2-(4-chlorophenyl)propan-2-amine

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

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

Procedure: Epichlorohydrin (8.05 ml) was added dropwise to a solution of 1-(4-chlorophenyl)-1-methylethylamine (17.38 g) in methanol (17.5 ml) at 0° C. with stirring. The solution was warmed to ambient temperature and stirred for 48 hours. Sodium hydroxide solution (50%) (17.5 ml) was added and the mixture stirred for 15 minutes. The product was extracted with ether to give an oil which was purified by flash column chromatography on silica using petroleum ether, b.p. 40-60° C./ethyl acetate/triethylamine (8:2:1) as the mobile phase with gradually increasing amounts of ethyl acetate to give N-[1-(4-chlorophenyl)-1-methylethyl]-2,3-epoxypropylamine as an oil. stirred for 48 hours the mixture stirred for 15 minutes The product was extracted with ether to give an oil which was purified by flash column chromatography on silica

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

Procedure: Epichlorohydrin (8.05 ml) was added dropwise to a solution of 1-(4-chlorophenyl)-1-methylethylamine (17.38 g) in methanol (17.5 ml) at 0° C. with stirring. The solution was warmed to ambient temperature and stirred for 48 hours. Sodium hydroxide solution (50%) (17.5 ml) was added and the mixture stirred for 15 minutes. The product was extracted with ether to give an oil which was purified by flash column chromatography on silica using petroleum ether, b.p. 40-60° C./ethyl acetate/triethylamine (8:2:1) as the mobile phase with gradually increasing amounts of ethyl acetate to give N-[1-(4-chlorophenyl)-1-methylethyl]-2,3-epoxypropylamine as an oil. stirred for 48 hours the mixture stirred for 15 minutes The product was extracted with ether to give an oil which was purified by flash column chromatography on silica

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

Procedure: 2-(4-chlorophenyl)propan-2-amine (21 mg, 0.123 mmol) was added to a stirring solution of HATU (59 mg, 0.154 mmol), DIEA (54 μL, 0.308 mmol), and 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (40 mg, 0.103 mmol) in DMF (1 mL) at rt. It was allowed to stir for 1 hour. The mixture was diluted with EtOAc and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and was purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/CH3CN gradient, and concentrated to give the titled compound (32 mg, 57%). 1H NMR (500 MHz, DMSO-d6) d ppm 8.64 (1 H, s), 8.47-8.55 (1 H, m), 8.14 (1 H, s), 7.99-8.04 (2 H, m), 7.92 (1 H, s), 7.74-7.89 (4 H, m), 7.57 (1 H, t, J=7.78 Hz), 7.37-7.45 (4 H, m), 7.34 (2 H, d, J=8.85 Hz), 2.87 (3 H, d, J=4.58 Hz), 1.69 (6 H, s). LC-MS retention time: 1.95 min; m/z (MH+): 541. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10 u C18 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode. Additional HPLC method: Solvent A=5% CH3CN/95% H2O/0.1% TFA, Solvent B=95% CH3CN/5% H2O/0.1% TFA, Start % B=10, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min. Column: Waters Sunfire C-18, 4.6×150 mm, 3.5 mm, Rt=15.18 min, purity=99%; Column: Waters Xbridge Phenyl column 4 6×150 mm, 3.5 mm, Rt=13.66 min, purity=99%. washed The organic phase was dried over Na2SO4 filtered concentrated was purified by preparative reverse phase HPLC on a C18 column concentrated

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

Procedure: N-(2-Fluoro-4-chloro-5-cyclopentyloxyphenyl)-3,4,5,6-tetrahydroisophthalimide (0.900 g, 2.74 mmol), 4-chlorocumylamine (0.600 g, 3.54 mmol), N-methylmorpholine (0.300 g, 2.97 mmol), and benzene (15 ml) as a solvent were placed into a round bottom flask (50 cc) and stirred overnight at room temperature. After completion of the reaction, the solvent was distilled off under reduced pressure, and the precipitated crystals were isolated by filtration. The crystals were washed with hexane and dried to obtain N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-N'-(4-chlorocumyl)-3,4,5,6-tetrahydrophthalamide as white crystals (0.404 g, 30.7% yield). After completion of the reaction the solvent was distilled off under reduced pressure the precipitated crystals were isolated by filtration The crystals were washed with hexane dried

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

Procedure: 2-(4-Chlorophenyl)propan-2-amine (21 mg, 0.123 mmol) was added to a stirring solution of HATU (59 mg, 0.154 mmol), DIEA (54 μL, 0.308 mmol), and 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (40 mg, 0.103 mmol) in DMF (1 mL) at rt. It was allowed to stir for 1 hour. The mixture was diluted with EtOAc and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and was purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/CH3CN gradient, and concentrated to give the titled compound (32 mg, 57%). 1H NMR (500 MHz, DMSO-d6) δ ppm 8.64 (1H, s), 8.47-8.55 (1H, m), 8.14 (1H, s), 7.99-8.04 (2H, m), 7.92 (1H, s), 7.74-7.89 (4H, m), 7.57 (1H, t, J=7.78 Hz), 7.37-7.45 (4H, m), 7.34 (2H, d, J=8.85 Hz), 2.87 (3H, d, J=4.58 Hz), 1.69 (6H, s). LC-MS retention time: 1.95 min; m/z (MH+): 541. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 10u C18 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. Additional HPLC method: Solvent A=5% CH3CN/95% H2O/0.1% TFA, Solvent B=95% CH3CN/5% H2O/0.1% TFA, Start % B=10, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min. Column: Waters Sunfire C-18, 4.6×150 mm, 3.5 mm, Rt=15.18 min, purity=99%; Column: Waters XBridge phenyl column 4.6×150 mm, 3.5 mm, Rt=13.66 min, purity=99%. washed The organic phase was dried over Na2SO4 filtered concentrated was purified by preparative reverse phase HPLC on a C18 column concentrated

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

Procedure: Epichlorohydrin (8.05 ml) was added dropwise to a solution of 1-(4-chlorophenyl)-1-methylethylamine (17.38 g) in methanol (17.5 ml) at 0° C. with stirring. The solution was warmed to ambient temperature and stirred for 48 hours. Sodium hydroxide solution (50%) (17.5 ml) was added and the mixture stirred for 15 minutes. The product was extracted with ether to give an oil which was purified by flash column chromatography on silica using petroleum ether, b.p. 40-60° C./ethyl acetate/triethylamine (8:2:1) as the mobile phase with gradually increasing amounts of ethyl acetate to give N-[1-(4-chlorophenyl)-1-methylethyl]-2,3-epoxypropylamine as an oil. stirred for 48 hours the mixture stirred for 15 minutes The product was extracted with ether to give an oil which was purified by flash column chromatography on silica

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

Procedure: Epichlorohydrin (8.05 ml) was added dropwise to a solution of 1-(4-chlorophenyl)-1-methylethylamine (17.38 g) in methanol (17.5 ml) at 0° C. with stirring. The solution was warmed to ambient temperature and stirred for 48 hours. Sodium hydroxide solution (50%) (17.5 ml) was added and the mixture stirred for 15 minutes. The product was extracted with ether to give an oil which was purified by flash column chromatography on silica using petroleum ether, b.p. 40-60° C./ethyl acetate/triethylamine (8:2:1) as the mobile phase with gradually increasing amounts of ethyl acetate to give N-[1-(4-chlorophenyl)-1-methylethyl]-2,3-epoxypropylamine as an oil. stirred for 48 hours the mixture stirred for 15 minutes The product was extracted with ether to give an oil which was purified by flash column chromatography on silica

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

Procedure: Epichlorohydrin (8.05 ml) was added dropwise to a solution of 1-(4-chlorophenyl)-1-methylethylamine (17.38 g) in methanol (17.5 ml) at 0° C. with stirring. The solution was warmed to ambient temperature and stirred for 48 hours. Sodium hydroxide solution (50%) (17.5 ml) was added and the mixture stirred for 15 minutes. The product was extracted with ether to give an oil which was purified by flash column chromatography on silica using petroleum ether, b.p. 40-60° C./ethyl acetate/triethylamine (8:2:1) as the mobile phase with gradually increasing amounts of ethyl acetate to give N-[1-(4-chlorophenyl)-1-methylethyl]-2,3-epoxypropylamine as an oil. stirred for 48 hours the mixture stirred for 15 minutes The product was extracted with ether to give an oil which was purified by flash column chromatography on silica

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

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

Procedure: Epichlorohydrin (8.05 ml) was added dropwise to a solution of 1-(4-chlorophenyl)-1-methylethylamine (17.38 g) in methanol (17.5 ml) at 0° C. with stirring. The solution was warmed to ambient temperature and stirred for 48 hours. Sodium hydroxide solution (50%) (17.5 ml) was added and the mixture stirred for 15 minutes. The product was extracted with ether to give an oil which was purified by flash column chromatography on silica using petroleum ether, b.p. 40-60° C./ethyl acetate/triethylamine (8:2:1) as the mobile phase with gradually increasing amounts of ethyl acetate to give N-[1-(4-chlorophenyl)-1-methylethyl]-2,3-epoxypropylamine as an oil. stirred for 48 hours the mixture stirred for 15 minutes The product was extracted with ether to give an oil which was purified by flash column chromatography on silica

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

Procedure: Epichlorohydrin (8.05 ml) was added dropwise to a solution of 1-(4-chlorophenyl)-1-methylethylamine (17.38 g) in methanol (17.5 ml) at 0° C. with stirring. The solution was warmed to ambient temperature and stirred for 48 hours. Sodium hydroxide solution (50%) (17.5 ml) was added and the mixture stirred for 15 minutes. The product was extracted with ether to give an oil which was purified by flash column chromatography on silica using petroleum ether, b.p. 40°-60° C./ethyl acetate/triethylamine (8:2:1) as the mobile phase with gradually increasing amounts of ethyl acetate to give N-[1-(4-chlorophenyl)-1-methylethyl]-2,3-epoxypropylamine as an oil. stirred for 48 hours the mixture stirred for 15 minutes The product was extracted with ether to give an oil which was purified by flash column chromatography on silica