triethyl(triethylsilyloxy)silane

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

Procedure: A solution of 205 (15 mmol) in dimethylformamide (30 mL) is cooled to 0° C. and treated with imidazole (30 mmol) and triethylsilyl chloride (20 mmol). The resultant solution is warmed to room temperature. After 12 h, the reaction mixture is poured into 300 mL of water and extracted with ether (3×40 mL). The ethereal extracts are washed with water (2×25 mL) and saturated aqueous brine (25 mL), dried over magnesium sulfate and concentrated in vacuo. The residue is purified by flash chromatography to afford 206. extracted with ether (3×40 mL) The ethereal extracts are washed with water (2×25 mL) and saturated aqueous brine (25 mL) dried over magnesium sulfate concentrated in vacuo The residue is purified by flash chromatography

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

Procedure: To the resulting solution of mesylate (4) is added 4-mercaptopyridine (129 mg; 1.4 equivalents) and acetonitrile (2 ml) and stirred under ice cooling for 1 hour. The reaction mixture is poured into ice-water and adjusted at pH 6.0. The organic layer is separated, washed with aqueous sodium hydrogen carbonate and water, dried, and concentrated in vacuum to give pyridyl sulfide (7) as foamy residue. The organic layer is separated washed with aqueous sodium hydrogen carbonate and water dried concentrated in vacuum

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

Procedure: This solution of chloride (4) is mixed with 4-mercaptopyridine (2.45 g; 1.3 equivalents) and sodium carbonate (1.8 g; 1 equivalents) and concentrated in vacuum. The residue is dissolved in toluene, filtered to remove solid, and extracted with toluene. This is extracted with 2N-hydrochloric acid, mixed with sodium hydrogen carbonate, reextracted with toluene, and worked up as usual to give 4-pyridylsulfide (7) (7.87 g). Yield: 71%. IR (CHCl3)ν: 3100-2900, 1735, 1707, 1610, 1430 cm-1. concentrated in vacuum The residue is dissolved in toluene filtered to remove solid extracted with toluene This is extracted with 2N-hydrochloric acid mixed with sodium hydrogen carbonate

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

Procedure: This solution of resulting mesylate (4) is mixed with 4-mercaptopyridine (803 mg; 1.25 equivalents) and acetonitrile (22 ml), warmed to room temperature, and stirred for 2 hours to give a solution of pyridylsulfide (7).

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

Procedure: Cyclosporin A (3.606 g, 3 mmol) was dissolved in dry pyridine (8 mL) and then DMAP (122 mg, 1 mmol) was added. The reaction mixture was cooled to 0° C. and then triethylsilyl trifluoromethanesulfonate (3.6 mmol) added dropwise. The mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was then poured slowly into water with stirring. The precipitated triethylsilyl ether was filtered off and washed with water. The collected cake was dissolved in a minimum volume of methanol and added to a 5% citric acid solution and stirred for 30 minutes. The precipitated product was collected by filtration and washed with water until the pH of the filtrate reached that of the water. The solid triethylsilyl ether was dried at 50° C. under vacuum to give a colorless solid. Triisopropylsilyl and tert-butyldimethylsilyl protecting groups were also introduced by following an analogous procedure. to warm to room temperature with stirring The precipitated triethylsilyl ether was filtered off washed with water The collected cake was dissolved in a minimum volume of methanol added to a 5% citric acid solution stirred for 30 minutes The precipitated product was collected by filtration washed with water until the pH of the filtrate The solid triethylsilyl ether was dried at 50° C. under vacuum to give a colorless solid Triisopropylsilyl and tert-butyldimethylsilyl protecting groups were also introduced

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

Procedure: Cyclosporin A (3.606 g, 3 mmol) was dissolved in dry pyridine (8 mL) and then DMAP (122 mg, 1 mmol) was added. The reaction mixture was cooled to 0° C. and then triethylsilyl trifluoromethanesulfonate (3.6 mmol) added dropwise. The mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was then poured slowly into water with stirring. The precipitated triethylsilyl ether was filtered off and washed with water. The collected cake was dissolved in a minimum volume of methanol and added to a 5% citric acid solution and stirred for 30 minutes. The precipitated product was collected by filtration and washed with water until the pH of the filtrate reached that of the water. The solid triethylsilyl ether was dried at 50° C. under vacuum to give a colorless solid. Triisopropylsilyl and tert-butyldimethylsilyl protecting groups were also introduced by following an analogous procedure. to warm to room temperature with stirring The precipitated triethylsilyl ether was filtered off washed with water The collected cake was dissolved in a minimum volume of methanol added to a 5% citric acid solution stirred for 30 minutes The precipitated product was collected by filtration washed with water until the pH of the filtrate The solid triethylsilyl ether was dried at 50° C. under vacuum to give a colorless solid Triisopropylsilyl and tert-butyldimethylsilyl protecting groups were also introduced

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

Procedure: Cyclosporin A (3.606 g, 3 mmol) was dissolved in dry pyridine (8 mL) and then DMAP (122 mg, 1 mmol) was added. The reaction mixture was cooled to 0° C. and then triethylsilyl trifluoromethanesulfonate (3.6 mmol) added dropwise. The mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was then poured slowly into water with stirring. The precipitated triethylsilyl ether was filtered off and washed with water. The collected cake was dissolved in a minimum volume of methanol and added to a 5% citric acid solution and stirred for 30 minutes. The precipitated product was collected by filtration and washed with water until the pH of the filtrate reached that of the water. The solid triethylsilyl ether was dried at 50° C. under vacuum to give a colorless solid. Triisopropylsilyl and tert-butyldimethylsilyl protecting groups were also introduced by following an analogous procedure. to warm to room temperature with stirring The precipitated triethylsilyl ether was filtered off washed with water The collected cake was dissolved in a minimum volume of methanol added to a 5% citric acid solution stirred for 30 minutes The precipitated product was collected by filtration washed with water until the pH of the filtrate The solid triethylsilyl ether was dried at 50° C. under vacuum to give a colorless solid Triisopropylsilyl and tert-butyldimethylsilyl protecting groups were also introduced

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

Procedure: A solution of 205 (15 mmol) in dimethylformamide (30 mL) is cooled to 0° C. and treated with imidazole (30 mmol) and triethylsilyl chloride (20 mmol). The resultant solution is warmed to room temperature. After 12 h, the reaction mixture is poured into 300 mL of water and extracted with ether (3×40 mL). The ethereal extracts are washed with water (2×25 mL) and saturated aqueous brine (25 mL), dried over magnesium sulfate and concentrated in vacuo. The residue is purified by flash chromatography to afford 206. extracted with ether (3×40 mL) The ethereal extracts are washed with water (2×25 mL) and saturated aqueous brine (25 mL) dried over magnesium sulfate concentrated in vacuo The residue is purified by flash chromatography

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

Procedure: A solution of 205 (15 mmol) in dimethylformamide (30 mL) is cooled to 0° C. and treated with imidazole (30 mmol) and triethylsilyl chloride (20 mmol). The resultant solution is warmed to room temperature. After 12 h, the reaction mixture is poured into 300 mL of water and extracted with ether (3×40 mL). The ethereal extracts are washed with water (2×25 mL) and saturated aqueous brine (25 mL), dried over magnesium sulfate and concentrated in vacuo. The residue is purified by flash chromatography to afford 206. extracted with ether (3×40 mL) The ethereal extracts are washed with water (2×25 mL) and saturated aqueous brine (25 mL) dried over magnesium sulfate concentrated in vacuo The residue is purified by flash chromatography

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

Procedure: Cyclosporin A (3.606 g, 3 mmol) was dissolved in dry pyridine (8 mL) and then DMAP (122 mg, 1 mmol) was added. The reaction mixture was cooled to 0° C. and then triethylsilyl trifluoromethanesulfonate (3.6 mmol) added dropwise. The mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was then poured slowly into water with stirring. The precipitated triethylsilyl ether was filtered off and washed with water. The collected cake was dissolved in a minimum volume of methanol and added to a 5% citric acid solution and stirred for 30 minutes. The precipitated product was collected by filtration and washed with water until the pH of the filtrate reached that of the water. The solid triethylsilyl ether was dried at 50° C. under vacuum to give a colorless solid. Triisopropylsilyl and tert-butyldimethylsilyl protecting groups were also introduced by following an analogous procedure. to warm to room temperature with stirring The precipitated triethylsilyl ether was filtered off washed with water The collected cake was dissolved in a minimum volume of methanol added to a 5% citric acid solution stirred for 30 minutes The precipitated product was collected by filtration washed with water until the pH of the filtrate The solid triethylsilyl ether was dried at 50° C. under vacuum to give a colorless solid Triisopropylsilyl and tert-butyldimethylsilyl protecting groups were also introduced

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

Procedure: A solution of 205 (15 mmol) in dimethylformamide (30 mL) is cooled to 0° C. and treated with imidazole (30 mmol) and triethylsilyl chloride (20 mmol). The resultant solution is warmed to room temperature. After 12 h, the reaction mixture is poured into 300 mL of water and extracted with ether (3×40 mL). The ethereal extracts are washed with water (2×25 mL) and saturated aqueous brine (25 mL), dried over magnesium sulfate and concentrated in vacuo. The residue is purified by flash chromatography to afford 206. extracted with ether (3×40 mL) The ethereal extracts are washed with water (2×25 mL) and saturated aqueous brine (25 mL) dried over magnesium sulfate concentrated in vacuo The residue is purified by flash chromatography

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

Procedure: To the resulting solution of mesylate (4) is added 4-mercaptopyridine (129 mg; 1.4 equivalents) and acetonitrile (2 ml) and stirred under ice cooling for 1 hour. The reaction mixture is poured into ice-water and adjusted at pH 6.0. The organic layer is separated, washed with aqueous sodium hydrogen carbonate and water, dried, and concentrated in vacuum to give pyridyl sulfide (7) as foamy residue. The organic layer is separated washed with aqueous sodium hydrogen carbonate and water dried concentrated in vacuum