1,1,3,3-tetramethylthiourea

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

実験手順: First the gold(I) starting compound, aurous bis(tetramethyl-thiourea) tetrafluoroborate, was made as follows. HAuCl4.3H2O (0.255 g) was dissolved in 5 mL water and added dropwise to tetramethylthiourea (0.327 g) which was partly dissolved in water. Dark orange and red precipitates formed initially, but after stirring at about 50° to 60° C. the precipitates dissolved and the solution became completely clear and colorless. 0.2 mL HBF4 solution (49% aqueous) was added. After cooling a few hours, white platelets of the product were filtered (84% yield). This intermediate gold(I) compound (0.228 g) was dissolved in 4 mL water by heating to about 60° C., and then added to a room temperature solution of 1,4,5-trimethyl-1,2,4-triazolium-3-thiolate (0.126 g). A white precipitate began to form, and was filtered after standing in the refrigerator a few hours. The product yield was 86%. The product could be recrystallized from hot water. Elemental analysis conformed to the formula for compound 1, and a single-crystal x-ray diffraction study confirmed the structure as a linear, two-coordinate complex with gold-sulfur bond lengths averaging 2.27 angstroms. Dark orange and red precipitates formed initially dissolved After cooling a few hours white platelets of the product were filtered (84% yield) This intermediate gold(I) compound (0.228 g) was dissolved in 4 mL water added to a room temperature solution of 1,4,5-trimethyl-1,2,4-triazolium-3-thiolate (0.126 g) to form was filtered after standing in the refrigerator a few hours

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

実験手順: To a solution of 44 mg (0.33 mmol) 1,1,3,3-tetramethyl-2-thiourea in 1.5 ml N,N-dimethylformamide were added 0.027 ml iodomethane at room temperature. After stirring for 50 min. 0.20 g (0.33 mmol) (S)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[4-(4-fluoro-2-methyl-phenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)-pyridin-3-yl]-N-methyl-isobutyramide and a suspension of 45 mg (0.90 mmol) sodium hydride (ca. 50% dispersion in mineral oil) in 0.5 ml n-hexane were added. After stirring at room temperature for 1 h the reaction mixture was diluted with water and extracted with three portions of tert-butyl methyl ether. The combined organic extracts were dried over sodium sulphate and concentrated. Flash column chromatography gave 90 mg (40%) of the title compound as an off-white solid. were added After stirring at room temperature for 1 h the reaction mixture extracted with three portions of tert-butyl methyl ether The combined organic extracts were dried over sodium sulphate concentrated

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

実験手順: To a solution of 44 mg (0.33 mmol) 1,1,3,3-tetramethyl-2-thiourea in 1.5 ml N,N-dimethylformamide were added 0.027 ml iodomethane at room temperature. After stirring for 50 min. 0.20 g (0.33 mmol) (S)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[4-(4-fluoro-2-methyl-phenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)-pyridin-3-yl]-N-methyl-isobutyramide and a suspension of 45 mg (0.90 mmol) sodium hydride (ca. 50% dispersion in mineral oil) in 0.5 ml n-hexane were added. After stirring at room temperature for 1 h the reaction mixture was diluted with water and extracted with three portions of tert-butyl methyl ether. The combined organic extracts were dried over sodium sulphate and concentrated. Flash column chromatography gave 90 mg (40%) of the title compound as an off-white solid. were added After stirring at room temperature for 1 h the reaction mixture extracted with three portions of tert-butyl methyl ether The combined organic extracts were dried over sodium sulphate concentrated

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: a solution of 14 g (0.11 mol) of tetramethylthiourea and 28 g (0.10 mol) of ethyl 6-iodocaproate in 220 ml of dry acetonitrile was heated under reflux for 2 h. In a further reaction vessel 23 g (0.16 mol) of 1,8-octanediol was dissolved in 650 ml of dry acetonitrile under argon, the solution was treated with 4.5 g (0.11 mol) of a 60 percent sodium hydride suspension in mineral oil and heated under reflux for 45 min. Both batches were left to cool to 50° C. and thereupon combined cautiously within 30 min. The combined reaction mixtures were heated to reflux for 14 h., subsequently saponified with 60 ml of 10 percent potassium hydroxide solution for 3 h. at room temp., concentrated on a rotary evaporator and then added to 1 l of water. The mixture was extracted twice with 500 ml of MTBE each time, and the organic extracts were washed three times with 50 ml of 2N sodium hydroxide solution each time. The aqueous phase was acidified with conc. phosphoric acid and extracted three times with 500 ml of MTBE each time. After drying the combined organic extracts over magnesium sulphate and removing the solvent on a rotary evaporator 22 g of crude 15-hydroxy-7-thiapentadecanoic acid as a yellowish wax-like solid was obtained. An analytical sample was obtained after flash chromotography (MTBE/n-pentane, 2:1, hRf =33) on silica gel. under reflux for 2 h heated under reflux for 45 min Both batches were left The combined reaction mixtures were heated to reflux for 14 h. concentrated on a rotary evaporator added to 1 l of water The mixture was extracted twice with 500 ml of MTBE each time the organic extracts were washed three times with 50 ml of 2N sodium hydroxide solution each time extracted three times with 500 ml of MTBE each time After drying the combined organic extracts over magnesium sulphate removing the solvent on a rotary evaporator 22 g of crude 15-hydroxy-7-thiapentadecanoic acid as a yellowish wax-like solid was obtained

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

実験手順: First the gold(I) starting compound, aurous bis(tetramethyl-thiourea) tetrafluoroborate, was made as follows. HAuCl4.3H2O (0.255 g) was dissolved in 5 mL water and added dropwise to tetramethylthiourea (0.327 g) which was partly dissolved in water. Dark orange and red precipitates formed initially, but after stirring at about 50° to 60° C. the precipitates dissolved and the solution became completely clear and colorless. 0.2 mL HBF4 solution (49% aqueous) was added. After cooling a few hours, white platelets of the product were filtered (84% yield). This intermediate gold(I) compound (0.228 g) was dissolved in 4 mL water by heating to about 60° C., and then added to a room temperature solution of 1,4,5-trimethyl-1,2,4-triazolium-3-thiolate (0.126 g). A white precipitate began to form, and was filtered after standing in the refrigerator a few hours. The product yield was 86%. The product could be recrystallized from hot water. Elemental analysis conformed to the formula for compound 1, and a single-crystal x-ray diffraction study confirmed the structure as a linear, two-coordinate complex with gold-sulfur bond lengths averaging 2.27 angstroms. Dark orange and red precipitates formed initially dissolved After cooling a few hours white platelets of the product were filtered (84% yield) This intermediate gold(I) compound (0.228 g) was dissolved in 4 mL water added to a room temperature solution of 1,4,5-trimethyl-1,2,4-triazolium-3-thiolate (0.126 g) to form was filtered after standing in the refrigerator a few hours

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

実験手順: To a solution of 44 mg (0.33 mmol) 1,1,3,3-tetramethyl-2-thiourea in 1.5 ml N,N-dimethylformamide were added 0.027 ml iodomethane at room temperature. After stirring for 50 min. 0.20 g (0.33 mmol) (S)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[4-(4-fluoro-2-methyl-phenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)-pyridin-3-yl]-N-methyl-isobutyramide and a suspension of 45 mg (0.90 mmol) sodium hydride (ca. 50% dispersion in mineral oil) in 0.5 ml n-hexane were added. After stirring at room temperature for 1 h the reaction mixture was diluted with water and extracted with three portions of tert-butyl methyl ether. The combined organic extracts were dried over sodium sulphate and concentrated. Flash column chromatography gave 90 mg (40%) of the title compound as an off-white solid. were added After stirring at room temperature for 1 h the reaction mixture extracted with three portions of tert-butyl methyl ether The combined organic extracts were dried over sodium sulphate concentrated

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

実験手順: First the gold(I) starting compound, aurous bis(tetramethylthiourea) tetrafluoroborate, was made as follows. HAuCl4.3H2O (0.255 g) was dissolved in 5 mL water and added dropwise to tetramethylthiourea (0.327 g) which was partly dissolved in water. Dark orange and red precipitates formed initially, but after stirring at about 50° to 60° C. the precipitates dissolved and the solution become completely clear and colorless. 0.2 mL HBF4 solution (49% aqueous) was added. After cooling a few hours, white platelets of the product were filtered (84% yield). This intermediate gold(I) compound (0.228 g) was dissolved in 4 mL water by heating to about 60° C., and then added to a room temperature solution of 1,4,5-trimethyl-1,2,4-triazolium-3-thiolate (0.126 g). A white precipitate began to form, and was filtered after standing in the refrigerator a few hours. The product yield was 86%. The product could be recrystallized from hot water. Elemental analysis conformed to the formula for compound 1, and a single-crystal x-ray diffraction study confirmed the structure as a linear, two-coordinate complex with gold-sulfur bond lengths averaging 2.27 angstroms. Dark orange and red precipitates formed initially dissolved After cooling a few hours white platelets of the product were filtered (84% yield) This intermediate gold(I) compound (0.228 g) was dissolved in 4 mL water added to a room temperature solution of 1,4,5-trimethyl-1,2,4-triazolium-3-thiolate (0.126 g) to form was filtered after standing in the refrigerator a few hours

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

実験手順: To a solution of 44 mg (0.33 mmol) 1,1,3,3-tetramethyl-2-thiourea in 1.5 ml N,N-dimethylformamide were added 0.027 ml iodomethane at room temperature. After stirring for 50 min. 0.20 g (0.33 mmol) (S)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[4-(4-fluoro-2-methyl-phenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)-pyridin-3-yl]-N-methyl-isobutyramide and a suspension of 45 mg (0.90 mmol) sodium hydride (ca. 50% dispersion in mineral oil) in 0.5 ml n-hexane were added. After stirring at room temperature for 1 h the reaction mixture was diluted with water and extracted with three portions of tert-butyl methyl ether. The combined organic extracts were dried over sodium sulphate and concentrated. Flash column chromatography gave 90 mg (40%) of the title compound as an off-white solid. were added After stirring at room temperature for 1 h the reaction mixture extracted with three portions of tert-butyl methyl ether The combined organic extracts were dried over sodium sulphate concentrated