ethyl 2-amino-2-phenylbutanoate

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

実験手順: 2.30 g of 2-amino-5-methyl-1,3,4-thiadiazole were dissolved at room temperature in 40 ml of dry tetrahydrofuran in a nitrogen atmosphere and with exclusion of moisture. 3.24 g of 1,1'-carbonyldiimidazole were then added. The mixture was stirred for 30 minutes at 50° C. 4.15 g of 2-amino-2-phenylbutyric acid ethyl ester (product from Example 3, stage 1) in 10 ml of dry tetrahydrofuran were added dropwise to the resultant suspension and stirred for 20 hours at 50° C. Once the solvent had been removed by distillation, the residue was recrystallised from ethanol. 3.94 g of 5-ethyl-3-(5-methyl[l.3.4]thiadiazol-2-yl)-5-phenyl-2,4-imidazolidinedione (58% of th.) were obtained in the form of white crystals (mp 223-225° C.). stirred for 20 hours at 50° C Once the solvent had been removed by distillation the residue was recrystallised from ethanol

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

実験手順: A solution of ethyl 2-amino-2-phenylbutanoate (0.162 g, 0.782 mmol) in 1:3 v/v water/ethanol (4 mL) was reacted with sodium borohydride (0.151 g, 3.908 mmol) at reflux for four hours. The reaction was concentrated and partition between water (5 mL), ethyl ether (10 mL) and 1N aqueous sodium hydroxide (0.39 mL). Solid sodium chloride was added to saturate the aqueous and separate the phases. The aqueous phase was separated and re-extracted with ethyl ether (2×20 mL). The combined ethereal extracts were washed with brine (25 mL), dried over potassium carbonate, filtered, and concentrated by rotary evaporation to afford the title compound as an oil (0.116 g, 0.702 mmol, 90%). 1H NMR (300 MHz, DMSO-D6) δ ppm 0.59 (t, J=7.54 Hz, 3 H) 1.49-1.80 (m, 4 H) 3.44 (d, J=5.15 Hz, 2 H) 4.63 (t, J=5.52 Hz, 1 H) 6.89-7.76 (m, 5 H). MS (DCI) m/z 166 (M+H)+. at reflux for four hours The reaction was concentrated partition between water (5 mL), ethyl ether (10 mL) and 1N aqueous sodium hydroxide (0.39 mL) Solid sodium chloride was added to saturate the aqueous and separate the phases The aqueous phase was separated re-extracted with ethyl ether (2×20 mL) The combined ethereal extracts were washed with brine (25 mL) dried over potassium carbonate filtered concentrated by rotary evaporation

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

実験手順: A solution of ethyl 2-amino-2-phenylbutanoate (0.162 g, 0.782 mmol) in 1:3 v/v water/ethanol (4 mL) was reacted with sodium borohydride (0.151 g, 3.908 mmol) at reflux for four hours. The reaction was concentrated and partition between water (5 mL), ethyl ether (10 mL) and 1N aqueous sodium hydroxide (0.39 mL). Solid sodium chloride was added to saturate the aqueous and separate the phases. The aqueous phase was separated and re-extracted with ethyl ether (2×20 mL). The combined ethereal extracts were washed with brine (25 mL), dried over potassium carbonate, filtered, and concentrated by rotary evaporation to afford the title compound as an oil (0.116 g, 0.702 mmol, 90%). 1H NMR (300 MHz, DMSO-D6) δ ppm 0.59 (t, J=7.54 Hz, 3 H) 1.49-1.80 (m, 4 H) 3.44 (d, J=5.15 Hz, 2 H) 4.63 (t, J=5.52 Hz, 1 H) 6.89-7.76 (m, 5 H). MS (DCI) m/z 166 (M+H)+. at reflux for four hours The reaction was concentrated partition between water (5 mL), ethyl ether (10 mL) and 1N aqueous sodium hydroxide (0.39 mL) Solid sodium chloride was added to saturate the aqueous and separate the phases The aqueous phase was separated re-extracted with ethyl ether (2×20 mL) The combined ethereal extracts were washed with brine (25 mL) dried over potassium carbonate filtered concentrated by rotary evaporation

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

実験手順: 12.72 mL of formic acid then 25.38 mL of acetic anhydride were added dropwise, under stirring, to 2.49 g (12.03 mmol) of amine 6. After 15 h at room temperature, solvents were removed under reduced pressure to give 3.09 g of 7 as a green viscous oil (100% yield). solvents were removed under reduced pressure

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

実験手順: The crude product 5 was dissolved in 22 mL of anhydrous THF and 2.64 mL of triethyl amine were added. After stirring for 30 minutes, the mixture was filtered through celite and the solid washed with 100 mL of anhydrous diethyl ether. Concentration of the solvents using a rotary evaporator afforded 2.49 g of 6 as a blue oil (77% yield). the mixture was filtered through celite the solid washed with 100 mL of anhydrous diethyl ether a rotary evaporator

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

実験手順: 2.30 g of 2-amino-5-methyl-1,3,4-thiadiazole were dissolved at room temperature in 40 ml of dry tetrahydrofuran in a nitrogen atmosphere and with exclusion of moisture. 3.24 g of 1,1'-carbonyldiimidazole were then added. The mixture was stirred for 30 minutes at 50° C. 4.15 g of 2-amino-2-phenylbutyric acid ethyl ester (product from Example 3, stage 1) in 10 ml of dry tetrahydrofuran were added dropwise to the resultant suspension and stirred for 20 hours at 50° C. Once the solvent had been removed by distillation, the residue was recrystallised from ethanol. 3.94 g of 5-ethyl-3-(5-methyl[l.3.4]thiadiazol-2-yl)-5-phenyl-2,4-imidazolidinedione (58% of th.) were obtained in the form of white crystals (mp 223-225° C.). stirred for 20 hours at 50° C Once the solvent had been removed by distillation the residue was recrystallised from ethanol

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

実験手順: A solution of ethyl 2-amino-2-phenylbutanoate (0.162 g, 0.782 mmol) in 1:3 v/v water/ethanol (4 mL) was reacted with sodium borohydride (0.151 g, 3.908 mmol) at reflux for four hours. The reaction was concentrated and partition between water (5 mL), ethyl ether (10 mL) and 1N aqueous sodium hydroxide (0.39 mL). Solid sodium chloride was added to saturate the aqueous and separate the phases. The aqueous phase was separated and re-extracted with ethyl ether (2×20 mL). The combined ethereal extracts were washed with brine (25 mL), dried over potassium carbonate, filtered, and concentrated by rotary evaporation to afford the title compound as an oil (0.116 g, 0.702 mmol, 90%). 1H NMR (300 MHz, DMSO-D6) δ ppm 0.59 (t, J=7.54 Hz, 3 H) 1.49-1.80 (m, 4 H) 3.44 (d, J=5.15 Hz, 2 H) 4.63 (t, J=5.52 Hz, 1 H) 6.89-7.76 (m, 5 H). MS (DCI) m/z 166 (M+H)+. at reflux for four hours The reaction was concentrated partition between water (5 mL), ethyl ether (10 mL) and 1N aqueous sodium hydroxide (0.39 mL) Solid sodium chloride was added to saturate the aqueous and separate the phases The aqueous phase was separated re-extracted with ethyl ether (2×20 mL) The combined ethereal extracts were washed with brine (25 mL) dried over potassium carbonate filtered concentrated by rotary evaporation