(1S)-1-(3-bromophenyl)ethanamine

Conditions: temp:195.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-1-(3-bromo-phenyl)-ethylamine (1.5 g, 7.5 mmol) and pyrazole (1.02 g, 15 mmol) in N-methylpyrrolidinone (10 mL) in a quartz tube were added potassium carbonate (2.1 g, 15 mmol), and copper (1) iodide (143 mg, 0.75 mmole), and the resulting mixture was heated at 195° C. for 5 h in a Mars 5 microwave oven (600 W). The reaction mixture was cooled down to room temperature and filtered. The crude product was purified by flash chromatography (10% MeOH/89% EtOAc/1% triethylamine) to provide the title compound (814 mg, 58% yield) as a brown oil. The reaction mixture was cooled down to room temperature filtered The crude product was purified by flash chromatography (10% MeOH/89% EtOAc/1% triethylamine)

Conditions: temp:195.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-1-(3-bromo-phenyl)-ethylamine (1.5 g, 7.5 mmol) and 1,2,4-triazole (1.04 g, 15 mmol) in N-methylpyrrolidinone (10 mL) in a quartz tube were added potassium carbonate (2.1 g, 15 mmol) and copper (1) iodide (143 mg, 0.75 mmol). The reaction mixture was heated at 195° C. for 5 h in a Mars 5 microwave oven (600 W), cooled down to room temperature and filtered. The crude product was purified by flash chromatography (10% MeOH/89% EtOAC/1% triethylamine) to provide the title compound (504 mg, 36% yield) as a brown oil. cooled down to room temperature filtered The crude product was purified by flash chromatography (10% MeOH/89% EtOAC/1% triethylamine)

Conditions: temp:195.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-1-(3-bromo-phenyl)-ethylamine (1.5 g, 7.5 mmol) and 1,2,4-triazole (1.04 g, 15 mmol) in N-methylpyrrolidinone (10 mL) in a quartz tube were added potassium carbonate (2.1 g, 15 mmol) and copper (1) iodide (143 mg, 0.75 mmol). The reaction mixture was heated at 195° C. for 5 h in a Mars 5 microwave oven (600 W), cooled down to room temperature and filtered. The crude product was purified by flash chromatography (10% MeOH/89% EtOAC/1% triethylamine) to provide the title compound (504 mg, 36% yield) as a brown oil. cooled down to room temperature filtered The crude product was purified by flash chromatography (10% MeOH/89% EtOAC/1% triethylamine)

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

Procedure: To a stirred ice-cooled solution of (S)-(−)-3-bromo-α-methylbenzylamine (832 mg, 4.16 mmol, from Chiragene) in 15.6 mL of THF was added 1.33 g (4.99 mmol, 1.20 eq.) of 2,4-dinitrobenzenesulfonyl chloride, followed by 1.08 mL (6.20 mmol, 1.49 eq.) of N,N-diisopropylethylamine. The ice bath was removed, and the mixture was stirred at room temperature for 19 h and then concentrated. The residue was taken up in EtOAc, washed with 2×H2O, dried over Na2SO4, filtered, and concentrated. The residue was sonicated in ca. 5 mL of EtOAc until a precipitate was formed. The mixture was diluted to ca. 25 mL with hexanes. Filtration afforded product as a tan solid (1.69 g, 94.4% yield). The ice bath was removed concentrated washed with 2×H2O dried over Na2SO4 filtered concentrated The residue was sonicated in ca. 5 mL of EtOAc until a precipitate was formed Filtration

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

Procedure: To a stirred ice-cooled solution of (S)-(−)-3-bromo-α-methylbenzylamine (832 mg, 4.16 mmol, from Chiragene) in 15.6 mL of THF was added 1.33 g (4.99 mmol, 1.20 eq.) of 2,4-dinitrobenzenesulfonyl chloride, followed by 1.08 mL (6.20 mmol, 1.49 eq.) of N,N-diisopropylethylamine. The ice bath was removed, and the mixture was stirred at room temperature for 19 h and then concentrated. The residue was taken up in EtOAc, washed with 2×H2O, dried over Na2SO4, filtered, and concentrated. The residue was sonicated in ca. 5 mL of EtOAc until a precipitate was formed. The mixture was diluted to ca. 25 mL with hexanes. Filtration afforded product as a tan solid (1.69 g, 94.4% yield). The ice bath was removed concentrated washed with 2×H2O dried over Na2SO4 filtered concentrated The residue was sonicated in ca. 5 mL of EtOAc until a precipitate was formed Filtration

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

Procedure: Commercially available (S)-1-(3-bromophenyl)ethanamine (1.0 g, 5 mmol) was dissolved in THF (20 mL). Pyridine (0.5 mL) and acetic anhydride (0.51 g, 5 mmol) were added and the reaction mixture allowed to stir at room temperature overnight. The solvent was removed under reduced pressure to provide A4a.1 (1.23 g) as a clear yellowish liquid. (M+H)+=242.15, 244.16. The solvent was removed under reduced pressure to provide A4a.1 (1.23 g) as a clear yellowish liquid

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 20 ml microwave vial was weighted 1-(pyridin-2-yl)propan-2-one ligand (90 mg, 0.665 mmol), phenol (407 mg, 4.32 mmol), CuBr (47.7 mg, 0.332 mmol) and Cs2CO3 (2166 mg, 6.65 mmol). To the mixture was added DMSO (5 ml) and (S)-1-(3-bromophenyl)ethanamine (0.5 ml, 3.32 mmol). The tube was flushed with N2, capped, and the black mixture heated in the oil bath at 90° C. for 18 hours. The heterogenous mixture was diluted with EtOAc and filtered through a glass-fritted funnel, eluting with EtOAc and another 5 mls of DMSO. The volatiles were then removed in vacuo and the crude brown liquid was filtered through 1 um PTFE filter and purified by reverse phase HPLC. The combined product fractions were desalted by addition of equal amount of EtOAc and about 250 mg Na2CO3 in a separatory funnel. The phases were separated and the organic washed with brine, dried over MgSO4, filtered and concentrated in vacuo to yield (S)-1-(3-phenoxyphenyl)ethanamine (361.5 mg, 1.678 mmol, 50.5% yield) as an amber oil. LCMS m/z 214.1 (M+H)+, Rt 0.61 min. The tube was flushed with N2 capped The heterogenous mixture was diluted with EtOAc filtered through a glass-fritted funnel eluting with EtOAc The volatiles were then removed in vacuo the crude brown liquid was filtered through 1 um PTFE filter purified by reverse phase HPLC The combined product fractions were desalted by addition of equal amount of EtOAc and about 250 mg Na2CO3 in a separatory funnel The phases were separated the organic washed with brine dried over MgSO4 filtered concentrated in vacuo

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

Procedure: Commercially available (S)-1-(3-bromophenyl)ethanamine (1.0 g, 5 mmol) was dissolved in THF (20 mL). Pyridine (0.5 mL) and acetic anhydride (0.51 g, 5 mmol) were added and the reaction mixture allowed to stir at room temperature overnight. The solvent was removed under reduced pressure to provide A4a.1 (1.23 g) as a clear yellowish liquid. (M+H)+=242.15, 244.16. The solvent was removed under reduced pressure to provide A4a.1 (1.23 g) as a clear yellowish liquid

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 20 ml microwave vial was weighted 1-(pyridin-2-yl)propan-2-one ligand (90 mg, 0.665 mmol), phenol (407 mg, 4.32 mmol), CuBr (47.7 mg, 0.332 mmol) and Cs2CO3 (2166 mg, 6.65 mmol). To the mixture was added DMSO (5 ml) and (S)-1-(3-bromophenyl)ethanamine (0.5 ml, 3.32 mmol). The tube was flushed with N2, capped, and the black mixture heated in the oil bath at 90° C. for 18 hours. The heterogenous mixture was diluted with EtOAc and filtered through a glass-fritted funnel, eluting with EtOAc and another 5 mls of DMSO. The volatiles were then removed in vacuo and the crude brown liquid was filtered through 1 um PTFE filter and purified by reverse phase HPLC. The combined product fractions were desalted by addition of equal amount of EtOAc and about 250 mg Na2CO3 in a separatory funnel. The phases were separated and the organic washed with brine, dried over MgSO4, filtered and concentrated in vacuo to yield (S)-1-(3-phenoxyphenyl)ethanamine (361.5 mg, 1.678 mmol, 50.5% yield) as an amber oil. LCMS m/z 214.1 (M+H)+, Rt 0.61 min. The tube was flushed with N2 capped The heterogenous mixture was diluted with EtOAc filtered through a glass-fritted funnel eluting with EtOAc The volatiles were then removed in vacuo the crude brown liquid was filtered through 1 um PTFE filter purified by reverse phase HPLC The combined product fractions were desalted by addition of equal amount of EtOAc and about 250 mg Na2CO3 in a separatory funnel The phases were separated the organic washed with brine dried over MgSO4 filtered concentrated in vacuo

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

Procedure: To a solution of 1-(4-(1-(methoxycarbonyl)cyclopropyl)benzyl)-2,3-dimethyl-1H-indole-5-carboxylic acid (50 mg, 0.13 mmol) in DMF (1 mL) was added (S)-1-(3-bromophenyl)ethylamine (21 μL), DIEA (45 μL) and HATU (54 mg). The reaction mixture was allowed to stir at rt for 30 min, and then was diluted by ethyl acetate. The resulting mixture was washed with a 0.5 N HCl solution, a saturated solution of NaHCO3, and brine, dried on MgSO4, and concentrated to afford a yellow oil (73 mg) which was directly used without further purification. The resulting mixture was washed with a 0.5 N HCl solution a saturated solution of NaHCO3, and brine, dried on MgSO4 concentrated

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 20 ml microwave vial was weighted 1-(pyridin-2-yl)propan-2-one ligand (90 mg, 0.665 mmol), phenol (407 mg, 4.32 mmol), CuBr (47.7 mg, 0.332 mmol) and Cs2CO3 (2166 mg, 6.65 mmol). To the mixture was added DMSO (5 ml) and (S)-1-(3-bromophenyl)ethanamine (0.5 ml, 3.32 mmol). The tube was flushed with N2, capped, and the black mixture heated in the oil bath at 90° C. for 18 hours. The heterogenous mixture was diluted with EtOAc and filtered through a glass-fritted funnel, eluting with EtOAc and another 5 mls of DMSO. The volatiles were then removed in vacuo and the crude brown liquid was filtered through 1 μm PTFE filter and purified by reverse phase HPLC. The combined product fractions were desalted by addition of equal amount of EtOAc and about 250 mg Na2CO3 in a separatory funnel. The phases were separated and the organic washed with brine, dried over MgSO4, filtered and concentrated in vacuo to yield (S)-1-(3-phenoxyphenyl)ethanamine (361.5 mg, 1.678 mmol, 50.5% yield) as an amber oil. LCMS m/z 214.1 (M+H)+, Rt 0.61 min. The tube was flushed with N2 capped The heterogenous mixture was diluted with EtOAc filtered through a glass-fritted funnel eluting with EtOAc The volatiles were then removed in vacuo the crude brown liquid was filtered through 1 μm PTFE filter purified by reverse phase HPLC The combined product fractions were desalted by addition of equal amount of EtOAc and about 250 mg Na2CO3 in a separatory funnel The phases were separated the organic washed with brine dried over MgSO4 filtered concentrated in vacuo

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

Procedure: Intermediate 34 was prepared according to the procedures described in Intermediate 33 using (S)-1-(3-bromophenyl)ethanamine as the starting material. LC-MS (ESI) m/z 340.0 (M+H), RT=1.64 min (Method B).