2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled (−78° C.) solution of 2.67 g (9.20 mmol) 5-bromo-1-(4-fluorophenyl)-1H-indazole in 10 mL of anhydrous THF was added 7.36 mL (18.40 mmol) of a 2.5 M solution of n-butyllithium in hexane followed by a solution of 1.00 g (4.69 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone in 5 mL of THF in one portion. The reaction was then stirred at −78° C. for 30 minutes and quenched with 5 mL of water. The mixture was warmed to room temperature and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (20%-40% ethyl acetate in hexanes). The major fractions were combined and concentrated to afford 978 mg of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-indol-3-yl)ethanol. MS m/z 426.39 (MIT). quenched with 5 mL of water The mixture was warmed to room temperature extracted with ethyl acetate The combined organic layer was washed with brine dried over sodium sulfate concentrated in vacuo The residue was purified by flash chromatography (20%-40% ethyl acetate in hexanes) concentrated

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled (−78° C.) solution of 2.67 g (9.20 mmol) 5-bromo-1-(4-fluorophenyl)-1H-indazole in 10 mL of anhydrous THF was added 7.36 mL (18.40 mmol) of a 2.5 M solution of n-butyllithium in hexane followed by a solution of 1.00 g (4.69 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone in 5 mL of THF in one portion. The reaction was then stirred at −78° C. for 30 minutes and quenched with 5 mL of water. The mixture was warmed to room temperature and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (20%-40% ethyl acetate in hexanes). The major fractions were combined and concentrated to afford 978 mg of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-indol-3-yl)ethanol. MS m/z 426.39 (MIT). quenched with 5 mL of water The mixture was warmed to room temperature extracted with ethyl acetate The combined organic layer was washed with brine dried over sodium sulfate concentrated in vacuo The residue was purified by flash chromatography (20%-40% ethyl acetate in hexanes) concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled (−78° C.) solution of 241 mg (1.13 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone in 5 mL of anhydrous THF was added 45 mg (1.13 mmol) of 60% NaH in mineral oil. In another flask, 452 μL (1.13 mmol) of n-BuLi was then added to a chilled (−78° C.) solution of 310 mg (1.13 mmol) of 5-bromo-1-pyridin-3-yl-1H-indazole in 10 mL of THF. After 1 minute, the sodium salt of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone was added to the indazole anion via a cannula. After 1 hour, the mixture was diluted with 25 mL of saturated aqueous ammonium chloride and extracted with three 15 mL portions of ethyl acetate. The combined organic layers were washed with three 10 mL portions of brine, dried over magnesium sulfate, filtered and concentrated. The crude material was purified using Combiflash chromatography using EtOAc-hexanes (0-70% gradient) to afford 45 mg (10%) of 2,2,2-trifluoro-1-(1H-indol-3-yl)-1-(1-pyridin-3-yl-1H-indazol-5-yl)ethanol as a colorless solid. After 1 hour extracted with three 15 mL portions of ethyl acetate The combined organic layers were washed with three 10 mL portions of brine dried over magnesium sulfate filtered concentrated The crude material was purified

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled (−78° C.) solution of 241 mg (1.13 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone in 5 mL of anhydrous THF was added 45 mg (1.13 mmol) of 60% NaH in mineral oil. In another flask, 452 μL (1.13 mmol) of n-BuLi was then added to a chilled (−78° C.) solution of 310 mg (1.13 mmol) of 5-bromo-1-pyridin-3-yl-1H-indazole in 10 mL of THF. After 1 minute, the sodium salt of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone was added to the indazole anion via a cannula. After 1 hour, the mixture was diluted with 25 mL of saturated aqueous ammonium chloride and extracted with three 15 mL portions of ethyl acetate. The combined organic layers were washed with three 10 mL portions of brine, dried over magnesium sulfate, filtered and concentrated. The crude material was purified using Combiflash chromatography using EtOAc-hexanes (0-70% gradient) to afford 45 mg (10%) of 2,2,2-trifluoro-1-(1H-indol-3-yl)-1-(1-pyridin-3-yl-1H-indazol-5-yl)ethanol as a colorless solid. After 1 hour extracted with three 15 mL portions of ethyl acetate The combined organic layers were washed with three 10 mL portions of brine dried over magnesium sulfate filtered concentrated The crude material was purified

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled (−78° C.) solution of 2.67 g (9.20 mmol) 5-bromo-1-(4-fluorophenyl)-1H-indazole in 10 mL of anhydrous THF was added 7.36 mL (18.40 mmol) of a 2.5 M solution of n-butyllithium in hexane followed by a solution of 1.00 g (4.69 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone in 5 mL of THF in one portion. The reaction was then stirred at −78° C. for 30 minutes and quenched with 5 mL of water. The mixture was warmed to room temperature and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (20%-40% ethyl acetate in hexanes). The major fractions were combined and concentrated to afford 978 mg of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-indol-3-yl)ethanol. MS m/z 426.39 (MIT). quenched with 5 mL of water The mixture was warmed to room temperature extracted with ethyl acetate The combined organic layer was washed with brine dried over sodium sulfate concentrated in vacuo The residue was purified by flash chromatography (20%-40% ethyl acetate in hexanes) concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled (−78° C.) solution of 241 mg (1.13 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone in 5 mL of anhydrous THF was added 45 mg (1.13 mmol) of 60% NaH in mineral oil. In another flask, 452 μL (1.13 mmol) of n-BuLi was then added to a chilled (−78° C.) solution of 310 mg (1.13 mmol) of 5-bromo-1-pyridin-3-yl-1H-indazole in 10 mL of THF. After 1 minute, the sodium salt of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone was added to the indazole anion via a cannula. After 1 hour, the mixture was diluted with 25 mL of saturated aqueous ammonium chloride and extracted with three 15 mL portions of ethyl acetate. The combined organic layers were washed with three 10 mL portions of brine, dried over magnesium sulfate, filtered and concentrated. The crude material was purified using Combiflash chromatography using EtOAc-hexanes (0-70% gradient) to afford 45 mg (10%) of 2,2,2-trifluoro-1-(1H-indol-3-yl)-1-(1-pyridin-3-yl-1H-indazol-5-yl)ethanol as a colorless solid. After 1 hour extracted with three 15 mL portions of ethyl acetate The combined organic layers were washed with three 10 mL portions of brine dried over magnesium sulfate filtered concentrated The crude material was purified

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The mixture of 4.80 g of 3-(trifluoroacetyl)-1H-indole, 1.35 g of paraformaldehyde and 0.10 g of triethylamine was stirred at 130° C. for 2 hours. After the reaction mixture was cooled to room temperature, acetone was added to the reaction mixture. The mixture was filtered, and then the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and hexane was added to the residue, as a result, a crystal was formed. The crystal was collected to obtain 5.36 g of 3-(trifluoroacetyl)-1H-indole-1-ylmethanol. After the reaction mixture was cooled to room temperature The mixture was filtered the filtrate was concentrated under reduced pressure was added to the residue, as a result a crystal was formed The crystal was collected

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: was prepared from 2,2,2-trifluoro-1-(1H-indol-3-yl)-ethanone in a similar manner as described in Scheme A13 (step B and C) for the preparation of (3-acetyl-5-trifluoromethoxy-indol-1-yl)-acetic acid. White solid. MS: 272.0 [M+H]+; tR (HPLC conditions c): 4.59 min. 4.59 min.

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled (−78° C.) solution of 2.67 g (9.20 mmol) 5-bromo-1-(4-fluorophenyl)-1H-indazole in 10 mL of anhydrous THF was added 7.36 mL (18.40 mmol) of a 2.5 M solution of n-butyllithium in hexane followed by a solution of 1.00 g (4.69 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone in 5 mL of THF in one portion. The reaction was then stirred at −78° C. for 30 minutes and quenched with 5 mL of water. The mixture was warmed to room temperature and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (20%-40% ethyl acetate in hexanes). The major fractions were combined and concentrated to afford 978 mg of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-indol-3-yl)ethanol. MS m/z 426.39 (MIT). quenched with 5 mL of water The mixture was warmed to room temperature extracted with ethyl acetate The combined organic layer was washed with brine dried over sodium sulfate concentrated in vacuo The residue was purified by flash chromatography (20%-40% ethyl acetate in hexanes) concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a chilled (−78° C.) solution of 241 mg (1.13 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone in 5 mL of anhydrous THF was added 45 mg (1.13 mmol) of 60% NaH in mineral oil. In another flask, 452 μL (1.13 mmol) of n-BuLi was then added to a chilled (−78° C.) solution of 310 mg (1.13 mmol) of 5-bromo-1-pyridin-3-yl-1H-indazole in 10 mL of THF. After 1 minute, the sodium salt of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone was added to the indazole anion via a cannula. After 1 hour, the mixture was diluted with 25 mL of saturated aqueous ammonium chloride and extracted with three 15 mL portions of ethyl acetate. The combined organic layers were washed with three 10 mL portions of brine, dried over magnesium sulfate, filtered and concentrated. The crude material was purified using Combiflash chromatography using EtOAc-hexanes (0-70% gradient) to afford 45 mg (10%) of 2,2,2-trifluoro-1-(1H-indol-3-yl)-1-(1-pyridin-3-yl-1H-indazol-5-yl)ethanol as a colorless solid. After 1 hour extracted with three 15 mL portions of ethyl acetate The combined organic layers were washed with three 10 mL portions of brine dried over magnesium sulfate filtered concentrated The crude material was purified