2-Chloro-4-(trifluoromethyl)phenylboronic acid

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 5-bromo-4-methyl-1H-pyrrole-3-carboxylate (0.44 g, 2.0 mmol), [4-chloro-2-(trifluoromethyl)phenyl]boronic acid (0.90 g, 4.0 mmol), Na2CO3 (0.64 g, 6.0 mmol) and palladium tetrakis(triphenylphosphine) (0.12 g, 0.10 mmol) in toluene/water (9:1, 10 ml) was stirred at 110° C. for 2.0 h under N2. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The mixture was washed with water and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (dichloromethane) to give the title compound (0.41 g, 65%) as a pale yellow solid. The reaction mixture was cooled to room temperature The mixture was washed with water and brine dried over sodium sulfate concentrated on a rotary evaporator The resulting residue was purified by silica-gel column chromatography (dichloromethane)

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

Procedure: The title compound was prepared from 2-(5-bromo-1-methyl-1H-imidazol-4-yl)pyridine-4-carbonitrile and 4-chloro-2-trifluoromethylphenylboronic acid according to the procedure for the preparation of Example 3, part A. [M+H] Calc'd for C17H10ClF3N4, 364. Found, 363, 365.

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

Procedure: The title compound was prepared from 2-(5-bromo-1-methyl-1H-imidazol-4-yl)pyridine-4-carbonitrile and 4-chloro-2-trifluoromethylphenylboronic acid according to the procedure for the preparation of Example 3, part A. [M+H] Calc'd for C17H10ClF3N4, 364. Found, 363, 365.

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-chloro-4-iodo-2-nitroaniline (2 g, 6.70 mmol) in dioxane (100 ml) and water (10 ml) which maintained with an inert atmosphere of nitrogen was added [4-chloro-2-(trifluoromethyl)phenyl]boronic acid (1.8 g, 8.02 mmol), K3PO4 (2.6 g, 12.24 mmol), Pd(PPH3)4 (0.78 g, 335.77 mmol) with stirring overnight at 95° C. in an oil bath. The resulting mixture was concentrated under vacuum to give a residue which was purified by a silica gel column, eluting with 2% to 3% acetate in petroleum ether to produce 5-chloro-4-[4-chloro-2-(trifluoromethyl)phenyl]-2-nitroaniline as a yellow solid (800 mg, 34%). Next, to a solution of 5-chloro-4-[4-chloro-2-(trifluoromethyl)phenyl]-2-nitroaniline (1.6 g, 4.56 mmol) in ethanol (50 ml) was added Zn powder (1.8 g, 27.69 mmol), hydrogen chloride (2 ml) with stirring for 2 h at 85° C. in an oil bath. The solution was poured into water (300 ml), adjusted to pH 8 with saturated aqueous sodium carbonate and extracted with ethyl acetate (3×100 ml). The combined organic layers were washed with brine (100 ml), dried over anhydrous sodium sulfate and concentrated under vacuum to give a residue, which was purified by a silica gel column, eluting with 5% to 20% ethyl acetate in petroleum to produce 4-chloro-5-[4-chloro-2-(trifluoromethyl)phenyl]benzene-1,2-diamine as a crude red solid (560 mg, 76%). Finally, the solution of 4-chloro-5-[4-chloro-2-(trifluoromethyl)phenyl]benzene-1,2-diamine (100 mg, 0.31 mmol) in trifluoroacetic acid (5 m 1) and hydrogen chloride (1 ml) was stirred overnight at 80° C. in an oil bath. The mixture was quenched with water (100 ml), adjusted to pH 8 with saturated aqueous sodium carbonate solution and extracted with ethyl acetate (50 ml×3). The organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum to give a residue, which was purified by a silica gel column with 10% ethyl acetate in petroleum ether to afford 5-chloro-6-[4-chloro-2-(trifluoromethyl)phenyl]-2-(trifluoro methyl)-1H-1,3-benzodiazole as a white solid (101.7 mg, 82%). The resulting mixture was concentrated under vacuum to give a residue which was purified by a silica gel column eluting with 2% to 3% acetate in petroleum ether

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 5-bromo-4-methyl-1H-pyrrole-3-carboxylate (0.44 g, 2.0 mmol), [4-chloro-2-(trifluoromethyl)phenyl]boronic acid (0.90 g, 4.0 mmol), Na2CO3 (0.64 g, 6.0 mmol) and palladium tetrakis(triphenylphosphine) (0.12 g, 0.10 mmol) in toluene/water (9:1, 10 ml) was stirred at 110° C. for 2.0 h under N2. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The mixture was washed with water and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (dichloromethane) to give the title compound (0.41 g, 65%) as a pale yellow solid. The reaction mixture was cooled to room temperature The mixture was washed with water and brine dried over sodium sulfate concentrated on a rotary evaporator The resulting residue was purified by silica-gel column chromatography (dichloromethane)