cyclopropylmethylthiourea

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

実験手順: To 1-cyclopropylmethyl-2-thiourea (0.60 g, 4.6 mmol) in ethanol (10 mL) was added sodium methoxide (0.26 g, 4.8 mmol) and, after 5 minutes, ethyl cyanoacetate (0.50 mL, 4.6 mmol). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid. The solid was collected by filtration and washed with 2M aqueous acetic acid (10 mL), stirred with ethanol (10 mL) followed by evaporation and drying under reduced pressure, giving the title compound (0.51 g, 56%). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid The solid was collected by filtration washed with 2M aqueous acetic acid (10 mL) followed by evaporation drying under reduced pressure

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

実験手順: To 1-cyclopropylmethyl-2-thiourea (0.60 g, 4.6 mmol) in ethanol (10 mL) was added sodium methoxide (0.26 g, 4.8 mmol) and, after 5 minutes, ethyl cyanoacetate (0.50 mL, 4.6 mmol). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid. The solid was collected by filtration and washed with 2M aqueous acetic acid (10 mL), stirred with ethanol (10 mL) followed by evaporation and drying under reduced pressure, giving the title compound (0.51 g, 56%). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid The solid was collected by filtration washed with 2M aqueous acetic acid (10 mL) followed by evaporation drying under reduced pressure

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

実験手順: To 1-cyclopropylmethyl-2-thiourea (0.60 g, 4.6 mmol) in ethanol (10 mL) was added sodium methoxide (0.26 g, 4.8 mmol) and, after 5 minutes, ethyl cyanoacetate (0.50 mL, 4.6 mmol). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid. The solid was collected by filtration and washed with 2M aqueous acetic acid (10 mL), stirred with ethanol (10 mL) followed by evaporation and drying under reduced pressure, giving the title compound (0.51 g, 56%). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid The solid was collected by filtration washed with 2M aqueous acetic acid (10 mL) followed by evaporation drying under reduced pressure

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

実験手順: To 1-cyclopropylmethyl-2-thiourea (0.60 g, 4.6 mmol) in ethanol (10 mL) was added sodium methoxide (0.26 g, 4.8 mmol) and, after 5 minutes, ethyl cyanoacetate (0.50 mL, 4.6 mmol). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid. The solid was collected by filtration and washed with 2M aqueous acetic acid (10 mL), stirred with ethanol (10 mL) followed by evaporation and drying under reduced pressure, giving the title compound (0.51 g, 56%). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid The solid was collected by filtration washed with 2M aqueous acetic acid (10 mL) followed by evaporation drying under reduced pressure

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

実験手順: To 1-cyclopropylmethyl-2-thiourea (0.60 g, 4.6 mmol) in ethanol (10 mL) was added sodium methoxide (0.26 g, 4.8 mmol) and, after 5 minutes, ethyl cyanoacetate (0.50 mL, 4.6 mmol). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid. The solid was collected by filtration and washed with 2M aqueous acetic acid (10 mL), stirred with ethanol (10 mL) followed by evaporation and drying under reduced pressure, giving the title compound (0.51 g, 56%). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid The solid was collected by filtration washed with 2M aqueous acetic acid (10 mL) followed by evaporation drying under reduced pressure

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

実験手順: Slurry crude 2-bromo-1-(6-bromo-pyridin-3-yl)-ethanone (11.5 g, ca. 48%), N-cyclopropylmethyl thiourea (2.2 g, 16.9 mmol) and sodium bicarbonate (1.7 g, 20 mmol) in ethanol (100 mL) at room temperature. Stir the mixture at reflux for 1 h under a nitrogen atmosphere. Turn off heat and stir the mixture for an additional 16 h at room temperature. Filter the slurry, then wash the solids with ethanol (50 mL), water (2×50 mL) and hexane (excess). Dry the solid in a vacuum oven for 20 h at 50° C. to obtain the title compound as a tan solid (3.2 g, 61% yield over 2 steps). MS (ES+) m/z: 312 (M+2)+. at room temperature at reflux for 1 h under a nitrogen atmosphere heat stir the mixture for an additional 16 h at room temperature Filter the slurry wash the solids with ethanol (50 mL), water (2×50 mL) and hexane (excess) Dry the solid in a vacuum oven for 20 h at 50° C.

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

実験手順: Slurry 4-bromophenacyl bromide (11.2 g, 50 mmol) in absolute ethanol (50 mL). Add N-cyclopropylmethyl-thiourea (6.5 g, 50 mmol) and sodium bicarbonate (4.2 g, 50 mmol), heat to reflux for 2 h, then stir at room temperature overnight. Concentrate to ¼ volume and partition between water/EtOAc (4:1, 500 mL). Extract the aqueous layer with EtOAc (2×75 mL). Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo to obtain the title compound (14.0 g, 91%) as an off-white solid that was used without further purification. MS (ES+) m/z: 310 (M+H)+. to reflux for 2 h Concentrate partition between water/EtOAc (4:1, 500 mL) Extract the aqueous layer with EtOAc (2×75 mL) Dry the combined organic extracts over Na2SO4 filter concentrate in vacuo

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

実験手順: Slurry crude 6-(2-bromo-acetyl)-nicotinonitrile (5.2 g), cyclopropylmethyl-thiourea (2.7 g, 20.8 mmol) and sodium bicarbonate (1.95 g, 23.1 mmol) in ethanol (135 mL) at room temperature. Stir the mixture at reflux for 1 h under a nitrogen atmosphere. Cool the mixture to room temperature and concentrate in vacuo to a solid. Recrystallize from ethanol (20 mL) and water (100 mL) at 5° C. to obtain the desired intermediate as a tan solid (4.8 g, 81%). MS (ES+) m/z: 257 (M+H)+. at room temperature at reflux for 1 h under a nitrogen atmosphere concentrate in vacuo to a solid Recrystallize from ethanol (20 mL) and water (100 mL) at 5° C.

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

実験手順: Slurry crude 2-bromo-5-(2-bromo-acetyl)-pyridine (11.5 g, ca. 48%), cyclopropylmethyl-thiourea (2.2 g, 16.9 mmol) and sodium bicarbonate (1.7 g, 20 mmol) in ethanol (100 mL) at room temperature. Stir the mixture at reflux for 1 h under a nitrogen atmosphere. Turn off heat and stir the mixture for 16 h at room temperature. Filter the slurry, then wash the solids with ethanol (50 mL), water (2×50 mL) and hexane (excess). Dry the solid in a vacuum oven for 20 h at 50° C. to obtain the desired intermediate as a tan solid (3.2 g, 61% over 2 steps). MS (ES+) m/z: 312 (M+2)+. at room temperature at reflux for 1 h under a nitrogen atmosphere heat stir the mixture for 16 h at room temperature Filter the slurry wash the solids with ethanol (50 mL), water (2×50 mL) and hexane (excess) Dry the solid in a vacuum oven for 20 h at 50° C.

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

実験手順: To 1-cyclopropylmethyl-2-thiourea (0.60 g, 4.6 mmol) in ethanol (10 mL) was added sodium methoxide (0.26 g, 4.8 mmol) and, after 5 minutes, ethyl cyanoacetate (0.50 mL, 4.6 mmol). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid. The solid was collected by filtration and washed with 2M aqueous acetic acid (10 mL), stirred with ethanol (10 mL) followed by evaporation and drying under reduced pressure, giving the title compound (0.51 g, 56%). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid The solid was collected by filtration washed with 2M aqueous acetic acid (10 mL) followed by evaporation drying under reduced pressure