3-(2-bromophenyl)propan-1-amine

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 20-mL sealed tube, was placed methyl 3-chloro-2-phenylquinoxaline-6-carboxylate (180 mg, 0.60 mmol, 1.00 equiv), toluene/DMSO (5/1 mL), 3-(2-bromophenyl)propan-1-amine (385 mg, 1.80 mmol, 2.99 equiv), and potassium carbonate (414 mg, 3.00 mmol, 4.98 equiv). The resulting solution was stirred overnight at 100° C. The mixture was concentrated under vacuum. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:50). This resulted in 240 mg (80%) of methyl 3-(3-(2-bromophenyl)propylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid. Into a 20-mL sealed tube The mixture was concentrated under vacuum The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:50) This resulted in 240 mg (80%) of methyl 3-(3-(2-bromophenyl)propylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid

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

Procedure: Into a 250-mL 3-necked round-bottom flask, was placed a solution of 3-(2-bromophenyl)propanenitrile (2.1 g, 10.00 mmol, 1.00 equiv) in tetrahydrofuran (20 mL). This was followed by the addition of borane (1 mol/L in THF, 50 mL, 5.00 equiv) dropwise with stiffing at 0° C. The resulting solution was stirred for overnight at room temperature. The reaction was then quenched by the addition of 50 mL of water at 0° C. and extracted with 3×50 mL of ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was dissolved in 30 mL of 6N aqueous hydrogen chloride. The aqueous solution was extracted with 30 mL of ethyl acetate and the aqueous layers were combined. The pH value of the aqueous solution was adjusted to 10 with 10% aqueous sodium hydroxide. The resulting solution was extracted with 3×50 mL of ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate, concentrated under vacuum. This resulted in 1.3 g (58%) of 3-(2-bromophenyl)propan-1-amine as colorless oil. Into a 250-mL 3-necked round-bottom flask, was placed with stiffing at 0° C The reaction was then quenched by the addition of 50 mL of water at 0° C. extracted with 3×50 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum The residue was dissolved in 30 mL of 6N aqueous hydrogen chloride The aqueous solution was extracted with 30 mL of ethyl acetate The resulting solution was extracted with 3×50 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 1.3 g (58%) of 3-(2-bromophenyl)propan-1-amine as colorless oil

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

Procedure: Into a 250-mL 3-necked round-bottom flask, was placed a solution of 3-(2-bromophenyl)propanenitrile (2.1 g, 10.00 mmol, 1.00 equiv) in tetrahydrofuran (20 mL). This was followed by the addition of borane (1 mol/L in THF, 50 mL, 5.00 equiv) dropwise with stiffing at 0° C. The resulting solution was stirred for overnight at room temperature. The reaction was then quenched by the addition of 50 mL of water at 0° C. and extracted with 3×50 mL of ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was dissolved in 30 mL of 6N aqueous hydrogen chloride. The aqueous solution was extracted with 30 mL of ethyl acetate and the aqueous layers were combined. The pH value of the aqueous solution was adjusted to 10 with 10% aqueous sodium hydroxide. The resulting solution was extracted with 3×50 mL of ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate, concentrated under vacuum. This resulted in 1.3 g (58%) of 3-(2-bromophenyl)propan-1-amine as colorless oil. Into a 250-mL 3-necked round-bottom flask, was placed with stiffing at 0° C The reaction was then quenched by the addition of 50 mL of water at 0° C. extracted with 3×50 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum The residue was dissolved in 30 mL of 6N aqueous hydrogen chloride The aqueous solution was extracted with 30 mL of ethyl acetate The resulting solution was extracted with 3×50 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 1.3 g (58%) of 3-(2-bromophenyl)propan-1-amine as colorless oil

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

Procedure: A mixture of 3-(2-bromophenyl)-propylamine (6.9 g, 30 mmol), 2-bromomethyl-benzoic acid methyl ester (6.42 g, 30 mmol), and K2CO3 (6.91 g, 50 mmol) in toluene (100 mL) was heated at reflux with stirring for 2 h. Workup and silica gel column chromatography using a gradient of hexanes to 50% ethyl acetate in hexanes afforded 2-[3-(2-bromophenyl)-propyl]-2,3-dihydroisoindol-1-one (5.7 g, 58%). GC/MS gave: m/z (rel.int.) 331 (M+, 3), 329 (M+, 3), 250 (42), 147 (82), 146 (100) 119 (27), and 91 (47). 1H NMR (300 MHz, CDCl3): δ 2.00 (dt, 2H), 2.80 (t, 2H), 3.74 (t, 2H), 4.40 (s, 2H), 7.04 (dt, 1H), 7.19-7.27 (m, 3H), 7.43-7.53 (m, 3H), 7.76 (dd, 1H). 13C NMR (300 MHz, CDCl3): δ 28.7, 33.7, 42.1, 50.0, 122.8, 123.8, 124.4, 127.7, 127.9, 128.1, 130.6, 131.3, 132.9, 133.1, 140.8, 141.3, 168.7. was heated at reflux

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

Procedure: A mixture of 3-(2-bromophenyl)-propylamine (6.9 g, 30 mmol), 2-bromomethyl-benzoic acid methyl ester (6.42 g, 30 mmol), and K2CO3 (6.91 g, 50 mmol) in toluene (100 mL) was heated at reflux with stirring for 2 h. Workup and silica gel column chromatography using a gradient of hexanes to 50% ethyl acetate in hexanes afforded 2-[3-(2-bromophenyl)-propyl]-2,3-dihydroisoindol-1-one (5.7 g, 58%). GC/MS gave: m/z (rel.int.) 331 (M+, 3), 329 (M+, 3), 250 (42), 147 (82), 146 (100) 119 (27), and 91 (47). 1H NMR (300 MHz, CDCl3): δ 2.00 (dt, 2H), 2.80 (t, 2H), 3.74 (t, 2H), 4.40 (s, 2H), 7.04 (dt, 1H), 7.19-7.27 (m, 3H), 7.43-7.53 (m, 3H), 7.76 (dd, 1H). 13C NMR (300 MHz, CDCl3): δ 28.7, 33.7, 42.1, 50.0, 122.8, 123.8, 124.4, 127.7, 127.9, 128.1, 130.6, 131.3, 132.9, 133.1, 140.8, 141.3, 168.7. was heated at reflux

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 20-mL sealed tube, was placed methyl 3-chloro-2-phenylquinoxaline-6-carboxylate (180 mg, 0.60 mmol, 1.00 equiv), toluene/DMSO (5/1 mL), 3-(2-bromophenyl)propan-1-amine (385 mg, 1.80 mmol, 2.99 equiv), and potassium carbonate (414 mg, 3.00 mmol, 4.98 equiv). The resulting solution was stirred overnight at 100° C. The mixture was concentrated under vacuum. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:50). This resulted in 240 mg (80%) of methyl 3-(3-(2-bromophenyl)propylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid. Into a 20-mL sealed tube The mixture was concentrated under vacuum The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:50) This resulted in 240 mg (80%) of methyl 3-(3-(2-bromophenyl)propylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 250-mL 3-necked round-bottom flask, was placed a solution of 3-(2-bromophenyl)propanenitrile (2.1 g, 10.00 mmol, 1.00 equiv) in tetrahydrofuran (20 mL). This was followed by the addition of borane (1 mol/L in THF, 50 mL, 5.00 equiv) dropwise with stirring at 0° C. The resulting solution was stirred for overnight at room temperature. The reaction was then quenched by the addition of 50 mL of water at 0° C. and extracted with 3×50 mL of ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was dissolved in 30 mL of 6N aqueous hydrogen chloride. The aqueous solution was extracted with 30 mL of ethyl acetate and the aqueous layers were combined. The pH value of the aqueous solution was adjusted to 10 with 10% aqueous sodium hydroxide. The resulting solution was extracted with 3×50 mL of ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate, concentrated under vacuum. This resulted in 1.3 g (58%) of 3-(2-bromophenyl)propan-1-amine as colorless oil. Into a 250-mL 3-necked round-bottom flask, was placed The resulting solution was stirred for overnight at room temperature The reaction was then quenched by the addition of 50 mL of water at 0° C. extracted with 3×50 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum The residue was dissolved in 30 mL of 6N aqueous hydrogen chloride The aqueous solution was extracted with 30 mL of ethyl acetate The resulting solution was extracted with 3×50 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 1.3 g (58%) of 3-(2-bromophenyl)propan-1-amine as colorless oil

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 20-mL sealed tube, was placed methyl 3-chloro-2-phenylquinoxaline-6-carboxylate (180 mg, 0.60 mmol, 1.00 equiv), toluene/DMSO (5/1 mL), 3-(2-bromophenyl)propan-1-amine (385 mg, 1.80 mmol, 2.99 equiv), and potassium carbonate (414 mg, 3.00 mmol, 4.98 equiv). The resulting solution was stirred overnight at 100° C. The mixture was concentrated under vacuum. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:50). This resulted in 240 mg (80%) of methyl 3-(3-(2-bromophenyl)propylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid. Into a 20-mL sealed tube The mixture was concentrated under vacuum The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:50) This resulted in 240 mg (80%) of methyl 3-(3-(2-bromophenyl)propylamino)-2-phenylquinoxaline-6-carboxylate as a yellow solid

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

Procedure: Into a 250-mL 3-necked round-bottom flask, was placed a solution of 3-(2-bromophenyl)propanenitrile (2.1 g, 10.00 mmol, 1.00 equiv) in tetrahydrofuran (20 mL). This was followed by the addition of borane (1 mol/L in THF, 50 mL, 5.00 equiv) dropwise with stiffing at 0° C. The resulting solution was stirred for overnight at room temperature. The reaction was then quenched by the addition of 50 mL of water at 0° C. and extracted with 3×50 mL of ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was dissolved in 30 mL of 6N aqueous hydrogen chloride. The aqueous solution was extracted with 30 mL of ethyl acetate and the aqueous layers were combined. The pH value of the aqueous solution was adjusted to 10 with 10% aqueous sodium hydroxide. The resulting solution was extracted with 3×50 mL of ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate, concentrated under vacuum. This resulted in 1.3 g (58%) of 3-(2-bromophenyl)propan-1-amine as colorless oil. Into a 250-mL 3-necked round-bottom flask, was placed with stiffing at 0° C The reaction was then quenched by the addition of 50 mL of water at 0° C. extracted with 3×50 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum The residue was dissolved in 30 mL of 6N aqueous hydrogen chloride The aqueous solution was extracted with 30 mL of ethyl acetate The resulting solution was extracted with 3×50 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 1.3 g (58%) of 3-(2-bromophenyl)propan-1-amine as colorless oil