3,5-dibromoaniline

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

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

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

Procedure: A solution of 3,5-dibromoaniline (2.93 g, 11.67 mmol), 2-chloro-4-methylpyrimidine (1.5 g, 11.67 mmol), and acetic acid (0.701 mL, 12.25 mmol) in 1,4-dioxane (23.5 mL) was sealed in a pressure vessel under an argon atmosphere and heated at 120° C. for 17 hours. After being cooled to room temperature, the reaction mixture was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (40 mL). The layers were separated, and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. Silica gel flash chromatography (10% to 30% ethyl acetate/hexanes) afforded N-(3,5-dibromophenyl)-4-methylpyrimidin-2-amine (3.6 g, 9.97 mmol, 85% yield, 95% purity) as a light yellow solid. MS ESI: [M+H]+ m/z 343.8. After being cooled to room temperature the reaction mixture was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (40 mL) The layers were separated the organic layer was washed with brine dried over sodium sulfate filtered concentrated

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The mixture of 3,5-dibromoaniline (1.16 g, 4.6 mmol), pyrazole (0.47 g, 6.9 mmol), Fe(acac)3 (0.35 g, 1.0 mmol), Cu(OAc)2.H2O (0.18 g, 1.0 mmol) and cesium carbonate (3.00 g, 9.2 mmol) in 20 mL DMF was stirred at 135° C. in a sealed tube for 3 days. The mixture was diluted with EtOAc, stirred vigorously, filtered through celite, concentrated in vacuo, subjected to silica flash column to isolate 3,5-di(1H-pyrazol-1-yl)aniline and 3-bromo-5-(1H-pyrazol-1-yl)aniline (0.52 g). stirred vigorously filtered through celite concentrated in vacuo

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

Procedure: The mixture of 3,5-dibromoaniline (1.05 g, 4.2 mmol), 2-tributylstannylpyrimidine (5.00 g, 13.6 mmol), Pd(Ph3P)4 (0.97 g, 0.84 mmol) in 60 mL toluene was degassed with argon stream and stirred at 110° C. in argon atmosphere for three days. It was cooled to RT, diluted with EtOAc, filtered through celite, concentrated in vacuo, and subjected to silica flash column to isolate 3,5-di(pyrimidin-2-yl)aniline and 3-bromo-5-(pyrimidin-2-yl)aniline. was degassed with argon stream It was cooled to RT diluted with EtOAc filtered through celite concentrated in vacuo

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

Procedure: A solution of 3,5-dibromoaniline (2.93 g, 11.67 mmol), 2-chloro-4-methylpyrimidine (1.5 g, 11.67 mmol), and acetic acid (0.701 mL, 12.25 mmol) in 1,4-dioxane (23.5 mL) was sealed in a pressure vessel under an argon atmosphere and heated at 120° C. for 17 hours. After being cooled to room temperature, the reaction mixture was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (40 mL). The layers were separated, and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. Silica gel flash chromatography (10% to 30% ethyl acetate/hexanes) afforded N-(3,5-dibromophenyl)-4-methylpyrimidin-2-amine (3.6 g, 9.97 mmol, 85% yield, 95% purity) as a light yellow solid. MS ESI: [M+H]+ m/z 343.8. After being cooled to room temperature the reaction mixture was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (40 mL) The layers were separated the organic layer was washed with brine dried over sodium sulfate filtered concentrated

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

Procedure: A solution of 3,5-dibromoaniline (2.93 g, 11.67 mmol), 2-chloro-4-methylpyrimidine (1.5 g, 11.67 mmol), and acetic acid (0.701 mL, 12.25 mmol) in 1,4-dioxane (23.5 mL) was sealed in a pressure vessel under an argon atmosphere and heated at 120° C. for 17 hours. After being cooled to room temperature, the reaction mixture was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (40 mL). The layers were separated, and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. Silica gel flash chromatography (10% to 30% ethyl acetate/hexanes) afforded N-(3,5-dibromophenyl)-4-methylpyrimidin-2-amine (3.6 g, 9.97 mmol, 85% yield, 95% purity) as a light yellow solid. MS ESI: [M+H]+ m/z 343.8. After being cooled to room temperature the reaction mixture was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (40 mL) The layers were separated the organic layer was washed with brine dried over sodium sulfate filtered concentrated

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

Procedure: To a solution of 3,5-dibromoaniline (0.50 g, 1.99 mmol) in DMSO (2.0 mL) was added sequentially L-Proline (0.041 g, 0.36 mmol), Cs2CO3 (1.16 g, 3.58 mmol), CuI (0.038 g, 0.20 mmol) and pyrazole (0.12 g, 1.80 mmol). The reaction mixture was degassed for 10 min and then heated to 110° C. for 48 h. After the completion of reaction (TLC monitoring), the reaction mixture was cooled to room temperature, added water and extracted with ethyl acetate (×3). The combined organics was washed with water, dried (Na2SO4), filtered and concentrated. The residue was purified over silica gel (230-400 M, 15% EtOAc-Hexane) to get the desired compound (0.18 g, 37%). The reaction mixture was degassed for 10 min After the completion of reaction (TLC monitoring) the reaction mixture was cooled to room temperature extracted with ethyl acetate (×3) The combined organics was washed with water dried (Na2SO4) filtered concentrated The residue was purified over silica gel (230-400 M, 15% EtOAc-Hexane)

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

Procedure: To the solution of 3,5-dibromoaniline (65.0 g, 0.26 mol) in anhydrous acetone (1.6 L) was added benzoylisothiocyanate (46.4 g, 0.28 mol) and the reaction mixture was stirred at room temperature for 30 min. Acetone was distilled off and the crude residue was washed with hexane to obtain desired compound as yellow solid (96.5 g, 90%). Acetone was distilled off the crude residue was washed with hexane

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

Procedure: To the solution of 3,5-dibromoaniline (65.0 g, 0.26 mol) in anhydrous acetone (1.6 L) was added benzoylisothiocyanate (46.4 g, 0.28 mol) and the reaction mixture was stirred at room temperature for 30 min. Acetone was distilled off and the crude residue was washed with hexane to obtain desired compound as yellow solid (96.5 g, 90%). Acetone was distilled off the crude residue was washed with hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1,3-dibromo-5-nitro-benzene (85.0 g, 0.30 mol) in 1 L of ethanol was added SnCl2.2H2O (341.0 g, 1.50 mol) portion wise at room temperature. The reaction mixture was heated under reflux at 80° C. for 1.5 h. After cooling to room temperature, the solvent was evaporated under reduced pressure and the crude white solid thus obtained was basified with 4N NaOH solution to pH 12. The mixture was extracted with ethyl acetate (×3) and the combined organic layer was washed with brine solution and dried over Na2SO4. The solvent was removed under reduced pressure, to give the desired compound as a brown solid (65.0 g, 86%). The reaction mixture was heated After cooling to room temperature the solvent was evaporated under reduced pressure the crude white solid thus obtained The mixture was extracted with ethyl acetate (×3) the combined organic layer was washed with brine solution dried over Na2SO4 The solvent was removed under reduced pressure

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

Procedure: 3,5-dibromoaniline was treated as described in the procedure for 2-(3'-bromophenyl)thiophene to give 2-(3',5'-dibromophenyl)thiophene in 55% yield as a yellow oil, which solidified as a glassy solid.