.000 description 31
• 238000002844 melting Methods 0.000 description 31
• 230000008018 melting Effects 0.000 description 31
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
• 239000000725 suspension Substances 0.000 description 29
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
• 238000010828 elution Methods 0.000 description 26
• 239000000463 material Substances 0.000 description 25
• 239000011541 reaction mixture Substances 0.000 description 25
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
• DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 24
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 24
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 23
• 239000000460 chlorine Substances 0.000 description 22
• FNGLQNMQHOAIJQ-UHFFFAOYSA-N Cl[S](Cl)Cl Chemical compound Cl[S](Cl)Cl FNGLQNMQHOAIJQ-UHFFFAOYSA-N 0.000 description 21
• KQHGHZZWMCVHEY-UHFFFAOYSA-M lithium;methanethiolate Chemical compound [Li+].[S-]C KQHGHZZWMCVHEY-UHFFFAOYSA-M 0.000 description 20
• 239000003480 eluent Substances 0.000 description 19
• CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 19
• GOLXRNDWAUTYKT-UHFFFAOYSA-N 3-(1H-indol-3-yl)propanoic acid Chemical compound C1=CC=C2C(CCC(=O)O)=CNC2=C1 GOLXRNDWAUTYKT-UHFFFAOYSA-N 0.000 description 18
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
• 229960000583 acetic acid Drugs 0.000 description 17
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
• 229960001701 chloroform Drugs 0.000 description 16
• 238000000034 method Methods 0.000 description 15
• 238000003756 stirring Methods 0.000 description 15
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
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