3-(3-chloroanilino)propanenitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 2-(tert-butoxycarbonyl(methyl)amino)acetic acid (1.05 g, 0.0056 mol) in CH2Cl2 at 0° C. under argon atmosphere was added DMAP (0.021 g), 3-(3-chlorophenylamino)propanenitrile (1 g, 0.0056 mol) and DCC (1.27 g, 0.0061 mol). The reaction mixture was allowed to stir at room temperature for 24 h. The resulting suspension was filtered, the filtrate concentrated under reduced pressure and the crude residue was subjected to silica gel chromatography to give the tert-butyl 2-((3-chlorophenyl)(2-cyanoethyl)amino)-2-oxoethyl(methyl)carbamate (1.2 g, 80%). 1H NMR (CDCl3) δ 1.45 (s, 9H), 2.7 (m, 2H), 2.85 (m, 2H), 3.6-3.75 (m, 2H), 3.9 (m, 2H), 7.1-7.3 (m, 2H), 7.4 (m, 2H). The resulting suspension was filtered the filtrate concentrated under reduced pressure

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

Procedure: To a solution of 3-chlorobenzenamine (10 g, 0.079 mol) and acrylonitrile (5.0 g, 0.095 mol), Cu(OAc)2 (0.5 g, 5% by weight of 3-chlorobenzenamine), were heated under reflux, beginning at about 95° C. The reaction is heated at reflux for 3 h with the temperature rising to ˜130° C. Upon completion of the reaction, the acrylonitrile was stripped under reduced pressure. The residue was purified by column chromatography to afford the pure product 3-(3-chlorophenylamino)propanenitrile (8 g, yield 67%). under reflux beginning at about 95° C The reaction is heated at reflux for 3 h with the temperature rising to ˜130° C Upon completion of the reaction The residue was purified by column chromatography

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

Procedure: 3-(3-chlorophenylamino)propanenitrile (2 g, 0.011 mol) was dissolved in anhydrous THF (20 mL) and heated to reflux under nitrogen. A solution of BH3.MeS in THF was added drop wise and stirred at reflux overnight. The resulting solution was cooled to room temperature. Methanol was added drop wise to quench the reaction. After evaporation of the solution, the crude product was purified by column chromatography to afford the pure product N1-(3-chlorophenyl)propane-1,3-diamine (1.89 g, yield 95%) heated to reflux under nitrogen at reflux overnight to quench the reaction After evaporation of the solution the crude product was purified by column chromatography

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

Procedure: A solution of 3-chlorobenzenamine (10 g, 0.079 mol), Cu(OAc)2 (0.5 g, 5% by weight of m-chloroaniline), and acrylonitrile, was heated to reflux. Refluxing was continued for 3 h with the temperature rising to about 130° C. After the reaction was complete, acrylonitrile was stripped under reduced pressure and the residue purified by column chromatography to afford the pure product 3-(3-chlorophenylamino)propanenitrile (8 g, yield 67%). 1HNMR δ 2.6 (m, 2H), 3.5 (m, 2H), 4.1 (m, 1H), 6.45 (m, 1H), 6.55 (m, 1H), 7.1 (m, 1H). Refluxing rising to about 130° C the residue purified by column chromatography

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 2-(tert-butoxycarbonyl(methyl)amino)acetic acid (1.05 g, 0.0056 mol) in CH2Cl2 at 0° C. under argon atmosphere was added DMAP (0.021 g), 3-(3-chlorophenylamino)propanenitrile (1 g, 0.0056 mol) and DCC (1.27 g, 0.0061 mol). The reaction mixture was allowed to stir at room temperature for 24 h. The resulting suspension was filtered, the filtrate concentrated under reduced pressure and the crude residue was subjected to silica gel chromatography to give the tert-butyl 2-((3-chlorophenyl)(2-cyanoethyl)amino)-2-oxoethyl(methyl)carbamate (1.2 g, 80%). 1H NMR (CDCl3) δ 1.45 (s, 9H), 2.7 (m, 2H), 2.85 (m, 2H), 3.6-3.75 (m, 2H), 3.9 (m, 2H), 7.1-7.3 (m, 2H), 7.4 (m, 2H). The resulting suspension was filtered the filtrate concentrated under reduced pressure

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

Procedure: To a solution of 2-(tert-butoxycarbonyl(methyl)amino)acetic acid (1.05 g, 0.0056 mol) in CH2Cl2 at 0° C. under argon atmosphere was added DMAP (0.021 g), 3-(3-chlorophenylamino)propanenitrile (1 g, 0.0056 mol) and DCC (1.27 g, 0.0061 mol). The reaction mixture was allowed to stir at room temperature for 24 h. The resulting suspension was filtered, the filtrate concentrated under reduced pressure and the crude residue was subjected to silica gel chromatography to give the tert-butyl 2-((3-chlorophenyl)(2-cyanoethyl)amino)-2-oxoethyl(methyl)carbamate (1.2 g, 80%). 1H NMR (CDCl3) δ 1.45 (s, 9H), 2.7 (m, 2H), 2.85 (m, 2H), 3.6-3.75 (m, 2H), 3.9 (m, 2H), 7.1-7.3 (m, 2H), 7.4 (m, 2H). The resulting suspension was filtered the filtrate concentrated under reduced pressure

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

Procedure: To a solution of 3-chlorobenzenamine (10 g, 0.079 mol) and acrylonitrile (5.0 g, 0.095 mol), Cu(OAc)2 (0.5 g, 5% by weight of 3-chlorobenzenamine), were heated under reflux, beginning at about 95° C. The reaction is heated at reflux for 3 h with the temperature rising to ˜130° C. Upon completion of the reaction, the acrylonitrile was stripped under reduced pressure. The residue was purified by column chromatography to afford the pure product 3-(3-chlorophenylamino)propanenitrile (8 g, yield 67%). under reflux beginning at about 95° C The reaction is heated at reflux for 3 h with the temperature rising to ˜130° C Upon completion of the reaction The residue was purified by column chromatography

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

Procedure: To a solution of 3-chlorobenzenamine (10 g, 0.079 mol) and acrylonitrile (5.0 g, 0.095 mol), Cu(OAc)2 (0.5 g, 5% by weight of 3-chlorobenzenamine), were heated under reflux, beginning at about 95° C. The reaction is heated at reflux for 3 h with the temperature rising to ˜130° C. Upon completion of the reaction, the acrylonitrile was stripped under reduced pressure. The residue was purified by column chromatography to afford the pure product 3-(3-chlorophenylamino)propanenitrile (8 g, yield 67%). under reflux beginning at about 95° C The reaction is heated at reflux for 3 h with the temperature rising to ˜130° C Upon completion of the reaction The residue was purified by column chromatography

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

Procedure: 3-(3-chlorophenylamino)propanenitrile (2 g, 0.011 mol) was dissolved in anhydrous THF (20 mL) and heated to reflux under nitrogen. A solution of BH3.MeS in THF was added drop wise and stirred at reflux overnight. The resulting solution was cooled to room temperature. Methanol was added drop wise to quench the reaction. After evaporation of the solution, the crude product was purified by column chromatography to afford the pure product N1-(3-chlorophenyl)propane-1,3-diamine (1.89 g, yield 95%) heated to reflux under nitrogen at reflux overnight to quench the reaction After evaporation of the solution the crude product was purified by column chromatography