* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With potassium carbonate In acetone at 50℃; for 96 h;
E1. 5-Ethoxy-indole; A mixture of commercially available 5-hydroxy-indole (18 g, 13.5 mmol), anhydrous K2CO3 (93.5 g, 5 equiv) and iodoethane (40.5 ml, 3.75 equiv) in acetone (180 ml_) is stirred at 50 0C under argon. When TLC (dichloromethane-methanol, 95:5) indicates the disappearance of 5-hydroxy-indole (4 days), the mixture is filtered, the solid is washed with acetone, then the filtrate is concentrated to give 17.67 g (90 percent) of the title compound, which is sufficiently pure to be used in the next step. M. p. 144-146 0C (from ethanol).
90%
With potassium carbonate In acetone at 50℃; for 96 h;
A mixture of commercially available 5-hydroxy-indole (18 g, 13.5 mmol), anhydrous K2CO3 (93.5 g, 5 equiv) and iodoethane (40.5 ml, 3.75 equiv) in acetone (180 ml_) is stirred at 50 0C under argon. When TLC (dichloromethane-methanol, 95:5) indicates the disappearance of 5-hydroxy- indole (4 days), the mixture is filtered, the solid is washed with acetone, then the filtrate is concentrated to give 17.67 g (90 percent) of the title compound, which is sufficiently pure to be used in the next step. M. p. 144-146 0C (from ethanol).
90%
With potassium carbonate In acetone at 50℃; for 96 h;
A mixture of commercially available 5-hydroxy-indole (18 g, 13.5 mmol), anhydrous K2CO3 (93.5 g, 5 equiv) and iodoethane (40.5 ml, 3.75 equiv) in acetone (180 mL) is stirred at 50 0C under argon. When TLC (dichloromethane-methanol, 95:5 v.v) indicates the disappearance of 5-hydroxy-indole (4 days), the mixture is filtered, the solid is washed with acetone, then the filtrate is concentrated to give 17.67 g (90 percent) of the title compound, which is sufficiently pure to be used in the next step. M. p. 144-1460C (from ethanol).
D2. (5-Ethoxy-1 H-indol-3-ylmethyl)-dimethyl-amine; A mixture of <strong>[10501-17-4]5-ethoxy-indole</strong> (7.84 g, 48.7 mmol), 40% aqueous dimethylamine (9.25 ml, 73 mmol, 1.5 equiv), and 96% acetic acid (30 ml) is stirred at 0 0C, then 36% aqueous formaldehyde solution (6.33 ml, 82.7 mmol, 1.7 equiv) is added drop wise. The mixture is allowed to come to room temperature, and after stirring overnight TLC (dichloromethane-methanol, 4:1 ) indicates the absence of starting material. 10% Aqueous NaOH (150 ml) is added and the mixture is stirred at room temperature for 2 h. It is then extracted with dichloromethane (4 x 200 ml), the organic layer is dried and concentrated. The residue is purified by column chromatography (dichloromethane-methanol, 4:1 - > methanol- aqueous ammonia 50:1 ) to give crude product (10.18 g, 96 %), which is crystallized from acetone to provide pure (5-ethoxy-1 H-indol-ylmethyl)-dimethyl-amine (10.2 g, 96 %) as white crystals. M. p. 95-97 0C.
96%
A mixture of <strong>[10501-17-4]5-ethoxy-indole</strong> (7.84 g, 48.7 mmol), 40% aqueous dimethylamine (9.25 ml, 73 mmol, 1.5 equiv), and 96% acetic acid (30 ml) is stirred at 0 0C, then 36% aqueous formaldehyde solution (6.33 ml, 82.7 mmol, 1.7 equiv) is added drop wise. The mixture is allowed to come to room temperature, and after stirring overnight TLC (dichloromethane-methanol, 4:1 ) indicates the absence of starting material. 10% Aqueous NaOH (150 ml) is added and the mixture is stirred at room temperature for 2 h. It is then extracted with dichloromethane (4 x 200 ml), the organic layer is dried and concentrated. The residue is purified by column chromatography (dichloromethane- methanol, 4:1 - > methanol-aqueous ammonia 50:1 ) to give crude product (10.18 g, 96 %), which is crystallized from acetone to provide pure (5-ethoxy-1 H-indol-ylmethyl)-dimethyl-amine (10.2 g, 96 %) as white crystals. M. p. 95-97 0C.
96%
A mixture of <strong>[10501-17-4]5-ethoxy-indole</strong> (7.84 g, 48.7 mmo.), 40% aqueous dimethylamine (9.25 ml, 73 mmol, 1.5 equiv), and 96% acetic acid (30 ml) is stirred at 0 0C, then 36% aqueous formaldehyde solution (6.33 ml, 82.7 mmol, 1.7 equiv) is added drop wise. The mixture is allowed to come to room temperature, and after stirring overnight TLC (dichloromethane-metha?ol, 4:1 ) indicates the absence of stariing material. 10% Aqueous NaOH (150 ml) is added and the mixture is stirred at room temperature for 2 h. It is then extracted with dichloromethane (4 x 200 ml), the organic layer is dried and concentrated. The residue is purified by column chromatography (dichloromethane-methanol, 4:1 v:v ? methanol- aqueous ammonia 50:1 v:v) to give crude product (10.18 g, 96 %), which is crystallized from acetone to provide pure (5-ethoxy-1H-indol-ylmethyl)-dimethyl-amine (10.2 g, 96 %) as white crystals. M.p. 95- 97 0C.
With potassium carbonate; In acetone; at 50℃; for 96h;
E1. 5-Ethoxy-indole; A mixture of commercially available 5-hydroxy-indole (18 g, 13.5 mmol), anhydrous K2CO3 (93.5 g, 5 equiv) and iodoethane (40.5 ml, 3.75 equiv) in acetone (180 ml_) is stirred at 50 0C under argon. When TLC (dichloromethane-methanol, 95:5) indicates the disappearance of 5-hydroxy-indole (4 days), the mixture is filtered, the solid is washed with acetone, then the filtrate is concentrated to give 17.67 g (90 %) of the title compound, which is sufficiently pure to be used in the next step. M. p. 144-146 0C (from ethanol).
90%
With potassium carbonate; In acetone; at 50℃; for 96h;
A mixture of commercially available 5-hydroxy-indole (18 g, 13.5 mmol), anhydrous K2CO3 (93.5 g, 5 equiv) and iodoethane (40.5 ml, 3.75 equiv) in acetone (180 ml_) is stirred at 50 0C under argon. When TLC (dichloromethane-methanol, 95:5) indicates the disappearance of 5-hydroxy- indole (4 days), the mixture is filtered, the solid is washed with acetone, then the filtrate is concentrated to give 17.67 g (90 %) of the title compound, which is sufficiently pure to be used in the next step. M. p. 144-146 0C (from ethanol).
90%
With potassium carbonate; In acetone; at 50℃; for 96h;
A mixture of commercially available 5-hydroxy-indole (18 g, 13.5 mmol), anhydrous K2CO3 (93.5 g, 5 equiv) and iodoethane (40.5 ml, 3.75 equiv) in acetone (180 mL) is stirred at 50 0C under argon. When TLC (dichloromethane-methanol, 95:5 v.v) indicates the disappearance of 5-hydroxy-indole (4 days), the mixture is filtered, the solid is washed with acetone, then the filtrate is concentrated to give 17.67 g (90 %) of the title compound, which is sufficiently pure to be used in the next step. M. p. 144-1460C (from ethanol).
General procedure: Methyl iodide (4.8 ml, 77.7 mmoles) was added to a suspension of magnesium turnings (1.5 g, 62.5 mmoles) in tetrahydrofuran (35 ml). After stirring for 30 minutes at 25 - 30 oC under nitrogen atmosphere, indole (7 g, 59.8 mmoles) dissolved in tetrahydrofuran (15 ml) was added to the reaction mixture. The reaction mass was further stirred for 1 hr at 25 - 30 oC. A solution of 1-methyl-pyrrole-2,5-dione (6.7 g, 60.3 mmoles) in toluene (20 ml) was added to the above reaction mass and the resulting mass was further stirred for 3 hrs at 70 C. The progress of the reaction was monitored by TLC. After completion of reaction, the mass was cooled to 25-30 C and poured on to an aqueous solution (20 % w/v, 100 mL) of citric acid. The product was extracted with ethyl acetate (3 x 75 ml), the combined organic layers were washed with brine (50 ml) and dried over anhydrous sodium sulfate. Organic volatiles were removed under reduced pressure and resulting crude product was chromatographed (ethyl acetate: n-Hexane (1:1)) to obtain 3-(1H-indol-3-yl)-1-methyl pyrrolidine-2,5-dione ( 8.9 g, 65 %).
General procedure: Methyl iodide (4.8 ml, 77.7 mmoles) was added to a suspension of magnesium turnings (1.5 g, 62.5 mmoles) in tetrahydrofuran (35 ml). After stirring for 30 minutes at 25 - 30 oC under nitrogen atmosphere, indole (7 g, 59.8 mmoles) dissolved in tetrahydrofuran (15 ml) was added to the reaction mixture. The reaction mass was further stirred for 1 hr at 25 - 30 oC. A solution of 1-methyl-pyrrole-2,5-dione (6.7 g, 60.3 mmoles) in toluene (20 ml) was added to the above reaction mass and the resulting mass was further stirred for 3 hrs at 70 C. The progress of the reaction was monitored by TLC. After completion of reaction, the mass was cooled to 25-30 C and poured on to an aqueous solution (20 % w/v, 100 mL) of citric acid. The product was extracted with ethyl acetate (3 x 75 ml), the combined organic layers were washed with brine (50 ml) and dried over anhydrous sodium sulfate. Organic volatiles were removed under reduced pressure and resulting crude product was chromatographed (ethyl acetate: n-Hexane (1:1)) to obtain 3-(1H-indol-3-yl)-1-methyl pyrrolidine-2,5-dione ( 8.9 g, 65 %).
General procedure: Methyl iodide (4.8 ml, 77.7 mmoles) was added to a suspension of magnesium turnings (1.5 g, 62.5 mmoles) in tetrahydrofuran (35 ml). After stirring for 30 minutes at 25 - 30 oC under nitrogen atmosphere, indole (7 g, 59.8 mmoles) dissolved in tetrahydrofuran (15 ml) was added to the reaction mixture. The reaction mass was further stirred for 1 hr at 25 - 30 oC. A solution of 1-methyl-pyrrole-2,5-dione (6.7 g, 60.3 mmoles) in toluene (20 ml) was added to the above reaction mass and the resulting mass was further stirred for 3 hrs at 70 C. The progress of the reaction was monitored by TLC. After completion of reaction, the mass was cooled to 25-30 C and poured on to an aqueous solution (20 % w/v, 100 mL) of citric acid. The product was extracted with ethyl acetate (3 x 75 ml), the combined organic layers were washed with brine (50 ml) and dried over anhydrous sodium sulfate. Organic volatiles were removed under reduced pressure and resulting crude product was chromatographed (ethyl acetate: n-Hexane (1:1)) to obtain 3-(1H-indol-3-yl)-1-methyl pyrrolidine-2,5-dione ( 8.9 g, 65 %).
5-ethoxy-3-(1-(furan-2-ylmethyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66%
With potassium hydroxide; In methanol; at 75℃; for 18h;Sealed tube;
General procedure: A 20mL vial was charged with 1 mmol of indole, 1.1 mmol of Nsubstituted4-piperidone and 5mL of 1M KOH in MeOH. The vialwas sealed and the reaction was stirred at 75 C 18 h. If precipitateappeared after cooling to room temperature it was filtered andwashed with water and diethyl ether and dried. Otherwise, thereaction was stripped of solvent and remaining residue partitionedbetween water and DCM. Aqueous was extracted with DCM andcombined organics washed with brine, dried with anhydrousmagnesium sulfate and the crude product was purified by flashcolumn chromatography.
5-ethoxy-3-(1-(thiophen-2-ylmethyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66%
With potassium hydroxide; In methanol; at 75℃; for 18h;Sealed tube;
General procedure: A 20mL vial was charged with 1 mmol of indole, 1.1 mmol of Nsubstituted4-piperidone and 5mL of 1M KOH in MeOH. The vialwas sealed and the reaction was stirred at 75 C 18 h. If precipitateappeared after cooling to room temperature it was filtered andwashed with water and diethyl ether and dried. Otherwise, thereaction was stripped of solvent and remaining residue partitionedbetween water and DCM. Aqueous was extracted with DCM andcombined organics washed with brine, dried with anhydrousmagnesium sulfate and the crude product was purified by flashcolumn chromatography.
3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-5-ethoxy-1H-indole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
46%
With potassium hydroxide; In methanol; at 75℃; for 18h;Sealed tube;
General procedure: A 20mL vial was charged with 1 mmol of indole, 1.1 mmol of Nsubstituted4-piperidone and 5mL of 1M KOH in MeOH. The vialwas sealed and the reaction was stirred at 75 C 18 h. If precipitateappeared after cooling to room temperature it was filtered andwashed with water and diethyl ether and dried. Otherwise, thereaction was stripped of solvent and remaining residue partitionedbetween water and DCM. Aqueous was extracted with DCM andcombined organics washed with brine, dried with anhydrousmagnesium sulfate and the crude product was purified by flashcolumn chromatography.
5-ethoxy-3-(1-(4-methoxybenzyl)-1,2,3,6 -tetrahydropyridin-4-yl)-1H-indole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
30%
With potassium hydroxide; In methanol; at 75℃; for 18h;Sealed tube;
General procedure: A 20mL vial was charged with 1 mmol of indole, 1.1 mmol of Nsubstituted4-piperidone and 5mL of 1M KOH in MeOH. The vialwas sealed and the reaction was stirred at 75 C 18 h. If precipitateappeared after cooling to room temperature it was filtered andwashed with water and diethyl ether and dried. Otherwise, thereaction was stripped of solvent and remaining residue partitionedbetween water and DCM. Aqueous was extracted with DCM andcombined organics washed with brine, dried with anhydrousmagnesium sulfate and the crude product was purified by flashcolumn chromatography.
5-ethoxy-3-(1-(3-methoxybenzyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
With potassium hydroxide; In methanol; at 75℃; for 18h;Sealed tube;
General procedure: A 20mL vial was charged with 1 mmol of indole, 1.1 mmol of Nsubstituted4-piperidone and 5mL of 1M KOH in MeOH. The vialwas sealed and the reaction was stirred at 75 C 18 h. If precipitateappeared after cooling to room temperature it was filtered andwashed with water and diethyl ether and dried. Otherwise, thereaction was stripped of solvent and remaining residue partitionedbetween water and DCM. Aqueous was extracted with DCM andcombined organics washed with brine, dried with anhydrousmagnesium sulfate and the crude product was purified by flashcolumn chromatography.