2-propan-2-yl-1H-indole

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: POCl3 (0.86 ml, 9.4 mmol) was added dropwise to anhydrous DMF (4 ml) at 0° C. with stirring. After 30 min, this solution was added dropwise to a solution of 2-isopropyl-1H-indole (Compound 38, 1.24 g, 7.8 mmol) in DMF (16 ml) at 0° C. under argon. The reaction was stirred for 1 h while it warmed up to room temperature. The reaction was diluted with EtOAc, washed with aq. NaHCO3, brine, dried over Na2SO4, and concentrated in vacuo. The residual solid was washed with Et2O to yield 2-isopropyl-1H-indole-3-carbaldehyde (Compound 39) as a beige solid. The reaction was stirred for 1 h while it washed with aq. NaHCO3, brine dried over Na2SO4 concentrated in vacuo The residual solid was washed with Et2O

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(3-methylbut-1-ynyl)aniline (Compound 37, 3.47 g, 21.8 mmol) in DMF (100 ml) was added copper (I) iodide (41 mg, 0.22 mmol). The mixture was stirred at 160° C. for 2 h and was concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with 5% EtOAc-hexanes to yield 2-isopropyl-1H-indole (Compound 38) as an off-white solid. was concentrated in vacuo The residue was purified by flash chromatography on silica gel eluting with 5% EtOAc-hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: POCl3 (0.86 ml, 9.4 mmol) was added dropwise to anhydrous DMF (4 ml) at 0° C. with stirring. After 30 min, this solution was added dropwise to a solution of 2-isopropyl-1H-indole (Compound 38, 1.24 g, 7.8 mmol) in DMF (16 ml) at 0° C. under argon. The reaction was stirred for 1 h while it warmed up to room temperature. The reaction was diluted with EtOAc, washed with aq. NaHCO3, brine, dried over Na2SO4, and concentrated in vacuo. The residual solid was washed with Et2O to yield 2-isopropyl-1H-indole-3-carbaldehyde (Compound 39) as a beige solid. The reaction was stirred for 1 h while it washed with aq. NaHCO3, brine dried over Na2SO4 concentrated in vacuo The residual solid was washed with Et2O

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: POCl3 (0.86 ml, 9.4 mmol) was added dropwise to anhydrous DMF (4 ml) at 0° C. with stirring. After 30 min, this solution was added dropwise to a solution of 2-isopropyl-1H-indole (Compound 38, 1.24 g, 7.8 mmol) in DMF (16 ml) at 0° C. under argon. The reaction was stirred for 1 h while it warmed up to room temperature. The reaction was diluted with EtOAc, washed with aq. NaHCO3, brine, dried over Na2SO4, and concentrated in vacuo. The residual solid was washed with Et2O to yield 2-isopropyl-1H-indole-3-carbaldehyde (Compound 39) as a beige solid. The reaction was stirred for 1 h while it washed with aq. NaHCO3, brine dried over Na2SO4 concentrated in vacuo The residual solid was washed with Et2O

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(3-methylbut-1-ynyl)aniline (Compound 37, 3.47 g, 21.8 mmol) in DMF (100 ml) was added copper (I) iodide (41 mg, 0.22 mmol). The mixture was stirred at 160° C. for 2 h and was concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with 5% EtOAc-hexanes to yield 2-isopropyl-1H-indole (Compound 38) as an off-white solid. was concentrated in vacuo The residue was purified by flash chromatography on silica gel eluting with 5% EtOAc-hexanes

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4.65 g of sodium cyanoborohydride are gradually added to a solution of 5.0 g of 2-isopropylindole in 50 ml of acetic acid under argon cooled to a temperature of about 15° C. The reaction mixture is stirred at a temperature of about 15° C. for 2 hours and is then treated with 25 ml of water. It is then cooled to a temperature of about 5° C. and alkalinized by gradual addition of powdered sodium hydroxide. The reaction mixture is allowed to warm up to ambient temperature and is then stirred for 16 hours. The precipitate is filtered off through sintered glass and washed with 50 ml of water and then 50 ml of ethyl acetate. The filtrate is diluted with 50 ml of water and 70 ml of ethyl acetate and then separated by settling out. The organic phase is separated and the aqueous phase is extracted with 2×100 ml of ethyl acetate. The organic phases are combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 90 g cartridge of 15-40 μm silica, elution being carried out with a 95/5 v/v cyclohexane/ethyl acetate mixture, at a flow rate of 50 ml/min. 4.0 g of (±)-2-isopropylindoline are thus obtained in the form of a colorless oil which crystallizes into a white solid, the characteristics of which are the following: It is then cooled to a temperature of about 5° C. to warm up to ambient temperature is then stirred for 16 hours The precipitate is filtered off through sintered glass washed with 50 ml of water The filtrate is diluted with 50 ml of water and 70 ml of ethyl acetate separated The organic phase is separated the aqueous phase is extracted with 2×100 ml of ethyl acetate washed with saturated brine dried over anhydrous magnesium sulfate filtered concentrated to dryness under reduced pressure The residue is purified by chromatography on a 90 g cartridge of 15-40 μm silica, elution

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a well-stirred solution of 2-isopropylindole (9.9 g.) in ethanol (30 ml.) at 0° C., there was added a 33% (w./w.) solution of dimethylamine in ethanol (10 ml.) and glacial acetic acid (3.5 ml.). A solution of 40% (w./v.) aqueous formaldehyde (5 ml.) was then added dropwise to the mixture, and the resulting solution was stirred at 5° C. for a period of one hour. Ice/water was next added to the reaction mixture, followed by excess solid potassium carbonate to give an orange oil. The liquid was then repeatedly extracted with diethyl ether (three times), using 50 ml. portions for each extraction. The combined ethereal extracts were then dried over anhydrous sodium sulfate and evaporated to give crude 3-(dimethylaminomethyl)-2-isopropylindole (4.5 g.) as a brown oil. The latter substance was used directly in Example I (as a starting material) without any further purification being necessary. to give an orange oil The liquid was then repeatedly extracted with diethyl ether (three times) portions for each extraction The combined ethereal extracts were then dried over anhydrous sodium sulfate evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: POCl3 (0.86 ml, 9.4 mmol) was added dropwise to anhydrous DMF (4 ml) at 0° C. with stirring. After 30 min, this solution was added dropwise to a solution of 2-isopropyl-1H-indole (Compound 38, 1.24 g, 7.8 mmol) in DMF (16 ml) at 0° C. under argon. The reaction was stirred for 1 h while it warmed up to room temperature. The reaction was diluted with EtOAc, washed with aq. NaHCO3, brine, dried over Na2SO4, and concentrated in vacuo. The residual solid was washed with Et2O to yield 2-isopropyl-1H-indole-3-carbaldehyde (Compound 39) as a beige solid. The reaction was stirred for 1 h while it washed with aq. NaHCO3, brine dried over Na2SO4 concentrated in vacuo The residual solid was washed with Et2O

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(3-methylbut-1-ynyl)aniline (Compound 37, 3.47 g, 21.8 mmol) in DMF (100 ml) was added copper (I) iodide (41 mg, 0.22 mmol). The mixture was stirred at 160° C. for 2 h and was concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with 5% EtOAc-hexanes to yield 2-isopropyl-1H-indole (Compound 38) as an off-white solid. was concentrated in vacuo The residue was purified by flash chromatography on silica gel eluting with 5% EtOAc-hexanes