CH622248A5 - - Google Patents
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- Publication number
- CH622248A5 CH622248A5 CH1473575A CH1473575A CH622248A5 CH 622248 A5 CH622248 A5 CH 622248A5 CH 1473575 A CH1473575 A CH 1473575A CH 1473575 A CH1473575 A CH 1473575A CH 622248 A5 CH622248 A5 CH 622248A5
- Authority
- CH
- Switzerland
- Prior art keywords
- indole
- hydroxy
- methyl
- propoxy
- group
- Prior art date
Links
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- -1 pivaloyloxyalkyl Chemical group 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000005358 mercaptoalkyl group Chemical group 0.000 claims description 3
- MXZROAOUCUVNHX-UHFFFAOYSA-N 2-Aminopropanol Chemical class CCC(N)O MXZROAOUCUVNHX-UHFFFAOYSA-N 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 238000007127 saponification reaction Methods 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 2
- 125000003277 amino group Chemical group 0.000 claims 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 120
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 104
- 239000000243 solution Substances 0.000 description 56
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 55
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 49
- 239000000203 mixture Substances 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 235000019439 ethyl acetate Nutrition 0.000 description 36
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 29
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 26
- 239000002244 precipitate Substances 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 229960000583 acetic acid Drugs 0.000 description 18
- 239000005711 Benzoic acid Substances 0.000 description 16
- 235000010233 benzoic acid Nutrition 0.000 description 16
- 239000012071 phase Substances 0.000 description 16
- 239000007858 starting material Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 12
- 238000001035 drying Methods 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000009835 boiling Methods 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- OOYYYGHTDAWUEM-UHFFFAOYSA-N ethyl 6-methyl-4-(oxiran-2-ylmethoxy)-1h-indole-2-carboxylate Chemical compound C1=C(C)C=C2NC(C(=O)OCC)=CC2=C1OCC1CO1 OOYYYGHTDAWUEM-UHFFFAOYSA-N 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- IAPHVIZWSLCDAP-UHFFFAOYSA-N 2,6-dimethyl-4-(oxiran-2-ylmethoxy)-1h-indole Chemical compound C1=C(C)C=C2NC(C)=CC2=C1OCC1CO1 IAPHVIZWSLCDAP-UHFFFAOYSA-N 0.000 description 5
- BKAHBWRBBQERJX-UHFFFAOYSA-N 6-methyl-4-(oxiran-2-ylmethoxy)-1h-indole Chemical compound C=12C=CNC2=CC(C)=CC=1OCC1CO1 BKAHBWRBBQERJX-UHFFFAOYSA-N 0.000 description 5
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 5
- KLXCCAHKAQVZID-UHFFFAOYSA-N [4-(oxiran-2-ylmethoxy)-1h-indol-6-yl]methanol Chemical compound C=12C=CNC2=CC(CO)=CC=1OCC1CO1 KLXCCAHKAQVZID-UHFFFAOYSA-N 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 239000008240 homogeneous mixture Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- RPNOVLRYIWAXHI-UHFFFAOYSA-N ethyl 6-methyl-4-phenylmethoxy-1h-indole-2-carboxylate Chemical compound C1=C(C)C=C2NC(C(=O)OCC)=CC2=C1OCC1=CC=CC=C1 RPNOVLRYIWAXHI-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 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
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- VXAFVBJJVIRUQI-UHFFFAOYSA-N (4-phenylmethoxy-1h-indol-6-yl)methyl acetate Chemical compound C=12C=CNC2=CC(COC(=O)C)=CC=1OCC1=CC=CC=C1 VXAFVBJJVIRUQI-UHFFFAOYSA-N 0.000 description 3
- UOECUVCEIKBPOI-UHFFFAOYSA-N (6-methyl-4-phenylmethoxy-1H-indol-2-yl)methyl acetate Chemical compound C(C1=CC=CC=C1)OC1=C2C=C(NC2=CC(=C1)C)COC(C)=O UOECUVCEIKBPOI-UHFFFAOYSA-N 0.000 description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 3
- FYINBJOEKNGBDG-UHFFFAOYSA-N 6-methyl-4-(oxiran-2-ylmethoxy)-1h-indole-2-carboxamide Chemical compound C=12C=C(C(N)=O)NC2=CC(C)=CC=1OCC1CO1 FYINBJOEKNGBDG-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- VCDNGAOUMLSXDW-UHFFFAOYSA-N [4-(oxiran-2-ylmethoxy)-1h-indol-2-yl]methyl 2,2-dimethylpropanoate Chemical compound C1=CC=C2NC(COC(=O)C(C)(C)C)=CC2=C1OCC1CO1 VCDNGAOUMLSXDW-UHFFFAOYSA-N 0.000 description 3
- 238000004061 bleaching Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- XJCFYLIFUDJSKO-UHFFFAOYSA-N ethyl 4-[2-hydroxy-3-(propan-2-ylamino)propoxy]-6-methyl-1h-indole-2-carboxylate Chemical compound C1=C(C)C=C2NC(C(=O)OCC)=CC2=C1OCC(O)CNC(C)C XJCFYLIFUDJSKO-UHFFFAOYSA-N 0.000 description 3
- MPUAZMJTTWCGKH-UHFFFAOYSA-N ethyl 4-[3-(tert-butylamino)-2-hydroxypropoxy]-6-methyl-1h-indole-2-carboxylate Chemical compound C1=C(C)C=C2NC(C(=O)OCC)=CC2=C1OCC(O)CNC(C)(C)C MPUAZMJTTWCGKH-UHFFFAOYSA-N 0.000 description 3
- 230000007717 exclusion Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- METVUTLEWWTUHV-UHFFFAOYSA-N (6-methyl-4-phenylmethoxy-1h-indol-2-yl)methanol Chemical compound C=12C=C(CO)NC2=CC(C)=CC=1OCC1=CC=CC=C1 METVUTLEWWTUHV-UHFFFAOYSA-N 0.000 description 2
- QKJINCZWHIEPCR-UHFFFAOYSA-N 1-(tert-butylamino)-3-[(6-methyl-1h-indol-4-yl)oxy]propan-2-ol Chemical compound CC1=CC(OCC(O)CNC(C)(C)C)=C2C=CNC2=C1 QKJINCZWHIEPCR-UHFFFAOYSA-N 0.000 description 2
- SBRZSQZIODPBEN-UHFFFAOYSA-N 1-(tert-butylamino)-3-[[2-(hydroxymethyl)-6-methyl-1H-indol-4-yl]oxy]propan-2-ol Chemical compound OC(COC1=C2C=C(NC2=CC(=C1)C)CO)CNC(C)(C)C SBRZSQZIODPBEN-UHFFFAOYSA-N 0.000 description 2
- MEFNKHNKCQSKLT-UHFFFAOYSA-N 1-(tert-butylamino)-3-[[6-(hydroxymethyl)-1h-indol-4-yl]oxy]propan-2-ol Chemical compound CC(C)(C)NCC(O)COC1=CC(CO)=CC2=C1C=CN2 MEFNKHNKCQSKLT-UHFFFAOYSA-N 0.000 description 2
- HFZGABWMSVUTEX-UHFFFAOYSA-N 1-[(6-methyl-1h-indol-4-yl)oxy]-3-(propan-2-ylamino)propan-2-ol Chemical compound CC(C)NCC(O)COC1=CC(C)=CC2=C1C=CN2 HFZGABWMSVUTEX-UHFFFAOYSA-N 0.000 description 2
- XHDCVEBAYXPFLR-UHFFFAOYSA-N 1-[[2-(hydroxymethyl)-6-methyl-1H-indol-4-yl]oxy]-3-(propan-2-ylamino)propan-2-ol Chemical compound OC(COC1=C2C=C(NC2=CC(=C1)C)CO)CNC(C)C XHDCVEBAYXPFLR-UHFFFAOYSA-N 0.000 description 2
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 2
- IVEOPBYBMLADDC-UHFFFAOYSA-N 2,6-dimethyl-1h-indole Chemical compound C1=C(C)C=C2NC(C)=CC2=C1 IVEOPBYBMLADDC-UHFFFAOYSA-N 0.000 description 2
- QMUIACTZCYYIHQ-UHFFFAOYSA-N 4-[3-(tert-butylamino)-2-hydroxypropoxy]-6-methyl-1h-indole-2-carboxamide Chemical compound CC1=CC(OCC(O)CNC(C)(C)C)=C2C=C(C(N)=O)NC2=C1 QMUIACTZCYYIHQ-UHFFFAOYSA-N 0.000 description 2
- RCSZVTPWGUPMNJ-UHFFFAOYSA-N 6-methyl-1h-indol-4-ol Chemical compound CC1=CC(O)=C2C=CNC2=C1 RCSZVTPWGUPMNJ-UHFFFAOYSA-N 0.000 description 2
- JMRQMXREZYGXQH-UHFFFAOYSA-N 6-methyl-4-phenylmethoxy-1h-indole-2-carboxamide Chemical compound C=12C=C(C(N)=O)NC2=CC(C)=CC=1OCC1=CC=CC=C1 JMRQMXREZYGXQH-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- GMBFXHCBENERPW-UHFFFAOYSA-N [4-(oxiran-2-ylmethoxy)-1h-indol-6-yl]methyl 2,2-dimethylpropanoate Chemical compound C=12C=CNC2=CC(COC(=O)C(C)(C)C)=CC=1OCC1CO1 GMBFXHCBENERPW-UHFFFAOYSA-N 0.000 description 2
- BSSGAVNTMABXRU-UHFFFAOYSA-N [4-[3-(tert-butylamino)-2-hydroxypropoxy]-1h-indol-2-yl]methyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)NCC(O)COC1=CC=CC2=C1C=C(COC(=O)C(C)(C)C)N2 BSSGAVNTMABXRU-UHFFFAOYSA-N 0.000 description 2
- FLBOUDMKCLTXCM-UHFFFAOYSA-N [4-[3-(tert-butylamino)-2-hydroxypropoxy]-1h-indol-6-yl]methyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)NCC(O)COC1=CC(COC(=O)C(C)(C)C)=CC2=C1C=CN2 FLBOUDMKCLTXCM-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- VBKPXKSWGRDNCO-UHFFFAOYSA-N ethyl 3-(4-methyl-2-nitro-6-phenylmethoxyphenyl)-2-oxopropanoate Chemical compound C1=C(C)C=C([N+]([O-])=O)C(CC(=O)C(=O)OCC)=C1OCC1=CC=CC=C1 VBKPXKSWGRDNCO-UHFFFAOYSA-N 0.000 description 2
- YHDNKDNJPLCIBM-UHFFFAOYSA-N ethyl 4-hydroxy-6-methyl-1h-indole-2-carboxylate Chemical compound C1=C(C)C=C2NC(C(=O)OCC)=CC2=C1O YHDNKDNJPLCIBM-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- YCLHTEHHXRJHKC-UHFFFAOYSA-N methyl 4-hydroxy-1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC(O)=C2C=CNC2=C1 YCLHTEHHXRJHKC-UHFFFAOYSA-N 0.000 description 2
- RTACPLJAQIRNLW-UHFFFAOYSA-N n,n,6-trimethyl-4-(oxiran-2-ylmethoxy)-1h-indole-2-carboxamide Chemical compound C1=C(C)C=C2NC(C(=O)N(C)C)=CC2=C1OCC1CO1 RTACPLJAQIRNLW-UHFFFAOYSA-N 0.000 description 2
- RSDNRJMJBFBIFV-UHFFFAOYSA-N n,n,6-trimethyl-4-phenylmethoxy-1h-indole-2-carboxamide Chemical compound C1=C(C)C=C2NC(C(=O)N(C)C)=CC2=C1OCC1=CC=CC=C1 RSDNRJMJBFBIFV-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- DZUZNEXWAGWFDI-UHFFFAOYSA-N (4-phenylmethoxy-1h-indol-6-yl)methanol Chemical compound C=12C=CNC2=CC(CO)=CC=1OCC1=CC=CC=C1 DZUZNEXWAGWFDI-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- XNEFZCDKZYJWQQ-UHFFFAOYSA-N 1-(1h-indol-4-yloxy)-3-(2-methylsulfanylpropan-2-ylamino)propan-2-ol Chemical compound CSC(C)(C)NCC(O)COC1=CC=CC2=C1C=CN2 XNEFZCDKZYJWQQ-UHFFFAOYSA-N 0.000 description 1
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- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
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- BFEAKHXJJMDHKD-UHFFFAOYSA-N n,n-dimethyl-4-(oxiran-2-ylmethoxy)-1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N(C)C)=CC2=C1OCC1CO1 BFEAKHXJJMDHKD-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
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- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
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- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
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- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
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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
- C07D209/30—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
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
-
- 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
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19742454406 DE2454406A1 (de) | 1974-11-16 | 1974-11-16 | Neue aminopropanol-derivate, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| DE19752505681 DE2505681A1 (de) | 1975-02-11 | 1975-02-11 | Neue aminopropanol-derivate, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| DE19752508251 DE2508251C2 (de) | 1975-02-26 | 1975-02-26 | Derivate des Indols, Verfahren zu deren Herstellung sowie diese enthaltende Arzneimittel |
| DE19752528771 DE2528771A1 (de) | 1975-06-27 | 1975-06-27 | Neue aminopropanol-derivate, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH622248A5 true CH622248A5 ( ) | 1981-03-31 |
Family
ID=27431915
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1473575A CH622248A5 ( ) | 1974-11-16 | 1975-11-13 | |
| CH345680A CH623307A5 ( ) | 1974-11-16 | 1980-05-05 | |
| CH345780A CH623308A5 ( ) | 1974-11-16 | 1980-05-05 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH345680A CH623307A5 ( ) | 1974-11-16 | 1980-05-05 | |
| CH345780A CH623308A5 ( ) | 1974-11-16 | 1980-05-05 |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US4076829A ( ) |
| JP (1) | JPS5845423B2 ( ) |
| AR (3) | AR208570A1 ( ) |
| AT (1) | AT349004B ( ) |
| AU (1) | AU473145B2 ( ) |
| CA (1) | CA1051002A ( ) |
| CH (3) | CH622248A5 ( ) |
| CS (1) | CS199604B2 ( ) |
| DD (1) | DD123460A5 ( ) |
| DK (1) | DK140985C ( ) |
| ES (1) | ES442648A1 ( ) |
| FI (1) | FI61693C ( ) |
| FR (1) | FR2290897A1 ( ) |
| GB (1) | GB1471636A ( ) |
| HU (1) | HU173308B ( ) |
| IE (1) | IE42286B1 ( ) |
| LU (1) | LU73808A1 ( ) |
| NL (1) | NL7513336A ( ) |
| PL (1) | PL100799B1 ( ) |
| SE (1) | SE405598B ( ) |
| SU (2) | SU649314A3 ( ) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2815926A1 (de) * | 1978-04-13 | 1979-10-18 | Boehringer Mannheim Gmbh | Neue carbazolyl-(4)-oxy-propanolamin-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US4314943A (en) * | 1977-07-13 | 1982-02-09 | Mead Johnson & Company | Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols |
| DE2830211A1 (de) * | 1977-07-21 | 1979-02-01 | Sandoz Ag | Substituierte indol-derivate, ihre herstellung und verwendung |
| WO1980000152A1 (en) * | 1978-07-03 | 1980-02-07 | Sandoz Ag | 3-aminopropoxy-aryl derivates,preparation and use thereof |
| US4495352A (en) * | 1979-02-13 | 1985-01-22 | Mead Johnson & Company | Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols |
| EP0025111B1 (en) * | 1979-08-10 | 1984-07-25 | Sandoz Ag | 3-aminopropoxyaryl derivatives, their preparation and pharmaceutical compositions containing them |
| DE3030047A1 (de) * | 1980-08-08 | 1982-03-11 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue aminopropanol-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3115993A1 (de) * | 1981-04-13 | 1982-11-11 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue indol-derivate, verfahren zu ihrer herstellung und pharmazeutische praeparate, die diese verbindungen enthalten |
| US5013732A (en) * | 1984-08-06 | 1991-05-07 | Sterling Drug Inc. | 3-arylcarbonyl- and 3-cycloalkyl-carbonyl-1-aminoalkyl-1H-indoles |
| US5013761A (en) * | 1988-06-03 | 1991-05-07 | Eli Lilly And Company | Serotonin antagonists |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3471515A (en) * | 1965-02-01 | 1969-10-07 | Sandoz Ag | (2-hydroxy-3-substituted aminopropoxy)indoles |
| CH475981A (de) * | 1966-12-13 | 1969-07-31 | Sandoz Ag | Verfahren zur Herstellung neuer Indol-Derivate |
| GB1308029A (en) * | 1969-07-25 | 1973-02-21 | Sandoz Ltd | Indole derivatives |
| BE754360A (fr) * | 1969-08-05 | 1971-02-03 | Sandoz Sa | Nouveaux derives de l'indole, leur preparation et medicaments contenantdes derives |
| US3705907A (en) * | 1970-02-19 | 1972-12-12 | Sandoz Ltd | 4-(2-hydroxy)-3-aminopropoxy)-indole derivatives |
| US3751429A (en) * | 1970-03-24 | 1973-08-07 | Sandoz Ltd | 4-(3-amino-2-substituted propoxy)indole derivatives |
| US3699123A (en) * | 1970-03-24 | 1972-10-17 | Sandoz Ltd | 4-(3-amino-2-hydroxy-propoxy) indole derivatives |
| CH535762A (de) * | 1970-09-30 | 1973-04-15 | Sandoz Ag | Verfahren zur Herstellung neuer Indolderivate |
| CH540253A (de) * | 1971-01-07 | 1973-08-15 | Sandoz Ag | Verfahren zur Herstellung neuer Indole |
-
1975
- 1975-10-28 US US05/626,512 patent/US4076829A/en not_active Expired - Lifetime
- 1975-10-31 GB GB4529975A patent/GB1471636A/en not_active Expired
- 1975-11-13 CH CH1473575A patent/CH622248A5/de not_active IP Right Cessation
- 1975-11-14 FI FI753219A patent/FI61693C/fi not_active IP Right Cessation
- 1975-11-14 NL NL7513336A patent/NL7513336A/xx not_active Application Discontinuation
- 1975-11-14 HU HU75BO1582A patent/HU173308B/hu unknown
- 1975-11-14 LU LU73808A patent/LU73808A1/xx unknown
- 1975-11-14 AT AT870975A patent/AT349004B/de not_active IP Right Cessation
- 1975-11-14 CA CA239,645A patent/CA1051002A/en not_active Expired
- 1975-11-14 DK DK513575A patent/DK140985C/da active
- 1975-11-14 DD DD189466A patent/DD123460A5/xx unknown
- 1975-11-14 AR AR261214A patent/AR208570A1/es active
- 1975-11-14 SE SE7512823A patent/SE405598B/xx unknown
- 1975-11-14 FR FR7534782A patent/FR2290897A1/fr active Granted
- 1975-11-14 IE IE2476/75A patent/IE42286B1/en unknown
- 1975-11-14 ES ES442648A patent/ES442648A1/es not_active Expired
- 1975-11-14 JP JP50137692A patent/JPS5845423B2/ja not_active Expired
- 1975-11-14 CS CS757720A patent/CS199604B2/cs unknown
- 1975-11-14 SU SU752189622A patent/SU649314A3/ru active
- 1975-11-15 PL PL1975184778A patent/PL100799B1/pl unknown
- 1975-11-17 AU AU86692/75A patent/AU473145B2/en not_active Expired
-
1976
- 1976-05-31 AR AR263461A patent/AR211268A1/es active
- 1976-05-31 AR AR263462A patent/AR213287A1/es active
- 1976-07-19 SU SU762383853A patent/SU679135A3/ru active
-
1978
- 1978-09-18 US US05/943,512 patent/US4229464A/en not_active Expired - Lifetime
-
1980
- 1980-05-05 CH CH345680A patent/CH623307A5/de not_active IP Right Cessation
- 1980-05-05 CH CH345780A patent/CH623308A5/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| LU73808A1 ( ) | 1976-06-11 |
| AU8669275A (en) | 1976-06-17 |
| CH623308A5 ( ) | 1981-05-29 |
| PL100799B1 (pl) | 1978-11-30 |
| DK140985B (da) | 1979-12-17 |
| CS199604B2 (en) | 1980-07-31 |
| CA1051002A (en) | 1979-03-20 |
| FI61693C (fi) | 1982-09-10 |
| NL7513336A (nl) | 1976-05-18 |
| DK140985C (da) | 1980-06-02 |
| DD123460A5 ( ) | 1976-12-20 |
| US4229464A (en) | 1980-10-21 |
| AU473145B2 (en) | 1976-06-17 |
| IE42286B1 (en) | 1980-07-16 |
| FR2290897B1 ( ) | 1978-11-10 |
| AT349004B (de) | 1979-03-12 |
| ATA870975A (de) | 1978-08-15 |
| JPS5845423B2 (ja) | 1983-10-08 |
| IE42286L (en) | 1976-05-16 |
| ES442648A1 (es) | 1977-04-16 |
| GB1471636A (en) | 1977-04-27 |
| AR213287A1 (es) | 1979-01-15 |
| SU649314A3 (ru) | 1979-02-25 |
| SE405598B (sv) | 1978-12-18 |
| HU173308B (hu) | 1979-04-28 |
| AR208570A1 (es) | 1977-02-15 |
| JPS5175059A ( ) | 1976-06-29 |
| DK513575A (da) | 1976-05-17 |
| SU679135A3 (ru) | 1979-08-05 |
| AR211268A1 (es) | 1977-11-15 |
| SE7512823L (sv) | 1976-05-17 |
| CH623307A5 ( ) | 1981-05-29 |
| US4076829A (en) | 1978-02-28 |
| FI753219A ( ) | 1976-05-17 |
| FR2290897A1 (fr) | 1976-06-11 |
| FI61693B (fi) | 1982-05-31 |
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| Date | Code | Title | Description |
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| PL | Patent ceased | ||
| PL | Patent ceased |