N-cyclopropyl-2-sulfanylacetamide

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

Procedure: To a solution of N-cyclopropyl-2-mercapto-acetamide (0.452 g, 3.45 mmol) in MeOH (5 ml) is added sodium methoxide solution (25% wt. in MeOH)(0.589 ml, 2.58 mmol). The resulting solution is stirred at room temperature for 30 minutes, then treated with a 1:1 mixture of 2,5-dichloro-6-(2-methoxy-ethoxy)-4-methyl-nicotinonitrile and 5,6-dichloro-2-(2-methoxy-ethoxy)-4-methyl-nicotinonitrile (0.450 g, 1.72 mmol). The reaction vessel is sealed, heated at 100° C. for 2.5 hours, and cooled to room temperature. The reaction mixture is poured over water (60 ml), then extracted with EtOAc (2×40 ml). The combined organic layers are washed with brine (50 ml), dried (anhydrous magnesium sulfate), filtered, and concentrated to give a yellow-brown solid. Flash chromatography (1.5:1 hexane:EtOAc) affords the title compound as a cream colored solid (53 mg, 10%). Mass (m/z): 356.1 (M++1). The reaction vessel is sealed heated at 100° C. for 2.5 hours cooled to room temperature extracted with EtOAc (2×40 ml) The combined organic layers are washed with brine (50 ml) dried (anhydrous magnesium sulfate) filtered concentrated to give a yellow-brown solid

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

Procedure: To a solution of N-cyclopropyl-2-mercapto-acetamide (0.498 g, 3.80 mmol) in MeOH (5 ml) is added sodium methoxide solution (25% wt. in MeOH)(0.652 ml, 2.85 mmol). The resulting solution is stirred at room temperature for 30 minutes, then treated with a 1:1 mixture of 2,5-dichloro-6-isopropoxy-4-methyl-nicotinonitrile and 5,6-dichloro-2-isopropoxy-4-methyl-nicotinonitrile (0.400 g, 1.63 mmol). The reaction vessel is sealed, heated at 100° C. for 2.5 hours, and cooled to room temperature. The reaction mixture is poured over water (60 ml), then extracted with EtOAc (2×40 ml). The combined organic layers are washed with brine (50 ml), dried (anhydrous magnesium sulfate), filtered, and concentrated to give a yellow-brown solid. Flash chromatography (1.5:1 hexane:EtOAc) affords the title compound as a tan solid (20 mg). Mass (m/z): 340.1 (M++1). The reaction vessel is sealed heated at 100° C. for 2.5 hours cooled to room temperature extracted with EtOAc (2×40 ml) The combined organic layers are washed with brine (50 ml) dried (anhydrous magnesium sulfate) filtered concentrated to give a yellow-brown solid

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

Procedure: To a solution of N-cyclopropyl-2-mercapto-acetamide (0.498 g, 3.80 mmol) in MeOH (5 ml) is added sodium methoxide solution (25% wt. in MeOH)(0.652 ml, 2.85 mmol). The resulting solution is stirred at room temperature for 30 minutes, then treated with a 1:1 mixture of 2,5-dichloro-6-isopropoxy-4-methyl-nicotinonitrile and 5,6-dichloro-2-isopropoxy-4-methyl-nicotinonitrile (0.400 g, 1.63 mmol). The reaction vessel is sealed, heated at 100° C. for 2.5 hours, and cooled to room temperature. The reaction mixture is poured over water (60 ml), then extracted with EtOAc (2×40 ml). The combined organic layers are washed with brine (50 ml), dried (anhydrous magnesium sulfate), filtered, and concentrated to give a yellow-brown solid. Flash chromatography (1.5:1 hexane:EtOAc) affords the title compound as a tan solid (20 mg). Mass (m/z): 340.1 (M++1). The reaction vessel is sealed heated at 100° C. for 2.5 hours cooled to room temperature extracted with EtOAc (2×40 ml) The combined organic layers are washed with brine (50 ml) dried (anhydrous magnesium sulfate) filtered concentrated to give a yellow-brown solid

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

Procedure: To a solution of N-cyclopropyl-2-mercapto-acetamide (6.65 g, 50.68 mmol) in MeOH (100 ml), is added sodium methoxide solution (25% wt. in MeOH)(11.59 ml, 50.68 mmol). The resulting solution is stirred at room temperature for 10 minutes, and then treated with 2,5-dichloro-6-methoxy-4-methyl-nicotinonitrile (10.0 g, 46.07 mmol). The reaction vessel is sealed and heated at 100° C. for 2 hours. The reaction mixture is cooled to room temperature and poured over 500 ml of cold water. A thick white precipitate is formed. The mixture is stirred at 0° C. for 10 minutes, then the solid is collected by filtration. The fluffy white solid (title compound) is placed in the vacuum oven at 60° C. to dry overnight (7.74 g, 54%). Mass (m/z): 312.0 (M++1). The reaction vessel is sealed heated at 100° C. for 2 hours The reaction mixture is cooled to room temperature A thick white precipitate is formed The mixture is stirred at 0° C. for 10 minutes the solid is collected by filtration is placed in the vacuum oven at 60° C. to dry overnight (7.74 g, 54%)

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

Procedure: To a solution of N-cyclopropyl-2-mercapto-acetamide (6.65 g, 50.68 mmol) in MeOH (100 ml), is added sodium methoxide solution (25% wt. in MeOH)(11.59 ml, 50.68 mmol). The resulting solution is stirred at room temperature for 10 minutes, and then treated with 2,5-dichloro-6-methoxy-4-methyl-nicotinonitrile (10.0 g, 46.07 mmol). The reaction vessel is sealed and heated at 100° C. for 2 hours. The reaction mixture is cooled to room temperature and poured over 500 ml of cold water. A thick white precipitate is formed. The mixture is stirred at 0° C. for 10 minutes, then the solid is collected by filtration. The fluffy white solid (title compound) is placed in the vacuum oven at 60° C. to dry overnight (7.74 g, 54%). Mass (m/z): 312.0 (M++1). The reaction vessel is sealed heated at 100° C. for 2 hours The reaction mixture is cooled to room temperature A thick white precipitate is formed The mixture is stirred at 0° C. for 10 minutes the solid is collected by filtration is placed in the vacuum oven at 60° C. to dry overnight (7.74 g, 54%)

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

Procedure: To a solution of N-cyclopropyl-2-mercapto-acetamide (0.452 g, 3.45 mmol) in MeOH (5 ml) is added sodium methoxide solution (25% wt. in MeOH)(0.589 ml, 2.58 mmol). The resulting solution is stirred at room temperature for 30 minutes, then treated with a 1:1 mixture of 2,5-dichloro-6-(2-methoxy-ethoxy)-4-methyl-nicotinonitrile and 5,6-dichloro-2-(2-methoxy-ethoxy)-4-methyl-nicotinonitrile (0.450 g, 1.72 mmol). The reaction vessel is sealed, heated at 100° C. for 2.5 hours, and cooled to room temperature. The reaction mixture is poured over water (60 ml), then extracted with EtOAc (2×40 ml). The combined organic layers are washed with brine (50 ml), dried (anhydrous magnesium sulfate), filtered, and concentrated to give a yellow-brown solid. Flash chromatography (1.5:1 hexane:EtOAc) affords the title compound as a cream colored solid (53 mg, 10%). Mass (m/z): 356.1 (M++1). The reaction vessel is sealed heated at 100° C. for 2.5 hours cooled to room temperature extracted with EtOAc (2×40 ml) The combined organic layers are washed with brine (50 ml) dried (anhydrous magnesium sulfate) filtered concentrated to give a yellow-brown solid

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

Procedure: To a solution of N-cyclopropyl-2-mercapto-acetamide (0.498 g, 3.80 mmol) in MeOH (5 ml) is added sodium methoxide solution (25% wt. in MeOH)(0.652 ml, 2.85 mmol). The resulting solution is stirred at room temperature for 30 minutes, then treated with a 1:1 mixture of 2,5-dichloro-6-isopropoxy-4-methyl-nicotinonitrile and 5,6-dichloro-2-isopropoxy-4-methyl-nicotinonitrile (0.400 g, 1.63 mmol). The reaction vessel is sealed, heated at 100° C. for 2.5 hours, and cooled to room temperature. The reaction mixture is poured over water (60 ml), then extracted with EtOAc (2×40 ml). The combined organic layers are washed with brine (50 ml), dried (anhydrous magnesium sulfate), filtered, and concentrated to give a yellow-brown solid. Flash chromatography (1.5:1 hexane:EtOAc) affords the title compound as a tan solid (20 mg). Mass (m/z): 340.1 (M++1). The reaction vessel is sealed heated at 100° C. for 2.5 hours cooled to room temperature extracted with EtOAc (2×40 ml) The combined organic layers are washed with brine (50 ml) dried (anhydrous magnesium sulfate) filtered concentrated to give a yellow-brown solid

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

Procedure: To a solution of N-cyclopropyl-2-mercapto-acetamide (6.65 g, 50.68 mmol) in MeOH (100 ml), is added sodium methoxide solution (25% wt. in MeOH)(11.59 ml, 50.68 mmol). The resulting solution is stirred at room temperature for 10 minutes, and then treated with 2,5-dichloro-6-methoxy-4-methyl-nicotinonitrile (10.0 g, 46.07 mmol). The reaction vessel is sealed and heated at 100° C. for 2 hours. The reaction mixture is cooled to room temperature and poured over 500 ml of cold water. A thick white precipitate is formed. The mixture is stirred at 0° C. for 10 minutes, then the solid is collected by filtration. The fluffy white solid (title compound) is placed in the vacuum oven at 60° C. to dry overnight (7.74 g, 54%). Mass (m/z): 312.0 (M++1). The reaction vessel is sealed heated at 100° C. for 2 hours The reaction mixture is cooled to room temperature A thick white precipitate is formed The mixture is stirred at 0° C. for 10 minutes the solid is collected by filtration is placed in the vacuum oven at 60° C. to dry overnight (7.74 g, 54%)