反应详情

温度

80 °C

A mixture of 5-(pyridin-4-yl)-1H-indole (17.2 g, 0.089 mol), 1-[(S)-3-(2-bromoethyl)-2,3-dihydro-1H-indol-1-yl]-ethanone (28.5 g, 0.11 mol), 1,4-dioxane (900 mL), tetrahydrofuran (150 mL) and methanol (100 mL) was heated under reflux at approximately 80° C. for 68 h. The mixture was cooled, and the solid formed was collected by filtration and washed with tetrahydrofuran. The compound was dried in vacuo to give 1-[2-((S)-1-acetyl-2,3-dihydro-1H-indol-3-yl)ethyl]-4-(1H-indol-5-yl)pyridinium bromide (27.5 g, 64%), which was suspended in methanol (900 mL) and cooled (5° C.). To this mixture was added sodium borohydride (6.75 g, 0.18 mol) over a period of 20 min. The resulting mixture was stirred at 10° C. for 1 h and concentrated to about 200 mL. The mixture was poured onto a mixture of brine (750 mL) and 28% aqueous sodium hydroxide (20 mL), and the aqueous phase was extracted with a mixture of ethyl acetate and tetrahydrofuran. The combined organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (ethyl acetate/tetrahydrofuran/triethylamine 70:25:5) to give 1-((S)-3-{2-[4-(1H-indol-5-yl)-3,6-dihydro-2H-piperidin-1-yl]ethyl}-2,3-dihydro-1H-indol-1-yl)-ethanone (20.5 g, 85%). This compound (8.0 g, 0.02 mol) was dissolved in 1-propanol (220 mL) and heated to 60° C. To this mixture was added 28% aqueous sodium hydroxide, and the resulting mixture was boiled under reflux for 7 h. The mixture was cooled and poured onto brine. The aqueous phase was extracted with a mixture of ethyl acetate and tetrahydrofuran, and the combined organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was combined with a residue coming from another experiment starting from 1 g of 1-((S)-3-{2-[4-(1H-indol-5-yl)-3,6-dihydro-2H-piperidin-1-yl]ethyl}-2,3-dihydro-1H-indol-1-yl)-ethanone. The combined residue was purified by flash chromatography (ethyl acetate/triethylamine 95:5) to give the title compound (4.95 g).

1. temperaturewas heated
2. temperatureThe mixture was cooled
3. customthe solid formed
4. filtrationwas collected by filtration
5. washwashed with tetrahydrofuran
6. customThe compound was dried in vacuo