2-pyrrolidin-1-ylethanethiol

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a solution of 0.28 g of 1-(2-mercaptoethyl)pyrrolidine in 20 ml of dimethylformamide, 0.086 g of sodium hydride (60% dispersion in mineral oil) were added under nitrogen atmosphere, and the mixture stirred at room temperature for half an hr; a DMF solution of 1.0 g of 3β-(2-tosyloxyethoxy)-17β-(3-furyl)-5β-androstan-14β-ol, prepared as described in Ex. 7, was added and the mixture was stirred for another 4 hrs; the reaction mixture was quenched with water and extracted with methylene chloride. The organic layer was washed with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The crude product was purified by flash-cromatography (SiO2) using methylene chloride/methanol 95/5 as eluant and 0.90 g of the title compound (I-ai) as a white amorphous solid. 7, was added the mixture was stirred for another 4 hrs the reaction mixture was quenched with water extracted with methylene chloride The organic layer was washed with water dried over anhydrous sodium sulfate evaporated to dryness under reduced pressure The crude product was purified by flash-cromatography (SiO2)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium bicarbonate ((1.232 kg, 14.7 mol) is added slowly in portions to a mixture of 5-bromo-thiazol-2-ylamine hydrobromide (1.53 Kg, 5.87 mol) in 7.5 L of isopropanol. 2-Pyrrolidin-1-yl-ethanethiol (1.060 Kg, 8.07 mol) is then added over 15 min, and the resulting mixture is stirred at 60° C. for 96 h. The temperature is increased to 70° C. for 1 h, and then the mixture is cooled to room temperature. Most of the isopropanol is removed under vacuum, and the residue is taken up in 4 L of an isopropanol/chloroform solution (1:9). Saturated aqueous sodium bicarbonate (4 L) is added, and the resulting mixture is stirred for 30 minutes. The layers are separated and the aqueous phase is extracted with three 4 L portions of an isopropanol/chloroform solution (1:9). The organic layers are combined, dried over sodium sulfate, filtered, and concentrated under vacuum. The resulting residue is triturated with 3 L of diethylether, and filtered off to give a first portion of the title compound as a pale-yellow solid (410 g). The filtrate is concentrated to an orange solid, which is triturated with 2 L of diethylether, and isolated as a beige solid by filtration. This solid is then dissolved in 2 L of methanol, and the solution is heated at 45° C. for 30 min. Upon cooling to room temperature, a solid is formed. This material is isolated by filtration, triturated with diethyl ether as above, and dried under vacuum to afford an additional 310 g of the title compound. MS (m/e): 230 [M+H] The temperature is increased to 70° C. for 1 h the mixture is cooled to room temperature Most of the isopropanol is removed under vacuum Saturated aqueous sodium bicarbonate (4 L) is added the resulting mixture is stirred for 30 minutes The layers are separated the aqueous phase is extracted with three 4 L portions of an isopropanol/chloroform solution (1:9) dried over sodium sulfate filtered concentrated under vacuum The resulting residue is triturated with 3 L of diethylether filtered off

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

実験手順: To a solution of 0.28 g of 1-(2-mercaptoethyl)pyrrolidine in 20 ml of dimethylformamide, 0.086 g of sodium hydride (60% dispersion in mineral oil) were added under nitrogen atmosphere, and the mixture stirred at room temperature for half an hr; a DMF solution of 1.0 g of 3β-(2-tosyloxyethoxy)-17β-(3-furyl)-5β-androstan-14β-ol, prepared as described in Ex. 7, was added and the mixture was stirred for another 4 hrs; the reaction mixture was quenched with water and extracted with methylene chloride. The organic layer was washed with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The crude product was purified by flash-cromatography (SiO2) using methylene chloride/methanol 95/5 as eluant and 0.90 g of the title compound (I-ai) as a white amorphous solid. 7, was added the mixture was stirred for another 4 hrs the reaction mixture was quenched with water extracted with methylene chloride The organic layer was washed with water dried over anhydrous sodium sulfate evaporated to dryness under reduced pressure The crude product was purified by flash-cromatography (SiO2)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a solution of 0.28 g of 1-(2-mercaptoethyl)pyrrolidine in 20 ml of dimethylformamide, 0.086 g of sodium hydride (60% dispersion in mineral oil) were added under nitrogen atmosphere, and the mixture stirred at room temperature for half an hr; a DMF solution of 1.0 g of 3β-(2-tosyloxyethoxy)-17β-(3-furyl)-5β-androstan-14β-ol, prepared as described in Ex. 7, was added and the mixture was stirred for another 4 hrs; the reaction mixture was quenched with water and extracted with methylene chloride. The organic layer was washed with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The crude product was purified by flash-cromatography (SiO2) using methylene chloride/methanol 95/5 as eluant and 0.90 g of the title compound (I-ai) as a white amorphous solid. 7, was added the mixture was stirred for another 4 hrs the reaction mixture was quenched with water extracted with methylene chloride The organic layer was washed with water dried over anhydrous sodium sulfate evaporated to dryness under reduced pressure The crude product was purified by flash-cromatography (SiO2)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium bicarbonate ((1.232 kg, 14.7 mol) is added slowly in portions to a mixture of 5-bromo-thiazol-2-ylamine hydrobromide (1.53 Kg, 5.87 mol) in 7.5 L of isopropanol. 2-Pyrrolidin-1-yl-ethanethiol (1.060 Kg, 8.07 mol) is then added over 15 min, and the resulting mixture is stirred at 60° C. for 96 h. The temperature is increased to 70° C. for 1 h, and then the mixture is cooled to room temperature. Most of the isopropanol is removed under vacuum, and the residue is taken up in 4 L of an isopropanol/chloroform solution (1:9). Saturated aqueous sodium bicarbonate (4 L) is added, and the resulting mixture is stirred for 30 minutes. The layers are separated and the aqueous phase is extracted with three 4 L portions of an isopropanol/chloroform solution (1:9). The organic layers are combined, dried over sodium sulfate, filtered, and concentrated under vacuum. The resulting residue is triturated with 3 L of diethylether, and filtered off to give a first portion of the title compound as a pale-yellow solid (410 g). The filtrate is concentrated to an orange solid, which is triturated with 2 L of diethylether, and isolated as a beige solid by filtration. This solid is then dissolved in 2 L of methanol, and the solution is heated at 45° C. for 30 min. Upon cooling to room temperature, a solid is formed. This material is isolated by filtration, triturated with diethyl ether as above, and dried under vacuum to afford an additional 310 g of the title compound. MS (m/e): 230 [M+H] The temperature is increased to 70° C. for 1 h the mixture is cooled to room temperature Most of the isopropanol is removed under vacuum Saturated aqueous sodium bicarbonate (4 L) is added the resulting mixture is stirred for 30 minutes The layers are separated the aqueous phase is extracted with three 4 L portions of an isopropanol/chloroform solution (1:9) dried over sodium sulfate filtered concentrated under vacuum The resulting residue is triturated with 3 L of diethylether filtered off

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

実験手順: To a solution of 0.28 g of 1-(2-mercaptoethyl)pyrrolidine in 20 ml of dimethylformamide, 0.086 g of sodium hydride (60% dispersion in mineral oil) were added under nitrogen atmosphere, and the mixture stirred at room temperature for half an hr; a DMF solution of 1.0 g of 3β-(2-tosyloxyethoxy)-17β-(3-furyl)-5β-androstan-14β-ol, prepared as described in Ex. 7, was added and the mixture was stirred for another 4 hrs; the reaction mixture was quenched with water and extracted with methylene chloride. The organic layer was washed with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The crude product was purified by flash-cromatography (SiO2) using methylene chloride/methanol 95/5 as eluant and 0.90 g of the title compound (I-ai) as a white amorphous solid. 7, was added the mixture was stirred for another 4 hrs the reaction mixture was quenched with water extracted with methylene chloride The organic layer was washed with water dried over anhydrous sodium sulfate evaporated to dryness under reduced pressure The crude product was purified by flash-cromatography (SiO2)