5-bromo-3-(2-pyrrolidin-1-ylethyl)-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:

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

Procedure: To a solution of 5-bromo-3-(2-pyrrolidinylethyl)-1H-indole (Example 2, 9.10 g, 31 mmol) in tetrahydrofuran (100 mL) cooled to 0° C., were added sodium hydride (12.4 g, 310 mmol) and p-toluenesulfonyl chloride (6.10 g, 32 mmol). The resulting mixture was stirred at room temperature for 3 h, poured into water (200 mL) and extracted into ethyl acetate (200 mL). The organic phase was washed with water (200 mL) and then poured onto a silica gel column which was eluted with ethyl acetate followed by methanol. The title compound was obtained as a yellow syrup (11.7 g, 90%). extracted into ethyl acetate (200 mL) The organic phase was washed with water (200 mL) poured onto a silica gel column which was eluted with ethyl acetate

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

Procedure: 5-(4-Hydroxythiapyran-4-yl)-3-(2-pyrrolidinylethyl)-1H-indole: (56%) from 5-bromo-3-(2-pyrrolidinylethyl)-1H-indole (Example 3b); mp 66-78° C.; HRMS-FAB+ for C19H27N2OS: calculated MH+ :331.18442; found MH+ :331.18568.

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

Procedure: 5-(4-Hydroxythiapyran-4-yl)-3-(2-pyrrolidinylethyl)-1H-indole: (56%) from 5-bromo-3-(2-pyrrolidinylethyl)-1H-indole (Example 3b); mp 66-78° C.; HRMS-FAB+ for C19H27N2OS: calculated MH+ :331.18442; found MH+ :331.18568.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 5-bromo-3-(2-pyrrolidinylethyl)-1H-indole (Example 3b, 303 mg, 1.03 mmol) in ether (12.5 mL) was added to KH (42.9 mg, 1.07 mmol) at 0° C. After stirring at 0° C. for 20 minutes, the reaction mixture was cooled to -78° C. and a solution of tert-butyllithium in pentane (1.7 M, 0.22 mL, 2.1 mmol) was added dropwise. The reaction mixture was stirred at -78° C. for 30 minutes prior to the addition of cyclohexanone (0.22 mL, 2.1 mmol). The reaction was quenched by the addition of pH 7 buffer and the product was extracted into ethyl acetate, washed with water and brine, and dried over sodium sulfate. After removal of the solvent in vacuo, flash chromatography (silica, 5-10% 2M methanolic ammonia in dichloromethane) yielded 5-(1-hydroxycyclohex-1-yl)-3-(2-pyrrolidinylethyl)-1H-indole (116.4 mg, 36%); HRMS-FAB+ for C20H28N2O: calculated MH+ :313.22800; found MH+ :313.23151. the reaction mixture was cooled to -78° C. The reaction mixture was stirred at -78° C. for 30 minutes The reaction was quenched by the addition of pH 7 buffer the product was extracted into ethyl acetate washed with water and brine dried over sodium sulfate After removal of the solvent in vacuo, flash chromatography (silica, 5-10% 2M methanolic ammonia in dichloromethane)

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

Procedure: To a solution of 5-bromo-3-(2-pyrrolidinylethyl)-1H-indole (Example 2, 9.10 g, 31 mmol) in tetrahydrofuran (100 mL) cooled to 0° C., were added sodium hydride (12.4 g, 310 mmol) and p-toluenesulfonyl chloride (6.10 g, 32 mmol). The resulting mixture was stirred at room temperature for 3 h, poured into water (200 mL) and extracted into ethyl acetate (200 mL). The organic phase was washed with water (200 mL) and then poured onto a silica gel column which was eluted with ethyl acetate followed by methanol. The title compound was obtained as a yellow syrup (11.7 g, 90%). extracted into ethyl acetate (200 mL) The organic phase was washed with water (200 mL) poured onto a silica gel column which was eluted with ethyl acetate

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

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: 5-Bromo-1-(t-butyldimethylsilyl)-3-(2-pyrrolidin lethyl)indole: (1.02 g, 73%) as a brown oil from 5-bromo-3-(2-pyrrolidinylethyl)-1H-indole (Example 3b, 1.00 g, 3.4 mmol), sodium hexamethyldisilazide (82 mL, 6.82 mmol) and t-butyidimethylsilyl chloride (6.82 mL. 6.82 mmol). 13C NMR (CDCl3): 140.1, 132.9, 129.4, 124.1, 121.5, 116.3, 115.2, 112.7, 6.9, 54.3, 26.3, 25.1, 23.5, 19.5, −3.98.