(4-bromo-3-fluorophenyl)boronic acid

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

Procedure: 4-Bromo-3-fluorophenyl boronic acid (28AB) (1.0 g, 4.57 mmol, 1 equiv), 2-bromopyrimidine (1AB) (2.18 g, 13.7 mmol, 3 equiv), and 2M sodium carbonate (12 mL) were added in a pressure vessel (150 mL) and a (1v:1v) mixture of toluene and ethanol (25 mL: 25 mL) was added. The mixture was then bubbled with nitrogen gas for about 10 minutes. Tetrakistriphenylphosphine palladium (0) (266 mg, 0.23 mmol, 0.05 equiv) was added to the mixture. The reaction vessel was tightly capped, placed in an oil bath at 90° C., and stirred overnight. was added The mixture was then bubbled with nitrogen gas for about 10 minutes The reaction vessel was tightly capped placed in an oil bath at 90° C.

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromopyrimidin-2-amine (2.1 g, 0.012 mol) in 1,4-dioxane (30 mL) was added (4-bromo-3-fluorophenyl)boronic acid (2.0 g, 0.0091 mol), potassium phosphate (6.4 g, 0.030 mol) and tetrakis(triphenylphosphine)palladium (700 mg, 0.6 mmol), water (5 mL). The solution was degassed with N2, and heated at 120° C. for 4 h. The mixture was cooled to RT, poured into water, and extracted with EtOAc. The combined organic layers were washed with brine, dried with MgSO4, filtered, and concentrated. The residue was purified by chromatography on silica gel with EtOAc in CH2Cl2 (0-30%) to afford the desired compound. LCMS: (M+H)=267.9. The solution was degassed with N2 The mixture was cooled to RT poured into water extracted with EtOAc The combined organic layers were washed with brine dried with MgSO4 filtered concentrated The residue was purified by chromatography on silica gel with EtOAc in CH2Cl2 (0-30%)

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

Procedure: The title compound was prepared from 5-bromo-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine, 4-bromo-3-fluoro-phenyl boronic acid, and dimethylphosphine oxide following the same procedures as Example 1 Step 1 and Step 3; ESMS: m/z 471 (M+H)+.

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

Procedure: In accordance with Example 4-(2), but using tert-butyl[(4-iodobenzyl)oxy]dimethylsilane instead of tert-butyl[2-(4-iodophenyl)ethoxy]dimethylsilane, and (4-bromo-3-fluorophenyl)boronic acid instead of (4-bromophenyl)boronic acid, the title compound (yield 73%) was afforded as a white solid.

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromopyrimidin-2-amine (2.1 g, 0.012 mol) in 1,4-dioxane (30 mL) was added (4-bromo-3-fluorophenyl)boronic acid (2.0 g, 0.0091 mol), potassium phosphate (6.4 g, 0.030 mol) and tetrakis(triphenylphosphine)palladium (700 mg, 0.6 mmol), water (5 mL). The solution was degassed with N2, and heated at 120° C. for 4 h. The mixture was cooled to RT, poured into water, and extracted with EtOAc. The combined organic layers were washed with brine, dried with MgSO4, filtered, and concentrated. The residue was purified by chromatography on silica gel with EtOAc in CH2Cl2 (0-30%) to afford the desired compound. LCMS: (M+H)=267.9. The solution was degassed with N2 The mixture was cooled to RT poured into water extracted with EtOAc The combined organic layers were washed with brine dried with MgSO4 filtered concentrated The residue was purified by chromatography on silica gel with EtOAc in CH2Cl2 (0-30%)

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

Procedure: 4-Bromo-3-fluorophenyl boronic acid (28AB) (1.0 g, 4.57 mmol, 1 equiv), 2-bromopyrimidine (1AB) (2.18 g, 13.7 mmol, 3 equiv), and 2M sodium carbonate (12 mL) were added in a pressure vessel (150 mL) and a (1v:1v) mixture of toluene and ethanol (25 mL: 25 mL) was added. The mixture was then bubbled with nitrogen gas for about 10 minutes. Tetrakistriphenylphosphine palladium (0) (266 mg, 0.23 mmol, 0.05 equiv) was added to the mixture. The reaction vessel was tightly capped, placed in an oil bath at 90° C., and stirred overnight. was added The mixture was then bubbled with nitrogen gas for about 10 minutes The reaction vessel was tightly capped placed in an oil bath at 90° C.

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromopyrimidin-2-amine (2.1 g, 0.012 mol) in 1,4-dioxane (30 mL) was added (4-bromo-3-fluorophenyl)boronic acid (2.0 g, 0.0091 mol), potassium phosphate (6.4 g, 0.030 mol) and tetrakis(triphenylphosphine)palladium (700 mg, 0.6 mmol), water (5 mL). The solution was degassed with N2, and heated at 120° C. for 4 h. The mixture was cooled to RT, poured into water, and extracted with EtOAc. The combined organic layers were washed with brine, dried with MgSO4, filtered, and concentrated. The residue was purified by chromatography on silica gel with EtOAc in CH2Cl2 (0-30%) to afford the desired compound. LCMS: (M+H)=267.9. The solution was degassed with N2 The mixture was cooled to RT poured into water extracted with EtOAc The combined organic layers were washed with brine dried with MgSO4 filtered concentrated The residue was purified by chromatography on silica gel with EtOAc in CH2Cl2 (0-30%)