5-bromo-2-(trifluoromethoxy)aniline

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: Pd2(dba)3 (1.1 g, 1.2 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)-biphenyl (0.94 g, 2.4 mmol), 5-bromo-2-trifluoromethoxy-phenylamine (30.7 g, 120 mmol) in THF (50 mL) were charged in a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. LiN(TMS)2 solution (1M in THF, 288 mL) and N-methylpiperazine (26.7 mL, 194 mmol) were added and the reaction refluxed for 1 hours. The reaction mixture was then allowed to cool to room temperature and filtered through a pad of celite. The organic phase was concentrated, the residue dissolved in DCM (200 mL) and washed with H2O (1×100 mL). The organic phases were dried over anhydrous Na2SO4, the solvent evaporated in vacuo and the crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10) to afford 23 g of 4-(4-methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamine (70% yield) as a light brown powder. flushed with argon The flask was evacuated the reaction refluxed for 1 hours filtered through a pad of celite The organic phase was concentrated the residue dissolved in DCM (200 mL) washed with H2O (1×100 mL) The organic phases were dried over anhydrous Na2SO4 the solvent evaporated in vacuo the crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10)

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

Procedure: Pd2(dba)3 (1.1 g, 1.2 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)-biphenyl (0.94 g, 2.4 mmol), 5-bromo-2-trifluoromethoxy-phenylamine (30.7 g, 120 mmol) in THF (50 mL) were charged in a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. LiN(TMS)2 solution (1M in THF, 288 mL) and N-methylpiperazine (26.7 mL, 194 mmol) were added and the reaction refluxed for 1 hours. The reaction mixture was then allowed to cool to room temperature and filtered through a pad of celite. The organic phase was concentrated, the residue dissolved in DCM (200 mL) and washed with H2O (1×100 mL). The organic phases were dried over anhydrous Na2SO4, the solvent evaporated in vacuo and the crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10) to afford 23 g of 4-(4-methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamine (70% yield) as a light brown powder. flushed with argon The flask was evacuated the reaction refluxed for 1 hours filtered through a pad of celite The organic phase was concentrated the residue dissolved in DCM (200 mL) washed with H2O (1×100 mL) The organic phases were dried over anhydrous Na2SO4 the solvent evaporated in vacuo the crude solid was purified by flash chromatography on silica gel (eluant: DCM/EtOH 90/10)

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: To a solution of 2-trifluoromethoxy-5-bromo-phenylamine (5.12 g, 20 mmol) in EtOH (50 mL) at 0° C. was added a solution of acetic anhydride (4.7 mL, 50 mmol) in EtOH (10 mL). The mixture was stirred at room temperature overnight. The solvent was evaporated to dryness and the solid was tritured with diethyl ether and filtered to give 5.64 g (95% yield) of N-(5-bromo-2-trifluoromethoxy-phenyl)-acetamide. The solvent was evaporated to dryness filtered

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

Procedure: Palladium acetate [Pd(OAc)2] (0.12 g, 0.55 mmol), (±)-BINAP (0.34 g, 0.55 mmol) and dimethylformamide (60 mL) were charged to a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. The mixture was stirred under argon for 30 minutes and added to a mixture of 5-bromo-2-trifluoromethoxy aniline (2.0 g, 5.60 mmol), 5-(2-iodo-pyrimidin-4-yl)-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (1.44 g, 5.60 mmol), and potassium carbonate (7.70 g, 55.80 mmol) in dimethylformamide (90 mL). The resulting mixture was stirred at 80° C. for 3 hours under argon. After cooling to room temperature, the reaction mixture was filtered on a pad of celite. The solvent was concentrated, the crude solid was purified by flash chromatography on silica gel (eluant: hexane/ethyl acetate 70/30) to afford 1.41 g (52%) of the title compound as white solid. flushed with argon The flask was evacuated The resulting mixture was stirred at 80° C. for 3 hours under argon the reaction mixture was filtered on a pad of celite The solvent was concentrated the crude solid was purified by flash chromatography on silica gel (eluant: hexane/ethyl acetate 70/30)