FI77446C - Foerfarande foer framstaellning av psykoterapeutiskt anvaendbara 1-fenyl-2(1h,3h)-indoloner. - Google Patents
Foerfarande foer framstaellning av psykoterapeutiskt anvaendbara 1-fenyl-2(1h,3h)-indoloner. Download PDFInfo
- Publication number
- FI77446C FI77446C FI833335A FI833335A FI77446C FI 77446 C FI77446 C FI 77446C FI 833335 A FI833335 A FI 833335A FI 833335 A FI833335 A FI 833335A FI 77446 C FI77446 C FI 77446C
- Authority
- FI
- Finland
- Prior art keywords
- formula
- indolone
- phenyl
- compound
- reaction
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 74
- -1 1,3-propylene, 1,4- butylene Chemical group 0.000 claims description 79
- 150000001875 compounds Chemical class 0.000 claims description 62
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- 239000000203 mixture Substances 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 38
- 239000000460 chlorine Chemical group 0.000 claims description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 238000002360 preparation method Methods 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 239000012442 inert solvent Substances 0.000 claims description 14
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 12
- OWPNVXATCSXTBK-UHFFFAOYSA-N 1-phenyl-3h-indol-2-one Chemical class O=C1CC2=CC=CC=C2N1C1=CC=CC=C1 OWPNVXATCSXTBK-UHFFFAOYSA-N 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 11
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 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 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- FGFUBBNNYLNVLJ-UHFFFAOYSA-N indolone Natural products C1=CC=C2C(=O)C=NC2=C1 FGFUBBNNYLNVLJ-UHFFFAOYSA-N 0.000 claims description 10
- 150000001408 amides Chemical class 0.000 claims description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 229910052731 fluorine Chemical group 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 239000011737 fluorine Chemical group 0.000 claims description 5
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 4
- 238000005804 alkylation reaction Methods 0.000 claims description 4
- 229910052794 bromium Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 150000003857 carboxamides Chemical class 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 239000003701 inert diluent Substances 0.000 claims description 3
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 239000012429 reaction media Substances 0.000 claims 2
- RYXPMWYHEBGTRV-UHFFFAOYSA-N Omeprazole sodium Chemical compound [Na+].N=1C2=CC(OC)=CC=C2[N-]C=1S(=O)CC1=NC=C(C)C(OC)=C1C RYXPMWYHEBGTRV-UHFFFAOYSA-N 0.000 claims 1
- 150000001449 anionic compounds Chemical class 0.000 claims 1
- 125000000129 anionic group Chemical group 0.000 claims 1
- LFKYBJLFJOOKAE-UHFFFAOYSA-N imidazol-2-ylidenemethanone Chemical compound O=C=C1N=CC=N1 LFKYBJLFJOOKAE-UHFFFAOYSA-N 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 210000005036 nerve Anatomy 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 4
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- XRKBWYMXJJLQTN-UHFFFAOYSA-N 1-phenyl-3-pyrrolidin-2-ylideneindol-2-one Chemical class O=C1N(C=2C=CC=CC=2)C2=CC=CC=C2C1=C1CCCN1 XRKBWYMXJJLQTN-UHFFFAOYSA-N 0.000 abstract 1
- 208000019901 Anxiety disease Diseases 0.000 abstract 1
- 230000036506 anxiety Effects 0.000 abstract 1
- 206010015037 epilepsy Diseases 0.000 abstract 1
- 239000003445 gaba agent Substances 0.000 abstract 1
- 239000003176 neuroleptic agent Substances 0.000 abstract 1
- 201000000980 schizophrenia Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 205
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 108
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 93
- 239000000047 product Substances 0.000 description 77
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 53
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 41
- 238000004587 chromatography analysis Methods 0.000 description 37
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 239000003480 eluent Substances 0.000 description 20
- GRHZRAGCCPFBLA-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1h-indol-2-one Chemical compound C1=CC=C2C(=CN(C)C)C(=O)NC2=C1 GRHZRAGCCPFBLA-UHFFFAOYSA-N 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical class C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000007787 solid Substances 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 238000001953 recrystallisation Methods 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 11
- 238000002425 crystallisation Methods 0.000 description 11
- 230000008025 crystallization Effects 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- HMWMGKFMLJFUJI-UHFFFAOYSA-N 1-(3-chlorophenyl)-3h-indol-2-one Chemical compound ClC1=CC=CC(N2C3=CC=CC=C3CC2=O)=C1 HMWMGKFMLJFUJI-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- JMLWXCJXOYDXRN-UHFFFAOYSA-N 1-chloro-3-iodobenzene Chemical compound ClC1=CC=CC(I)=C1 JMLWXCJXOYDXRN-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical class C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- FBZVZUSVGKOWHG-UHFFFAOYSA-N 1,1-dimethoxy-n,n-dimethylethanamine Chemical compound COC(C)(OC)N(C)C FBZVZUSVGKOWHG-UHFFFAOYSA-N 0.000 description 4
- XOSTYPSDUQZJEY-UHFFFAOYSA-N 6-chloro-1-phenyl-3h-indol-2-one Chemical compound C12=CC(Cl)=CC=C2CC(=O)N1C1=CC=CC=C1 XOSTYPSDUQZJEY-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical group BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical class ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- GKDLYVYEIVOSKS-UHFFFAOYSA-N 1-(3-chloro-4-methoxyphenyl)-3h-indol-2-one Chemical compound C1=C(Cl)C(OC)=CC=C1N1C2=CC=CC=C2CC1=O GKDLYVYEIVOSKS-UHFFFAOYSA-N 0.000 description 3
- IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 3
- OZZVVICMSONJND-UHFFFAOYSA-N 3-(1-methylpyrrolidin-2-ylidene)-1h-indol-2-one Chemical compound CN1CCCC1=C1C2=CC=CC=C2NC1=O OZZVVICMSONJND-UHFFFAOYSA-N 0.000 description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 3
- 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 3
- DWNXGZBXFDNKOR-UHFFFAOYSA-N 4-bromo-2-fluoro-1-methoxybenzene Chemical compound COC1=CC=C(Br)C=C1F DWNXGZBXFDNKOR-UHFFFAOYSA-N 0.000 description 3
- QJPJQTDYNZXKQF-UHFFFAOYSA-N 4-bromoanisole Chemical compound COC1=CC=C(Br)C=C1 QJPJQTDYNZXKQF-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical group CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- IORXXINRTWZAFJ-UHFFFAOYSA-N 1-(3-chloro-4-methoxyphenyl)-3-(dimethylaminomethylidene)indol-2-one Chemical compound C1=C(Cl)C(OC)=CC=C1N1C2=CC=CC=C2C(=CN(C)C)C1=O IORXXINRTWZAFJ-UHFFFAOYSA-N 0.000 description 2
- KXJVTAYYLZXPEP-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(hydroxymethylidene)indol-2-one Chemical compound C12=CC=CC=C2C(=CO)C(=O)N1C1=CC=CC(Cl)=C1 KXJVTAYYLZXPEP-UHFFFAOYSA-N 0.000 description 2
- OALXBYKHGNKGOC-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(morpholin-4-ylmethylidene)indol-2-one Chemical compound ClC1=CC=CC(N2C3=CC=CC=C3C(=CN3CCOCC3)C2=O)=C1 OALXBYKHGNKGOC-UHFFFAOYSA-N 0.000 description 2
- SWYXNBDQKWYUHA-UHFFFAOYSA-N 1-(3-fluorophenyl)-3h-indol-2-one Chemical compound FC1=CC=CC(N2C3=CC=CC=C3CC2=O)=C1 SWYXNBDQKWYUHA-UHFFFAOYSA-N 0.000 description 2
- UZZNUBBBIPNJQU-UHFFFAOYSA-N 1-(4-methoxyphenyl)-3h-indol-2-one Chemical compound C1=CC(OC)=CC=C1N1C2=CC=CC=C2CC1=O UZZNUBBBIPNJQU-UHFFFAOYSA-N 0.000 description 2
- CJJDJQFZVLGJLB-UHFFFAOYSA-N 1-(4-methoxyphenyl)indole Chemical compound C1=CC(OC)=CC=C1N1C2=CC=CC=C2C=C1 CJJDJQFZVLGJLB-UHFFFAOYSA-N 0.000 description 2
- ZDFBKZUDCQQKAC-UHFFFAOYSA-N 1-bromo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1 ZDFBKZUDCQQKAC-UHFFFAOYSA-N 0.000 description 2
- PDLMHPLPFRWTMN-UHFFFAOYSA-N 3-(azepan-2-ylidene)-1-(3-chlorophenyl)indol-2-one Chemical compound ClC1=CC=CC(N2C3=CC=CC=C3C(C2=O)=C2NCCCCC2)=C1 PDLMHPLPFRWTMN-UHFFFAOYSA-N 0.000 description 2
- AKXNFZXWGSXTSI-UHFFFAOYSA-N 3-(hydroxymethylidene)-1-phenylindol-2-one Chemical compound C12=CC=CC=C2C(=CO)C(=O)N1C1=CC=CC=C1 AKXNFZXWGSXTSI-UHFFFAOYSA-N 0.000 description 2
- DVZTYGJWLTYBNZ-UHFFFAOYSA-N 3-[3-(1-methylpyrrolidin-2-ylidene)-2-oxoindol-1-yl]benzonitrile Chemical compound CN1CCCC1=C1C2=CC=CC=C2N(C=2C=C(C=CC=2)C#N)C1=O DVZTYGJWLTYBNZ-UHFFFAOYSA-N 0.000 description 2
- STXAVEHFKAXGOX-UHFFFAOYSA-N 3-bromobenzonitrile Chemical group BrC1=CC=CC(C#N)=C1 STXAVEHFKAXGOX-UHFFFAOYSA-N 0.000 description 2
- FIWAJICRUSLRCT-UHFFFAOYSA-N 4-chloro-3-(dimethylaminomethylidene)-1h-indol-2-one Chemical compound C1=CC(Cl)=C2C(=CN(C)C)C(=O)NC2=C1 FIWAJICRUSLRCT-UHFFFAOYSA-N 0.000 description 2
- SGJCXOWLBVNALR-UHFFFAOYSA-N 4-fluoro-n-(4-fluorophenyl)aniline Chemical compound C1=CC(F)=CC=C1NC1=CC=C(F)C=C1 SGJCXOWLBVNALR-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- PNDRDNIFVDEDDI-UHFFFAOYSA-N 5-ethoxy-3,4-dihydro-2h-pyrrole Chemical compound CCOC1=NCCC1 PNDRDNIFVDEDDI-UHFFFAOYSA-N 0.000 description 2
- KEKYGJOXOIYUHD-UHFFFAOYSA-N 5-fluoro-1-(4-fluorophenyl)-3h-indol-2-one Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(F)C=C2CC1=O KEKYGJOXOIYUHD-UHFFFAOYSA-N 0.000 description 2
- CENVPIZOTHULGJ-UHFFFAOYSA-N 6-chloro-1,3-dihydroindol-2-one Chemical compound ClC1=CC=C2CC(=O)NC2=C1 CENVPIZOTHULGJ-UHFFFAOYSA-N 0.000 description 2
- TUSNHEWVQIGUMS-UHFFFAOYSA-N 6-fluoro-1-phenyl-3h-indol-2-one Chemical compound C12=CC(F)=CC=C2CC(=O)N1C1=CC=CC=C1 TUSNHEWVQIGUMS-UHFFFAOYSA-N 0.000 description 2
- DNXIQMQGKSQHPC-UHFFFAOYSA-N 7-methoxy-3,4,5,6-tetrahydro-2h-azepine Chemical compound COC1=NCCCCC1 DNXIQMQGKSQHPC-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- FVIGODVHAVLZOO-UHFFFAOYSA-N Dixanthogen Chemical compound CCOC(=S)SSC(=S)OCC FVIGODVHAVLZOO-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000006254 arylation reaction Methods 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 150000005624 indolones Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 239000004533 oil dispersion Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910052701 rubidium Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- NADPFZNWCQIJJW-UHFFFAOYSA-N 1,2-dichloro-4-iodobenzene Chemical compound ClC1=CC=C(I)C=C1Cl NADPFZNWCQIJJW-UHFFFAOYSA-N 0.000 description 1
- JSRLURSZEMLAFO-UHFFFAOYSA-N 1,3-dibromobenzene Chemical compound BrC1=CC=CC(Br)=C1 JSRLURSZEMLAFO-UHFFFAOYSA-N 0.000 description 1
- AATPRMRVLQZEHB-UHFFFAOYSA-N 1,3-dichloro-5-iodobenzene Chemical compound ClC1=CC(Cl)=CC(I)=C1 AATPRMRVLQZEHB-UHFFFAOYSA-N 0.000 description 1
- SBHVNORGKIPGCL-UHFFFAOYSA-N 1,4-dichloro-2-iodobenzene Chemical compound ClC1=CC=C(Cl)C(I)=C1 SBHVNORGKIPGCL-UHFFFAOYSA-N 0.000 description 1
- WZINWJPRJHFUFF-UHFFFAOYSA-N 1-(2,5-dichlorophenyl)-3-(dimethylaminomethylidene)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC(Cl)=CC=C1Cl WZINWJPRJHFUFF-UHFFFAOYSA-N 0.000 description 1
- VFSGUNVIULIBNN-UHFFFAOYSA-N 1-(2-chlorophenyl)-3-(dimethylaminomethylidene)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC=C1Cl VFSGUNVIULIBNN-UHFFFAOYSA-N 0.000 description 1
- IFHPWXCMPNVMIW-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-3-(dimethylaminomethylidene)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=C(Cl)C(Cl)=C1 IFHPWXCMPNVMIW-UHFFFAOYSA-N 0.000 description 1
- PJERYLOUCRZXMY-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)-3-(dimethylaminomethylidene)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC(Cl)=CC(Cl)=C1 PJERYLOUCRZXMY-UHFFFAOYSA-N 0.000 description 1
- QASQITDVEOOESU-UHFFFAOYSA-N 1-(3-bromophenyl)-3-(dimethylaminomethylidene)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC(Br)=C1 QASQITDVEOOESU-UHFFFAOYSA-N 0.000 description 1
- VDXAFZUNXRJNLQ-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(1-ethylpyrrolidin-2-ylidene)indol-2-one Chemical compound CCN1CCCC1=C1C2=CC=CC=C2N(C=2C=C(Cl)C=CC=2)C1=O VDXAFZUNXRJNLQ-UHFFFAOYSA-N 0.000 description 1
- COUZZEPUNRDKLH-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(1-methylpiperidin-2-ylidene)indol-2-one Chemical compound CN1CCCCC1=C1C2=CC=CC=C2N(C=2C=C(Cl)C=CC=2)C1=O COUZZEPUNRDKLH-UHFFFAOYSA-N 0.000 description 1
- WVAJLWPUKFAQJF-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(1-methylpyrrolidin-2-ylidene)indol-2-one Chemical compound CN1CCCC1=C1C2=CC=CC=C2N(C=2C=C(Cl)C=CC=2)C1=O WVAJLWPUKFAQJF-UHFFFAOYSA-N 0.000 description 1
- NEPGBRUYIAFHCA-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(1-phenylpyrrolidin-2-ylidene)indol-2-one Chemical compound ClC1=CC=CC(N2C3=CC=CC=C3C(=C3N(CCC3)C=3C=CC=CC=3)C2=O)=C1 NEPGBRUYIAFHCA-UHFFFAOYSA-N 0.000 description 1
- MCBDPHFNCYYGFP-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(diethylaminomethylidene)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(CC)CC)C(=O)N1C1=CC=CC(Cl)=C1 MCBDPHFNCYYGFP-UHFFFAOYSA-N 0.000 description 1
- CBNOPNCYKCLUJV-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(ethoxymethylidene)indol-2-one Chemical compound C12=CC=CC=C2C(=COCC)C(=O)N1C1=CC=CC(Cl)=C1 CBNOPNCYKCLUJV-UHFFFAOYSA-N 0.000 description 1
- PEEIBFGKWVEZIN-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(piperidin-1-ylmethylidene)indol-2-one Chemical compound ClC1=CC=CC(N2C3=CC=CC=C3C(=CN3CCCCC3)C2=O)=C1 PEEIBFGKWVEZIN-UHFFFAOYSA-N 0.000 description 1
- VTVHMLCZDIQHQZ-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(pyrrolidin-1-ylmethylidene)indol-2-one Chemical compound ClC1=CC=CC(N2C3=CC=CC=C3C(=CN3CCCC3)C2=O)=C1 VTVHMLCZDIQHQZ-UHFFFAOYSA-N 0.000 description 1
- VZEPMNASMUXYAT-UHFFFAOYSA-N 1-(3-fluoro-4-methoxyphenyl)-3-(1-methylpyrrolidin-2-ylidene)indol-2-one Chemical compound C1=C(F)C(OC)=CC=C1N(C1=O)C2=CC=CC=C2C1=C1N(C)CCC1 VZEPMNASMUXYAT-UHFFFAOYSA-N 0.000 description 1
- WAJSBPBBXCQDNV-UHFFFAOYSA-N 1-(3-fluoro-4-methoxyphenyl)-3-pyrrolidin-2-ylideneindol-2-one Chemical compound C1=C(F)C(OC)=CC=C1N(C1=O)C2=CC=CC=C2C1=C1NCCC1 WAJSBPBBXCQDNV-UHFFFAOYSA-N 0.000 description 1
- AVVRKHDJLFCZQE-UHFFFAOYSA-N 1-(3-fluoro-4-methoxyphenyl)-3h-indol-2-one Chemical compound C1=C(F)C(OC)=CC=C1N1C2=CC=CC=C2CC1=O AVVRKHDJLFCZQE-UHFFFAOYSA-N 0.000 description 1
- BCIYGRKNVQHPJC-UHFFFAOYSA-N 1-(3-fluoro-4-methoxyphenyl)indole Chemical compound C1=C(F)C(OC)=CC=C1N1C2=CC=CC=C2C=C1 BCIYGRKNVQHPJC-UHFFFAOYSA-N 0.000 description 1
- MXCPHBSLBMIJIY-UHFFFAOYSA-N 1-(3-methoxyphenyl)-3-(1-methylpyrrolidin-2-ylidene)indol-2-one Chemical compound COC1=CC=CC(N2C3=CC=CC=C3C(=C3N(CCC3)C)C2=O)=C1 MXCPHBSLBMIJIY-UHFFFAOYSA-N 0.000 description 1
- CRMXFQJQMVOPOL-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-(1-methylpyrrolidin-2-ylidene)indol-2-one Chemical compound CN1CCCC1=C1C2=CC=CC=C2N(C=2C=CC(Cl)=CC=2)C1=O CRMXFQJQMVOPOL-UHFFFAOYSA-N 0.000 description 1
- NRHPFUANXBJPPX-UHFFFAOYSA-N 1-(4-methoxyphenyl)-3-(1-methylpyrrolidin-2-ylidene)indol-2-one Chemical compound C1=CC(OC)=CC=C1N(C1=O)C2=CC=CC=C2C1=C1N(C)CCC1 NRHPFUANXBJPPX-UHFFFAOYSA-N 0.000 description 1
- VHJPMNBCLKQSCV-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-(dimethylaminomethylidene)indol-2-one Chemical compound COC1=CC=C(Cl)C=C1N1C2=CC=CC=C2C(=CN(C)C)C1=O VHJPMNBCLKQSCV-UHFFFAOYSA-N 0.000 description 1
- UREZUFDECNTEKM-UHFFFAOYSA-N 1-(5-chloro-5-methoxycyclohexa-1,3-dien-1-yl)indole Chemical compound ClC1(CC(=CC=C1)N1C=CC2=CC=CC=C12)OC UREZUFDECNTEKM-UHFFFAOYSA-N 0.000 description 1
- ZFPGARUNNKGOBB-UHFFFAOYSA-N 1-Ethyl-2-pyrrolidinone Chemical compound CCN1CCCC1=O ZFPGARUNNKGOBB-UHFFFAOYSA-N 0.000 description 1
- AXRAXJKPCFKTIB-UHFFFAOYSA-N 1-[2-chloro-5-(trifluoromethyl)phenyl]-3-(dimethylaminomethylidene)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC(C(F)(F)F)=CC=C1Cl AXRAXJKPCFKTIB-UHFFFAOYSA-N 0.000 description 1
- NNMBNYHMJRJUBC-UHFFFAOYSA-N 1-bromo-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(Br)=C1 NNMBNYHMJRJUBC-UHFFFAOYSA-N 0.000 description 1
- JRGGUPZKKTVKOV-UHFFFAOYSA-N 1-bromo-3-chlorobenzene Chemical compound ClC1=CC=CC(Br)=C1 JRGGUPZKKTVKOV-UHFFFAOYSA-N 0.000 description 1
- PLDWAJLZAAHOGG-UHFFFAOYSA-N 1-bromo-3-methoxybenzene Chemical compound COC1=CC=CC(Br)=C1 PLDWAJLZAAHOGG-UHFFFAOYSA-N 0.000 description 1
- USYQKCQEVBFJRP-UHFFFAOYSA-N 1-bromo-3-phenylbenzene Chemical group BrC1=CC=CC(C=2C=CC=CC=2)=C1 USYQKCQEVBFJRP-UHFFFAOYSA-N 0.000 description 1
- AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 1
- ZBTMRBYMKUEVEU-UHFFFAOYSA-N 1-bromo-4-methylbenzene Chemical compound CC1=CC=C(Br)C=C1 ZBTMRBYMKUEVEU-UHFFFAOYSA-N 0.000 description 1
- YEUYZNNBXLMFCW-UHFFFAOYSA-N 1-bromo-4-methylsulfanylbenzene Chemical compound CSC1=CC=C(Br)C=C1 YEUYZNNBXLMFCW-UHFFFAOYSA-N 0.000 description 1
- MPEOPBCQHNWNFB-UHFFFAOYSA-N 1-chloro-2-iodobenzene Chemical compound ClC1=CC=CC=C1I MPEOPBCQHNWNFB-UHFFFAOYSA-N 0.000 description 1
- GWQSENYKCGJTRI-UHFFFAOYSA-N 1-chloro-4-iodobenzene Chemical compound ClC1=CC=C(I)C=C1 GWQSENYKCGJTRI-UHFFFAOYSA-N 0.000 description 1
- XSMZGZMBNXKCBW-UHFFFAOYSA-N 1-ethyl-3-iodobenzene Chemical compound CCC1=CC=CC(I)=C1 XSMZGZMBNXKCBW-UHFFFAOYSA-N 0.000 description 1
- JIXDOBAQOWOUPA-UHFFFAOYSA-N 1-fluoro-2-methoxybenzene Chemical compound COC1=CC=CC=C1F JIXDOBAQOWOUPA-UHFFFAOYSA-N 0.000 description 1
- RSHBAGGASAJQCH-UHFFFAOYSA-N 1-iodo-3-methoxybenzene Chemical compound COC1=CC=CC(I)=C1 RSHBAGGASAJQCH-UHFFFAOYSA-N 0.000 description 1
- VLCPISYURGTGLP-UHFFFAOYSA-N 1-iodo-3-methylbenzene Chemical compound CC1=CC=CC(I)=C1 VLCPISYURGTGLP-UHFFFAOYSA-N 0.000 description 1
- GGYVTHJIUNGKFZ-UHFFFAOYSA-N 1-methylpiperidin-2-one Chemical compound CN1CCCCC1=O GGYVTHJIUNGKFZ-UHFFFAOYSA-N 0.000 description 1
- JMVIVASFFKKFQK-UHFFFAOYSA-N 1-phenylpyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=CC=C1 JMVIVASFFKKFQK-UHFFFAOYSA-N 0.000 description 1
- IWVFFVBJTCPIIG-UHFFFAOYSA-N 2,2-dimethoxy-1-methylpyrrolidine Chemical compound COC1(OC)CCCN1C IWVFFVBJTCPIIG-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- YJEMGEBDXDPBSP-UHFFFAOYSA-N 2-bromo-4-chloro-1-methoxybenzene Chemical compound COC1=CC=C(Cl)C=C1Br YJEMGEBDXDPBSP-UHFFFAOYSA-N 0.000 description 1
- VXXHSCYVTXDCOQ-UHFFFAOYSA-N 2-chloro-n-(3-fluorophenyl)-n-phenylacetamide Chemical compound FC1=CC=CC(N(C(=O)CCl)C=2C=CC=CC=2)=C1 VXXHSCYVTXDCOQ-UHFFFAOYSA-N 0.000 description 1
- VONWPEXRCLHKRJ-UHFFFAOYSA-N 2-chloro-n-phenylacetamide Chemical compound ClCC(=O)NC1=CC=CC=C1 VONWPEXRCLHKRJ-UHFFFAOYSA-N 0.000 description 1
- KVTHPKXDLVYNCH-UHFFFAOYSA-N 2-iodoethylbenzene Chemical compound ICCC1=CC=CC=C1 KVTHPKXDLVYNCH-UHFFFAOYSA-N 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- BYYBRYZOYYZEHM-UHFFFAOYSA-N 3-(1-aminoethylidene)-1-(3-chlorophenyl)indol-2-one Chemical compound C12=CC=CC=C2C(=C(N)C)C(=O)N1C1=CC=CC(Cl)=C1 BYYBRYZOYYZEHM-UHFFFAOYSA-N 0.000 description 1
- LDIDVQLJJZGPFA-UHFFFAOYSA-N 3-(azepan-2-ylidene)-1-phenylindol-2-one Chemical compound O=C1N(C=2C=CC=CC=2)C2=CC=CC=C2C1=C1CCCCCN1 LDIDVQLJJZGPFA-UHFFFAOYSA-N 0.000 description 1
- ZWYJJXVNZAZDBX-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(2-methylphenyl)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC=C1C ZWYJJXVNZAZDBX-UHFFFAOYSA-N 0.000 description 1
- QPRBIHINGXPMSV-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(2-nitrophenyl)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC=C1[N+]([O-])=O QPRBIHINGXPMSV-UHFFFAOYSA-N 0.000 description 1
- FBCMGBHNJZWXPJ-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(3-ethoxyphenyl)indol-2-one Chemical compound CCOC1=CC=CC(N2C3=CC=CC=C3C(=CN(C)C)C2=O)=C1 FBCMGBHNJZWXPJ-UHFFFAOYSA-N 0.000 description 1
- NAECXAKUBOEYKG-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(3-ethylphenyl)indol-2-one Chemical compound CCC1=CC=CC(N2C3=CC=CC=C3C(=CN(C)C)C2=O)=C1 NAECXAKUBOEYKG-UHFFFAOYSA-N 0.000 description 1
- IAHSKFKKMVUMQI-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(3-fluorophenyl)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC(F)=C1 IAHSKFKKMVUMQI-UHFFFAOYSA-N 0.000 description 1
- ALBZTMSIWNDQNZ-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(3-methylphenyl)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC(C)=C1 ALBZTMSIWNDQNZ-UHFFFAOYSA-N 0.000 description 1
- REWBLTPKDSHHCU-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(3-nitrophenyl)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC([N+]([O-])=O)=C1 REWBLTPKDSHHCU-UHFFFAOYSA-N 0.000 description 1
- RQSWTIKRQNQDNE-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(4-methoxy-3-methylphenyl)indol-2-one Chemical compound C1=C(C)C(OC)=CC=C1N1C2=CC=CC=C2C(=CN(C)C)C1=O RQSWTIKRQNQDNE-UHFFFAOYSA-N 0.000 description 1
- UQCLISBGORGAMN-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(4-methoxy-3-propan-2-ylphenyl)indol-2-one Chemical compound C1=C(C(C)C)C(OC)=CC=C1N1C2=CC=CC=C2C(=CN(C)C)C1=O UQCLISBGORGAMN-UHFFFAOYSA-N 0.000 description 1
- AMROQQUQERDSBQ-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(4-methoxyphenyl)indol-2-one Chemical compound C1=CC(OC)=CC=C1N1C2=CC=CC=C2C(=CN(C)C)C1=O AMROQQUQERDSBQ-UHFFFAOYSA-N 0.000 description 1
- XOQIZPDLTUEEHP-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(4-methylphenyl)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=C(C)C=C1 XOQIZPDLTUEEHP-UHFFFAOYSA-N 0.000 description 1
- XDYKHROCUOBYOK-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(4-methylsulfanylphenyl)indol-2-one Chemical compound C1=CC(SC)=CC=C1N1C2=CC=CC=C2C(=CN(C)C)C1=O XDYKHROCUOBYOK-UHFFFAOYSA-N 0.000 description 1
- YQRWFZAXNUIXMA-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-(4-nitrophenyl)indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=C([N+]([O-])=O)C=C1 YQRWFZAXNUIXMA-UHFFFAOYSA-N 0.000 description 1
- ATBBJFHLPIXWEF-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-[3-(trifluoromethyl)phenyl]indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 ATBBJFHLPIXWEF-UHFFFAOYSA-N 0.000 description 1
- ZGILCWZYOQKQJZ-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-1-[4-(dimethylamino)phenyl]indol-2-one Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=C(N(C)C)C=C1 ZGILCWZYOQKQJZ-UHFFFAOYSA-N 0.000 description 1
- UDCOEZKGMFWULH-UHFFFAOYSA-N 3-(dimethylaminomethylidene)-5-methoxy-1h-indol-2-one Chemical compound COC1=CC=C2NC(=O)C(=CN(C)C)C2=C1 UDCOEZKGMFWULH-UHFFFAOYSA-N 0.000 description 1
- UJEQSVRYCYXBIJ-UHFFFAOYSA-N 3-[(benzylamino)methylidene]-1-(3-chlorophenyl)indol-2-one Chemical compound ClC1=CC=CC(N2C3=CC=CC=C3C(=CNCC=3C=CC=CC=3)C2=O)=C1 UJEQSVRYCYXBIJ-UHFFFAOYSA-N 0.000 description 1
- YFCJDYAKFXYRSK-UHFFFAOYSA-N 3-[1-(dimethylamino)ethylidene]-1-(3-methylphenyl)indol-2-one Chemical compound C12=CC=CC=C2C(=C(C)N(C)C)C(=O)N1C1=CC=CC(C)=C1 YFCJDYAKFXYRSK-UHFFFAOYSA-N 0.000 description 1
- KFRVPIVORKPRNZ-UHFFFAOYSA-N 3-[1-(dimethylamino)ethylidene]-1h-indol-2-one Chemical compound C1=CC=C2C(=C(C)N(C)C)C(=O)NC2=C1 KFRVPIVORKPRNZ-UHFFFAOYSA-N 0.000 description 1
- KVZSZBIGZHEXIH-UHFFFAOYSA-N 3-[1-[(4-chlorophenyl)methyl]pyrrolidin-2-ylidene]-1h-indol-2-one Chemical compound C1=CC(Cl)=CC=C1CN(CCC1)C1=C1C2=CC=CC=C2NC1=O KVZSZBIGZHEXIH-UHFFFAOYSA-N 0.000 description 1
- PERGPWLPUDHGRA-UHFFFAOYSA-N 3-[3-(dimethylaminomethylidene)-2-oxoindol-1-yl]-n,n-dimethylbenzamide Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC(C(=O)N(C)C)=C1 PERGPWLPUDHGRA-UHFFFAOYSA-N 0.000 description 1
- QKWMAWKCCFEYBR-UHFFFAOYSA-N 3-[3-(dimethylaminomethylidene)-2-oxoindol-1-yl]benzaldehyde Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC(C=O)=C1 QKWMAWKCCFEYBR-UHFFFAOYSA-N 0.000 description 1
- AEVKVYMKBXAAQU-UHFFFAOYSA-N 3-[3-(dimethylaminomethylidene)-2-oxoindol-1-yl]benzonitrile Chemical compound C12=CC=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC(C#N)=C1 AEVKVYMKBXAAQU-UHFFFAOYSA-N 0.000 description 1
- AMKPQMFZCBTTAT-UHFFFAOYSA-N 3-ethylaniline Chemical compound CCC1=CC=CC(N)=C1 AMKPQMFZCBTTAT-UHFFFAOYSA-N 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- TVFNKBQQVHGWAF-UHFFFAOYSA-N 3-iodo-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC(I)=C1 TVFNKBQQVHGWAF-UHFFFAOYSA-N 0.000 description 1
- XSLDOPYONMGECY-UHFFFAOYSA-N 3-iodo-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC(I)=C1 XSLDOPYONMGECY-UHFFFAOYSA-N 0.000 description 1
- RZODAQZAFOBFLS-UHFFFAOYSA-N 3-iodobenzaldehyde Chemical compound IC1=CC=CC(C=O)=C1 RZODAQZAFOBFLS-UHFFFAOYSA-N 0.000 description 1
- KBTMGSMZIKLAHN-UHFFFAOYSA-N 4-bromo-1,2-dimethoxybenzene Chemical compound COC1=CC=C(Br)C=C1OC KBTMGSMZIKLAHN-UHFFFAOYSA-N 0.000 description 1
- UDLRGQOHGYWLCS-UHFFFAOYSA-N 4-bromo-1-methoxy-2-methylbenzene Chemical compound COC1=CC=C(Br)C=C1C UDLRGQOHGYWLCS-UHFFFAOYSA-N 0.000 description 1
- XYZWMVYYUIMRIZ-UHFFFAOYSA-N 4-bromo-n,n-dimethylaniline Chemical compound CN(C)C1=CC=C(Br)C=C1 XYZWMVYYUIMRIZ-UHFFFAOYSA-N 0.000 description 1
- XNSPDJAXCBZCRV-UHFFFAOYSA-N 4-chloro-1,3-dihydroindol-2-one Chemical compound ClC1=CC=CC2=C1CC(=O)N2 XNSPDJAXCBZCRV-UHFFFAOYSA-N 0.000 description 1
- PWWNYLHSUWWGMS-UHFFFAOYSA-N 4-chloro-1-phenyl-3h-indol-2-one Chemical compound O=C1CC=2C(Cl)=CC=CC=2N1C1=CC=CC=C1 PWWNYLHSUWWGMS-UHFFFAOYSA-N 0.000 description 1
- FIMIBEZIDLGDTP-UHFFFAOYSA-N 4-chloro-3-(1-methylpyrrolidin-2-ylidene)-1-phenylindol-2-one Chemical compound CN1CCCC1=C1C2=C(Cl)C=CC=C2N(C=2C=CC=CC=2)C1=O FIMIBEZIDLGDTP-UHFFFAOYSA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- VCOONNWIINSFBA-UHFFFAOYSA-N 4-methoxy-n-(4-methoxyphenyl)aniline Chemical compound C1=CC(OC)=CC=C1NC1=CC=C(OC)C=C1 VCOONNWIINSFBA-UHFFFAOYSA-N 0.000 description 1
- YSTRJVIMBHPGBW-UHFFFAOYSA-N 5-bromo-1-chloro-2-methoxy-3-methylbenzene Chemical compound COC1=C(C)C=C(Br)C=C1Cl YSTRJVIMBHPGBW-UHFFFAOYSA-N 0.000 description 1
- UTFMREHHJDJDHV-UHFFFAOYSA-N 5-bromo-1-chloro-2-methoxy-3-methylbenzene 4-bromo-2-chloro-6-methylphenol Chemical compound BrC1=CC(=C(C(=C1)C)O)Cl.BrC1=CC(=C(C(=C1)C)OC)Cl UTFMREHHJDJDHV-UHFFFAOYSA-N 0.000 description 1
- WWJLCYHYLZZXBE-UHFFFAOYSA-N 5-chloro-1,3-dihydroindol-2-one Chemical compound ClC1=CC=C2NC(=O)CC2=C1 WWJLCYHYLZZXBE-UHFFFAOYSA-N 0.000 description 1
- WFHPYIHAYNFKBL-UHFFFAOYSA-N 5-chloro-1-(3-chlorophenyl)-3-(dimethylaminomethylidene)indol-2-one Chemical compound C12=CC=C(Cl)C=C2C(=CN(C)C)C(=O)N1C1=CC=CC(Cl)=C1 WFHPYIHAYNFKBL-UHFFFAOYSA-N 0.000 description 1
- JROITAAGUGWVPQ-UHFFFAOYSA-N 5-chloro-3-(dimethylaminomethylidene)-1h-indol-2-one Chemical compound C1=C(Cl)C=C2C(=CN(C)C)C(=O)NC2=C1 JROITAAGUGWVPQ-UHFFFAOYSA-N 0.000 description 1
- XRQRDFDSCDYWHL-UHFFFAOYSA-N 5-fluoro-1-(4-fluorophenyl)indole-2,3-dione Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(F)C=C2C(=O)C1=O XRQRDFDSCDYWHL-UHFFFAOYSA-N 0.000 description 1
- DFGZEOUBIHLXFD-UHFFFAOYSA-N 5-methoxy-1,3-dihydroindol-2-one Chemical compound COC1=CC=C2NC(=O)CC2=C1 DFGZEOUBIHLXFD-UHFFFAOYSA-N 0.000 description 1
- ILQQTNGQOOKNAZ-UHFFFAOYSA-N 6-chloro-1-(3-chlorophenyl)-3-(1-methylpyrrolidin-2-ylidene)indol-2-one Chemical compound CN1CCCC1=C1C2=CC=C(Cl)C=C2N(C=2C=C(Cl)C=CC=2)C1=O ILQQTNGQOOKNAZ-UHFFFAOYSA-N 0.000 description 1
- DDYWMHMTGCZYCT-UHFFFAOYSA-N 6-chloro-1-(3-chlorophenyl)-3-(dimethylaminomethylidene)indol-2-one Chemical compound C12=CC(Cl)=CC=C2C(=CN(C)C)C(=O)N1C1=CC=CC(Cl)=C1 DDYWMHMTGCZYCT-UHFFFAOYSA-N 0.000 description 1
- RODFNSPAVUHIRI-UHFFFAOYSA-N 6-chloro-1-phenyl-3-(2-pyrrolidin-1-ylethylidene)indol-2-one Chemical compound O=C1N(C=2C=CC=CC=2)C2=CC(Cl)=CC=C2C1=CCN1CCCC1 RODFNSPAVUHIRI-UHFFFAOYSA-N 0.000 description 1
- PZHOLNGYBPIXBF-UHFFFAOYSA-N 6-chloro-3-(1-methylpyrrolidin-2-ylidene)-1-phenylindol-2-one Chemical compound CN1CCCC1=C1C2=CC=C(Cl)C=C2N(C=2C=CC=CC=2)C1=O PZHOLNGYBPIXBF-UHFFFAOYSA-N 0.000 description 1
- RRSNVPDKKSDGLH-UHFFFAOYSA-N 6-chloro-3-(1-methylpyrrolidin-2-ylidene)-1h-indol-2-one Chemical compound CN1CCCC1=C1C2=CC=C(Cl)C=C2NC1=O RRSNVPDKKSDGLH-UHFFFAOYSA-N 0.000 description 1
- YJDOALCKVFVBTA-UHFFFAOYSA-N 6-chloro-3-(dimethylaminomethylidene)-1h-indol-2-one Chemical compound ClC1=CC=C2C(=CN(C)C)C(=O)NC2=C1 YJDOALCKVFVBTA-UHFFFAOYSA-N 0.000 description 1
- NOAZGMVHHABVFQ-UHFFFAOYSA-N 6-chloro-3-[1-(dimethylamino)ethylidene]-1-phenylindol-2-one Chemical compound C12=CC(Cl)=CC=C2C(=C(C)N(C)C)C(=O)N1C1=CC=CC=C1 NOAZGMVHHABVFQ-UHFFFAOYSA-N 0.000 description 1
- FPDLUAACCNVSQA-UHFFFAOYSA-N 7-chloro-1,3-dihydroindol-2-one Chemical compound ClC1=CC=CC2=C1NC(=O)C2 FPDLUAACCNVSQA-UHFFFAOYSA-N 0.000 description 1
- MHQOUBPMFXUNBS-UHFFFAOYSA-N 7-chloro-1-(3-chlorophenyl)-3-(dimethylaminomethylidene)indol-2-one Chemical compound C1=CC=C(Cl)C2=C1C(=CN(C)C)C(=O)N2C1=CC=CC(Cl)=C1 MHQOUBPMFXUNBS-UHFFFAOYSA-N 0.000 description 1
- USWWIUOAUXGJSF-UHFFFAOYSA-N 7-chloro-3-(dimethylaminomethylidene)-1h-indol-2-one Chemical compound C1=CC=C(Cl)C2=C1C(=CN(C)C)C(=O)N2 USWWIUOAUXGJSF-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- NIIBCILGPYPNCT-UHFFFAOYSA-N C(C1=CC=CC=C1)N1C(CCC1)=O.ClC=1C=C(C=CC1)N1C(C(C2=CC=CC=C12)=C1N(CCC1)CC1=CC=CC=C1)=O Chemical compound C(C1=CC=CC=C1)N1C(CCC1)=O.ClC=1C=C(C=CC1)N1C(C(C2=CC=CC=C12)=C1N(CCC1)CC1=CC=CC=C1)=O NIIBCILGPYPNCT-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical group OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- KLPWJLBORRMFGK-UHFFFAOYSA-N Molindone Chemical compound O=C1C=2C(CC)=C(C)NC=2CCC1CN1CCOCC1 KLPWJLBORRMFGK-UHFFFAOYSA-N 0.000 description 1
- 229910004013 NO 2 Inorganic materials 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 150000008061 acetanilides Chemical class 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 150000003931 anilides Chemical class 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
- GFCIRCPKSSUESK-UHFFFAOYSA-N chembl336667 Chemical compound OC1=C(C=N)C2=CC=CC=C2N1C1=CC=CC(Cl)=C1 GFCIRCPKSSUESK-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 208000027744 congestion Diseases 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 230000020335 dealkylation Effects 0.000 description 1
- 238000006900 dealkylation reaction Methods 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- DLLJVQNYBYOKGS-UHFFFAOYSA-N ethoxyethane;pentane Chemical compound CCCCC.CCOCC DLLJVQNYBYOKGS-UHFFFAOYSA-N 0.000 description 1
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960002200 flunitrazepam Drugs 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 229960004938 molindone Drugs 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- FJBXUPTZWOHNJT-UHFFFAOYSA-N n,n-dimethyl-3-[3-(1-methylpyrrolidin-2-ylidene)-2-oxoindol-1-yl]benzamide Chemical compound CN(C)C(=O)C1=CC=CC(N2C3=CC=CC=C3C(=C3N(CCC3)C)C2=O)=C1 FJBXUPTZWOHNJT-UHFFFAOYSA-N 0.000 description 1
- JHEFOJNPLXSWNZ-UHFFFAOYSA-N n-(4-fluorophenyl)acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1 JHEFOJNPLXSWNZ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- XREXPQGDOPQPAH-QKUPJAQQSA-K trisodium;[(z)-18-[1,3-bis[[(z)-12-sulfonatooxyoctadec-9-enoyl]oxy]propan-2-yloxy]-18-oxooctadec-9-en-7-yl] sulfate Chemical compound [Na+].[Na+].[Na+].CCCCCCC(OS([O-])(=O)=O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(CCCCCC)OS([O-])(=O)=O)COC(=O)CCCCCCC\C=C/CC(CCCCCC)OS([O-])(=O)=O XREXPQGDOPQPAH-QKUPJAQQSA-K 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/38—Oxygen atoms in positions 2 and 3, e.g. isatin
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Psychiatry (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Dental Preparations (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/420,544 US4476307A (en) | 1982-09-20 | 1982-09-20 | Heteroylidene indolone compounds |
| US42054482 | 1982-09-20 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI833335A0 FI833335A0 (fi) | 1983-09-19 |
| FI833335A7 FI833335A7 (fi) | 1984-03-21 |
| FI77446B FI77446B (fi) | 1988-11-30 |
| FI77446C true FI77446C (fi) | 1989-03-10 |
Family
ID=23666904
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI833335A FI77446C (fi) | 1982-09-20 | 1983-09-19 | Foerfarande foer framstaellning av psykoterapeutiskt anvaendbara 1-fenyl-2(1h,3h)-indoloner. |
Country Status (24)
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4879391A (en) * | 1982-09-20 | 1989-11-07 | Pfizer Inc. | 1-Phenyl-2(1H,3H)-indolone psychotherapeutic agents |
| US4760083A (en) * | 1986-04-10 | 1988-07-26 | E. I. Dupont De Nemours & Company | 3,3-disubstituted indolines |
| WO1990008146A1 (en) * | 1989-01-10 | 1990-07-26 | Pfizer Inc. | Anti-inflammatory 1-heteroaryl-oxindole-3-carboxamides |
| US5078756A (en) * | 1990-01-12 | 1992-01-07 | Major Thomas O | Apparatus and method for purification and recovery of refrigerant |
| US5158969A (en) * | 1991-08-21 | 1992-10-27 | Neurosearch A/S | Indole derivatives as potassium channel blockers |
| US5760250A (en) * | 1991-11-05 | 1998-06-02 | Zeneca Limited | Process for the preparation of 3-(α-methoxy)methylenebenzofuranones and intermediates therefor |
| DE19949209A1 (de) * | 1999-10-13 | 2001-04-19 | Boehringer Ingelheim Pharma | In 5-Stellung substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| WO2003027102A1 (en) * | 2001-09-27 | 2003-04-03 | Allergan, Inc. | 3-(arylamino)methylene-1, 3-dihydro-2h-indol-2-ones as kinase inhibitors |
| IL163992A0 (en) * | 2002-03-27 | 2005-12-18 | Lundbeck & Co As H | Method for manufacture of sertindole |
| FR2847811B1 (fr) * | 2002-11-29 | 2005-01-07 | Oreal | Composition filtrante contenant au moins un derive du dibenzoylmethane et au moins un derive de 3-(2-azacycloalkylidene)-1,3-dihydro-indol-2-one;procede de photostabilisation |
| FR2847813A1 (fr) * | 2002-11-29 | 2004-06-04 | Oreal | Compositions cosmetiques photoprotectrices contenant des derives de 3-(2-azacycloalkylidene)-1,3-dihydro-indol-2-one et utilisations |
| SI1928454T1 (sl) | 2005-05-10 | 2015-01-30 | Intermune, Inc. | Piridonski derivati za moduliranje s stresom aktiviranega protein kinaznega sistema |
| US8304413B2 (en) | 2008-06-03 | 2012-11-06 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| CN104761533B (zh) | 2008-12-19 | 2017-12-05 | 日本曹达株式会社 | 1‑杂原子二烯衍生物及有害生物防除剂 |
| NZ599682A (en) | 2009-11-12 | 2013-06-28 | Nippon Soda Co | 1-heterodiene derivative and noxious organism control agent |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| CA2891122C (en) | 2012-11-14 | 2021-07-20 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| KR102373700B1 (ko) | 2014-04-02 | 2022-03-11 | 인터뮨, 인크. | 항섬유성 피리디논 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3506683A (en) * | 1963-10-07 | 1970-04-14 | Upjohn Co | 3-(2-pyrrolidinylidene)-3h-indoles |
| GB1237008A (en) * | 1968-12-18 | 1971-06-30 | Pfizer Ltd | Novel indoline derivatives |
| US3723457A (en) * | 1969-09-30 | 1973-03-27 | Eisai Co Ltd | Indoline-2-one derivatives and preparation thereof |
| GB1374414A (en) * | 1972-06-12 | 1974-11-20 | Sterling Drug Inc | 1-acyl-3-amino-alkyl-indoles and their preparation |
| DE2557342A1 (de) * | 1975-12-19 | 1977-06-30 | Hoechst Ag | Basisch substituierte indolderivate und verfahren zu ihrer herstellung |
-
1982
- 1982-09-20 US US06/420,544 patent/US4476307A/en not_active Expired - Fee Related
-
1983
- 1983-09-16 CA CA000436845A patent/CA1194871A/en not_active Expired
- 1983-09-18 IL IL69758A patent/IL69758A/xx unknown
- 1983-09-19 DK DK425383A patent/DK157010C/da not_active IP Right Cessation
- 1983-09-19 AT AT83305484T patent/ATE25972T1/de not_active IP Right Cessation
- 1983-09-19 ZA ZA836933A patent/ZA836933B/xx unknown
- 1983-09-19 NZ NZ205638A patent/NZ205638A/en unknown
- 1983-09-19 DD DD83254923A patent/DD213211A5/de unknown
- 1983-09-19 IE IE2193/83A patent/IE55923B1/en not_active IP Right Cessation
- 1983-09-19 AU AU19252/83A patent/AU543115B2/en not_active Ceased
- 1983-09-19 HU HU833235A patent/HU189747B/hu unknown
- 1983-09-19 ES ES525737A patent/ES8503328A1/es not_active Expired
- 1983-09-19 NO NO833367A patent/NO161557C/no unknown
- 1983-09-19 DE DE8383305484T patent/DE3370325D1/de not_active Expired
- 1983-09-19 FI FI833335A patent/FI77446C/fi not_active IP Right Cessation
- 1983-09-19 KR KR1019830004396A patent/KR860001270B1/ko not_active Expired
- 1983-09-19 SU SU833646758A patent/SU1272983A3/ru active
- 1983-09-19 EP EP83305484A patent/EP0104860B1/en not_active Expired
- 1983-09-19 PT PT77360A patent/PT77360B/pt not_active IP Right Cessation
- 1983-09-19 GR GR72470A patent/GR79732B/el unknown
- 1983-09-20 YU YU01892/83A patent/YU189283A/xx unknown
- 1983-09-20 PL PL1983250769A patent/PL141876B1/pl unknown
- 1983-09-20 PL PL1983243826A patent/PL141609B1/pl unknown
- 1983-09-20 JP JP58174025A patent/JPS5976058A/ja active Granted
- 1983-09-20 PL PL1983250768A patent/PL141370B1/pl unknown
- 1983-09-20 PH PH29565A patent/PH18297A/en unknown
-
1984
- 1984-04-25 ES ES531908A patent/ES531908A0/es active Granted
- 1984-04-25 ES ES531907A patent/ES531907A0/es active Granted
-
1986
- 1986-10-01 YU YU01693/86A patent/YU169386A/xx unknown
- 1986-10-01 YU YU01691/86A patent/YU169186A/xx unknown
- 1986-10-01 YU YU01692/86A patent/YU169286A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI77446C (fi) | Foerfarande foer framstaellning av psykoterapeutiskt anvaendbara 1-fenyl-2(1h,3h)-indoloner. | |
| US6166040A (en) | Indole compounds | |
| HU193941B (en) | Process for production of 6-substituted-4-dialkil-tetra-hydrobenz/c,d/ indole derivatives | |
| SE465928B (sv) | 1,2,4-triazolonfoereningar med antidepressiv aktivitet, foerfarande foer framstaellning av dessa och en farmaceutisk komposition | |
| US6114530A (en) | Isoquinolinamine and phthalazinamine derivatives: corticotropin-releasing factor receptor CRF1 specific ligands | |
| Ogawa et al. | Orally active, nonpeptide vasopressin V1 antagonists. A novel series of 1-(1-substituted 4-piperidyl)-3, 4-dihydro-2 (1H)-quinolinones | |
| US4607039A (en) | Quinoline derivatives which are 5-hydroxytryptamine antagonists | |
| Clark et al. | Some observations on the formation of 1‐hydroxyindoles in the leimgruber‐batcho indole synthesis | |
| JPS60158170A (ja) | エテニルフェノールインドール誘導体及びそれらの塩、これらの製造方法並びにこれらを含有する薬剤 | |
| US5773448A (en) | Pharmaceutical compounds | |
| FI61879B (fi) | Analogifoerfarande foer framstaellning av nya terapeutiskt effektiva aminopyrrolderivat | |
| US4879391A (en) | 1-Phenyl-2(1H,3H)-indolone psychotherapeutic agents | |
| US4861880A (en) | 1-phenyl-2(1H,3H)-indolone psycho-therapeutic agents | |
| US4977178A (en) | Method of treating anxiety and depression with 1-phenyl-2(1H,3H)-indolone psycho-therapeutic agents | |
| CA1334756C (en) | 6-fluoro-1,4-dihydroquinol-4-one-3-carboxylic acid derivatives and intermediates therefor | |
| CA2056065C (en) | Preparation of 3-alkylated indoles | |
| SU1473710A3 (ru) | Способ получени тиокетеновых производных пиперидина или их кислотно-аддитивных солей | |
| KR860001272B1 (ko) | 1-페닐-2(1h, 3h)-인돌온 유도체의 제조방법 | |
| US3712903A (en) | 5(1-(phenyl or benzyl)-1h-indazol-3-yloxymethyl)-tetrazoles | |
| KR860001297B1 (ko) | 1-페닐-2(1h, 3h)-인돌온 유도체의 제조방법 | |
| US5512566A (en) | Tricyclic compounds having affinity for the 5-HT1A receptor | |
| KR860001271B1 (ko) | 1-페닐 -2(1h, 3h)-인돌온유도체의 제조방법 | |
| CA1187079A (en) | 2,3,4,5-tetrahydro-1h-pyrido[4,3-b] indole derivatives and their preparation | |
| AU652740B2 (en) | New aryl- and heteroarylethenylene derivatives and process for their preparation | |
| Aanandhi et al. | Synthesis, anticonvulsant and antimicrobial activities of novel mannich bases of isatin derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: PFIZER INC. |