2-(2,4-dichlorophenoxy)ethanamine

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

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

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

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

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: A solution of 2-(2,4-Dichloro-phenoxy)-ethylamine 29 (19 mg, 0.09 mmol) in toluene (0.2 mL) is cooled to 0° C. The above solution of intermediate 61 (0.06 mmol) is added and the solution is warmed to room temperature. After stirring at room temperature for 1 hour the mixture is poured into H2O and extracted three times with DCM. The organic layers are combined, dried (MgSO4), filtered, and concentrated to afford crude (3-Chloro-4-{4-[2-(2,4-dichloro-phenoxy)-ethyl-carbamoyl]-3-phenyl-isoxazol-5-yl}-phenyl)-acetic acid methyl ester 62. extracted three times with DCM dried (MgSO4) filtered concentrated

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(2,4-Dichloro-phenoxy)-ethylamine 29 (412 mg, 2.0 mmol) in toluene (1.5 mL) is added ethyl benzoylacetate 34 (384 mg, 2.0 mmol). The mixture is heated to 160° C. for 10 minutes in a microwave. The resulting mixture is concentrated and purified on reverse phase HPLC (H2O/MeCN gradient) to afford N-[2-(2,4-dichloro-phenoxy)-ethyl]-3-oxo-3-phenyl-propionamide 35 as a white solid: 1H-NMR (400 MHz, CDCl3) δ=7.98 (d, J=7.2 Hz, 2H), 7.60-7.35 (m, 5H), 7.15 (dd, J=2.5 Hz, J=8.8 Hz, 1H), 6.83 (d, J=8.8 Hz, 1H), 4.10 (t, J=5.2 Hz, 2H), 3.98 (s, 2H), 3.76 (q, J=5.3 Hz, 2H). MS calculated for C17H16Cl2NO3 (M+H+) 352.0, found 352.1. The resulting mixture is concentrated purified on reverse phase HPLC (H2O/MeCN gradient)

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

Procedure: A solution of 2-(2,4-Dichloro-phenoxy)-ethylamine 29 (17 mg, 0.08 mmol) in toluene (2 mL) is cooled to 0° C. A solution of intermediate 26 (0.08 mmol) and triethylamine (23 μL, 0.16 mmol) in MeCN (1 mL) is added and the solution is warmed to room temperature. After stirring at room temperature for 1 h the mixture is poured into H2O and extracted three times with EtOAc. The organic layers are combined, dried (MgSO4), filtered, and concentrated to afford crude (3-Chloro-4-{4-[2-(2,4-dichloro-phenoxy)-ethylcarbamoyl]-5-methyl-isoxazol-3-yl}-phenyl)-acetic acid methyl ester 30. extracted three times with EtOAc dried (MgSO4) filtered concentrated