2-bromo-3-methylbenzaldehyde

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-iodopyrazine (0.48 mL, 4.85 mmol) in dry THF (3 mL) was brought to 0° C. followed by the slowly addition of butylmagnesium chloride, 2.0M solution in THF (2.4 mL, 4.85 mmol). The resulting dark solution was stirred at 0° C. for 30 min then a solution of 2-bromo-3-methylbenzaldehyde (1.06 g, 5.34 mmol) in THF (2 mL) was slowly added and kept at 0° C. for 2 h. The mixture was quenched with saturated NH4Cl and extracted with DCM. The combined organics were washed with brine, dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography using gradient 1:1 hexanes/EtOAc to afford a yellow-orange oil as (2-bromo-3-methylphenyl)(pyrazin-2-yl)methanol. was brought to 0° C. kept at 0° C. for 2 h The mixture was quenched with saturated NH4Cl extracted with DCM The combined organics were washed with brine dried over Na2SO4 filtered concentrated purified by silica gel column chromatography

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

Procedure: To a mixture of 4-chloro-2-(methylthio)pyrimidine (0.36 mL, 3.11 mmol), 2-bromo-3-methylbenzaldehyde (0.744 g, 3.74 mmol), and 1,3-dimethyl-1H-imidazol-3-ium iodide (0.697 g, 3.11 mmol) in THF (3 mL) was added NaH (0.149 g, 3.74 mmol) and the resulting mixture was refluxed for 30 min. Product was observed and the reaction went to completion. The mixture was brought to RT and poured into ice-water, extracted with DCM and purified using hexanes to afford a light yellow solid as (2-bromo-3-methylphenyl)(2-(methylthio)pyrimidin-4-yl)methanone. the resulting mixture was refluxed for 30 min was brought to RT extracted with DCM purified

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-3-methylbenzaldehyde (0.30 g, 1.51 mmol), tris(dibenzylidenacetone)dipalladium (0) (0.055 g, 0.060 mmol), 2-(dicyclohexylphosphino)biphenyl (0.032 g, 0.091 mmol), tripotassium phosphate (0.64 g, 3.0 mmol), 3-(methoxycarbonylphenyl)boronic acid (0.35 g, 1.96 mmol) and toluene (6 mL) was stirred under an argon atmosphere at 90° C. for 17 hrs. The reaction mixture was cooled, diluted with ethyl acetate, washed with water and saturated brine, dried (anhydrous sodium sulfate), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-hexane/ethyl acetate=4/1) to give the title compound (0.25 g, yield 65%) as a yellow oil. The reaction mixture was cooled washed with water and saturated brine dried (anhydrous sodium sulfate) concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane-hexane/ethyl acetate=4/1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-iodopyrazine (0.48 mL, 4.85 mmol) in dry THF (3 mL) was brought to 0° C. followed by the slowly addition of butylmagnesium chloride, 2.0M solution in THF (2.4 mL, 4.85 mmol). The resulting dark solution was stirred at 0° C. for 30 min then a solution of 2-bromo-3-methylbenzaldehyde (1.06 g, 5.34 mmol) in THF (2 mL) was slowly added and kept at 0° C. for 2 h. The mixture was quenched with saturated NH4Cl and extracted with DCM. The combined organics were washed with brine, dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography using gradient 1:1 hexanes/EtOAc to afford a yellow-orange oil as (2-bromo-3-methylphenyl)(pyrazin-2-yl)methanol. was brought to 0° C. kept at 0° C. for 2 h The mixture was quenched with saturated NH4Cl extracted with DCM The combined organics were washed with brine dried over Na2SO4 filtered concentrated purified by silica gel column chromatography

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

Procedure: To a mixture of 4-chloro-2-(methylthio)pyrimidine (0.36 mL, 3.11 mmol), 2-bromo-3-methylbenzaldehyde (0.744 g, 3.74 mmol), and 1,3-dimethyl-1H-imidazol-3-ium iodide (0.697 g, 3.11 mmol) in THF (3 mL) was added NaH (0.149 g, 3.74 mmol) and the resulting mixture was refluxed for 30 min. Product was observed and the reaction went to completion. The mixture was brought to RT and poured into ice-water, extracted with DCM and purified using hexanes to afford a light yellow solid as (2-bromo-3-methylphenyl)(2-(methylthio)pyrimidin-4-yl)methanone. the resulting mixture was refluxed for 30 min was brought to RT extracted with DCM purified