3-chloropropanenitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 500 mL round bottom flask equipped with an overhead stirrer and under an inert atmosphere was added 25 g of 1,3-dichloroacetone (0.197 mol) and 75 g of acetone. The reaction mixture was cooled to 10° C. and 23.2 g 2-imino-4-thiobiuret (0.197 mol) was added. The reaction mixture was stirred for one hour at 10 C. The reaction mixture was then heated to 40° C. and 15 g of thiourea (0.197 mol) was added, followed by the addition of 100 g of water. The mixture was heated to and held at 52° C. for one hour. Acetone was then removed by vacuum distillation. To the reaction mixture was added 100 g of water, 17 g of 3-chloropropionitrile (0.190 mol) and 40 g of isopropyl alcohol. The reaction mixture was cooled below 10° C. and 25 g of an aqueous solution of sodium hydroxide (80 g water) was added dropwise maintaining the reaction temperature below 10° C. The reaction mixture was for 2 hours, filtered and washed to produce 28 g of N-[4-(cyanoethylthiomethyl)-2-thiazolyl]guanidine product. Into a 500 mL round bottom flask equipped with an overhead stirrer and under an inert atmosphere The reaction mixture was then heated to 40° C. The mixture was heated to and held at 52° C. for one hour Acetone was then removed by vacuum distillation The reaction mixture was cooled below 10° C. maintaining the reaction temperature below 10° C The reaction mixture was for 2 hours filtered washed

反応条件: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sulfamide (9.6 g, 0.1 mole) was added to a solution of conc. sulfuric acid (98%, 9.8 g, 0.1 mole) in 3-chloropropionitrile (51.3 g, 0.6 mole). The suspension was heated at 55-60° C., for 18 hours. At the end of the heating period, the mixture was cooled to room temperature, diluted with methylene chloride (150 ml), and filtered. The solid, thus obtained, was suspended in acetone (50 ml), and the suspension filtered and the product dried. At the end of the heating period, the mixture was cooled to room temperature filtered The solid, thus obtained the suspension filtered the product dried

反応条件: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sulfamide (9.6 g, 0.1 mole) was added to a solution of 2,4,6-trichlorobenzenesulfonic acid (52.2 g, 0.2 mole) in 3-chloropropionitrile (51.3 g, 0.6 mole). The suspension was heated at 55-60° C., for 18 hours. At the end of the heating period, the mixture was cooled to room temperature, diluted with methylene chloride (150 ml), and filtered. The solid, thus obtained, was suspended in acetone (50 ml) and the suspension filtered and the product dried. At the end of the heating period, the mixture was cooled to room temperature filtered The solid, thus obtained the suspension filtered the product dried

反応条件: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sulfamide (9.6 g, 0.1 mole) was added to a suspension of benzenesulfonic acid (31.6 g, 0.2 mole) in 3-chloropropionitrile (51.3 g, 0.6 mole). The suspension was heated at 55-60° C., for 18 hours. At the end of the heating period, the mixture was cooled to room temperature, diluted with methylene chloride (150 ml), and filtered. The solid, thus obtained, was suspended in acetone (50 ml), and the suspension filtered and the product dried. At the end of the heating period, the mixture was cooled to room temperature filtered The solid, thus obtained the suspension filtered the product dried

反応条件: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sulfamide (9.6 g, 0.1 mole) was added to a suspension of p-toluenesulfonic acid monohydrate (38.0 g, 0.2 mole) in 3-chloropropionitrile (51.3 g, 0.6 mole). The suspension was heated at 55-60° C., for 18 hours. At the end of the heating period, the mixture was cooled to room temperature, diluted with methylene chloride (150 ml), and filtered. The solid, thus obtained, was suspended in acetone (50 ml) and the suspension filtered and the product dried. At the end of the heating period, the mixture was cooled to room temperature filtered The solid, thus obtained the suspension filtered the product dried

反応条件: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sulfamide (9.6 g, 0.1 mole) was added to a solution of methanesulfonic acid anhydrous (48.0 g, 0.5 mole) in 3-chloropropionitrile (51.3 g, 0.6 mole). The suspension was heated at 55-60° C., for 18 hours. At the end of the reacting period, the mixture was diluted with methylene chloride (150 ml), and filtered. The solid, thus obtained, was suspended in acetone (50 ml), and the suspension filtered and the product dried, to yield 13.3 g of product. filtered The solid, thus obtained the suspension filtered the product dried

反応条件: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sulfamide (9.6 g, 0.1 mole) was added to a solution of methanesulfonic acid anhydrous (38.4 g, 0.4 mole) in 3-chloropropionitrile (51.3 g, 0.6 mole). The suspension was heated at 55-60° C., for 18 hours. At the end of the reacting period, the mixture was diluted with methylene chloride (150 ml) and filtered. The solid, thus obtained, was suspended in acetone (50 ml), and the suspension filtered and the product dried, to yield 16.35 g of product. filtered The solid, thus obtained the suspension filtered the product dried

反応条件: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sulfamide (9.6 g, 0.1 mole) was added to a solution of methanesulfonic acid anhydrous (19.2 g, 0.2 mole) in 3-chloropropionitrile (51.3 g, 0.6 mole). The suspension was heated at 55-60° C., for 18 hours. At the end of the heating period, the mixture was cooled to room temperature, diluted with methylene chloride (150 ml), and filtered. The solid, thus obtained, was suspended in acetone (50 ml), and the suspension filtered and the product dried, to yield about 19 g of product. At the end of the heating period, the mixture was cooled to room temperature filtered The solid, thus obtained the suspension filtered the product dried

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

実験手順: Using 2.35 ml of 3-chloropropionitrile, 2.0 g of imidazole and 1.3 g of sodium hydride (60%), 3.2 g of 1-(2-cyanoethyl)imidazole was obtained by the same manner as the procedure of Reference Example 2.

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Pyrazole-4-boronic acid pinacol ester (1 g, 1 equiv, 5.15 mmol) was dissolved in dimethylformamide (15 mL) followed by the addition of Cs2CO3 (0.86 g, 1.5 equiv, 7.73 mmol) and 3-chloropropionitrile (1.1 equiv, 5.67 mmol, 0.44 mL). The mixture was heated at 90° C. overnight. The reaction was diluted with ethyl acetate and washed with water (3×) and brine (3×). The organic phases was concentrated in vacuo onto silica gel and purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10) to return the title compound (0.11 g, 9%). 1H NMR (500 MHz, DMSO): δ 1.26 (12H, s), 3.07 (2H, t), 4.40 (2H, t), 7.65 (1H, s), 8.04 (1H, s). MS m/z 248 (M+H+)+. washed with water (3×) and brine (3×) The organic phases was concentrated in vacuo onto silica gel purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Pyrazole-4-boronic acid pinacol ester (1 g, 1 equiv, 5.15 mmol) was dissolved in dimethylformamide (15 mL) followed by the addition of Cs2CO3 (0.86 g, 1.5 equiv, 7.73 mmol) and 3-chloropropionitrile (1.1 equiv, 5.67 mmol, 0.44 mL). The mixture was heated at 90° C. overnight. The reaction was diluted with ethyl acetate and washed with water (3×) and brine (3×). The organic phases was concentrated in vacuo onto silica gel and purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10) to return the title compound (0.11 g, 9%). 1H NMR (500 MHz, DMSO): δ 1.26 (12H, s), 3.07 (2H, t), 4.40 (2H, t), 7.65 (1H, s), 8.04 (1H, s). MS m/z 248 (M+H+)+. washed with water (3×) and brine (3×) The organic phases was concentrated in vacuo onto silica gel purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10)