4-bromo-2-fluoro-5-(trifluoromethoxy)aniline

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

Procedure: To a solution of 4-bromo-2-fluoro-5-trifluoromethoxy-phenylamine (500 mg, 2 mmol) dissolved in DCM (1 mL) was slowly added a solution of 2-fluoropyridine-5-carbonyl chloride (290 mg, 1.8 mmol) in DCM (1 mL). A few drops of DMA were added and the reaction mixture was concentrated to form N-(4-bromo-2-fluoro-5-trifluoromethoxy-phenyl)-6-fluoro-nicotinamide as a purple solid. the reaction mixture was concentrated

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

Procedure: To a mixture of 2-fluoro-5-(trifluoromethoxy)aniline (1 g, 5 mmol) dissolved in DMF (2 mL) was slowly added a solution of N-bromosuccinimide (1.1 g, 6.2 mmol) dissolved in DMF (2 mL). The reaction mixture was stirred at room temperature for 1 h, concentrated and extracted with ethyl acetate/water. The organic layer was dried over sodium sulfate, filtered, concentrated and purified by silica gel chromatography (eluted 0-10% ethyl acetate:hexanes) to produce the title intermediate as a red oil (818 mg, 58% yield). (m/z): [M+H]+ calcd for C7H4BrF4NO 273.94, 275.94. found 276.1. concentrated extracted with ethyl acetate/water The organic layer was dried over sodium sulfate filtered concentrated purified by silica gel chromatography (eluted 0-10% ethyl acetate:hexanes)

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

Procedure: To a mixture of 2-fluoro-5-(trifluoromethoxy)aniline (2 g, 10 mmol) dissolved in DMF (4 mL) was slowly added a solution of N-bromosuccinimide (2.2 g, 12 mmol) dissolved in DMF (5 mL). The reaction mixture was stirred at RT for 1 h, concentrated and extracted with ethyl acetate/water. The organic layer was washed with brine, partitioned, dried over sodium sulfate, filtered, concentrated, and purified by silica chromatography (100% hexanes) to produce the title intermediate as a red oil (2 g, 70% yield). (m/z): [M+H]+ calcd for C7H4BrF4NO 273.94; 275.94. found 276.2. concentrated extracted with ethyl acetate/water The organic layer was washed with brine partitioned dried over sodium sulfate filtered concentrated purified by silica chromatography (100% hexanes)

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

Procedure: To a solution of 4-bromo-2-fluoro-5-trifluoromethoxy-phenylamine (500 mg, 2 mmol) dissolved in DCM (1 mL) was slowly added a solution of 2-fluoropyridine-5-carbonyl chloride (290 mg, 1.8 mmol) in DCM (1 mL). A few drops of DMA were added and the reaction mixture was concentrated to form N-(4-bromo-2-fluoro-5-trifluoromethoxy-phenyl)-6-fluoro-nicotinamide as a purple solid. the reaction mixture was concentrated

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

Procedure: To a solution of 4-bromo-2-fluoro-5-trifluoromethoxy-phenylamine (500 mg, 2 mmol) dissolved in DCM (1 mL) was slowly added a solution of 2-fluoropyridine-5-carbonyl chloride (290 mg, 1.8 mmol) in DCM (1 mL). A few drops of DMA were added and the reaction mixture was concentrated to form N-(4-bromo-2-fluoro-5-trifluoromethoxy-phenyl)-6-fluoro-nicotinamide as a purple solid. the reaction mixture was concentrated

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

Procedure: To a mixture of 2-fluoro-5-(trifluoromethoxy)aniline (1 g, 5 mmol) dissolved in DMF (2 mL) was slowly added a solution of N-bromosuccinimide (1.1 g, 6.2 mmol) dissolved in DMF (2 mL). The reaction mixture was stirred at room temperature for 1 h, concentrated and extracted with ethyl acetate/water. The organic layer was dried over sodium sulfate, filtered, concentrated and purified by silica gel chromatography (eluted 0-10% ethyl acetate:hexanes) to produce the title intermediate as a red oil (818 mg, 58% yield). (m/z): [M+H]+ calcd for C7H4BrF4NO 273.94, 275.94 found 276.1. concentrated extracted with ethyl acetate/water The organic layer was dried over sodium sulfate filtered concentrated purified by silica gel chromatography (eluted 0-10% ethyl acetate:hexanes)