2-溴-4-氟-1-甲磺酰苯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-bromo-4-fluoro-1-(methylsulfonyl)benzene (117 mg, 0.46 mmol), bis(pinacolato)diboron (123 mg, 0.48 mmol), potassium acetate (135 mg, 1.38 mmol) and bis(diphenylphosphino)-ferrocenedichloropalladium(II)-DCM-complex (19 mg, 0.02 mmol) in dioxane (1.5 mL) were irradiated in a Biotage microwave for 60 min at 120° C. (S)-1-(4-(6-chloro-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)-3-ethylurea (Intermediate 2) (173 mg, 0.46 mmol), sodium carbonate solution (2M aqueous solution, 0.92 mL, 1.84 mmol) and EtOH (0.3 mL) were added and reaction mixture further irradiated in a Biotage microwave for 60 min at 100° C. The reaction mixture was concentrated in vacuo, and the residue suspended in EtOAc (70 mL), washed with water (2×40 mL) followed by brine (40 mL), dried with sodium sulfate and concentrated in vacuo to leave an orange oil. The oil was purified by flash chromatography (0-20% EtOAc in DCM over 60 min) to yield the title compound as an orange solid (80 mg, 34%). were added reaction mixture further irradiated in a Biotage microwave for 60 min at 100° C The reaction mixture was concentrated in vacuo washed with water (2×40 mL) dried with sodium sulfate concentrated in vacuo to leave an orange oil The oil was purified by flash chromatography (0-20% EtOAc in DCM over 60 min)

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium hydrogen carbonate (1.59 g, 18.87 mmol) and sodium sulfite (1.59 g, 12.58 mmol) were heated in water (10 mL) at 70° C. for 5 min. A mixture of 2-bromo-4-fluoro-benzene sulfonyl chloride (1.72 g, 6.29 mmol) in dioxane (15 mL) was added to the base solution and stirred at 70° C. overnight. The solvents were removed in vacuo, DMF (15 mL) and methyl iodide (0.43 mL, 6.85 mmol) were added and reaction mixture stirred at 40° C. overnight. The reaction mixture was concentrated in vacuo, EtOAc (10 ml) added, washed with water (90 ml) and concentrated in vacuo to leave a colourless oil. The resulting oil was purified by flash chromatography (0-10% EtOAc in petroleum ether (40:60) followed by 100% MeOH) to afford 2-bromo-4-fluoro-1-(methylsulfonyl)benzene as an orange oil (1.3 g, 81%). was added to the base solution were added reaction mixture stirred at 40° C. overnight The reaction mixture was concentrated in vacuo, EtOAc (10 ml) added washed with water (90 ml) concentrated in vacuo to leave a colourless oil The resulting oil was purified by flash chromatography (0-10% EtOAc in petroleum ether (40:60) followed by 100% MeOH)