2-Amino-3,5-dibromopyrazine → 5-bromo-3-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyrazin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a round bottom flask was added 4-ethynyl-1-methyl-1H-pyrazole (8.5 g, 80 mmol, Preparation #Q.1), 3,5-dibromopyrazin-2-amine (16.8 g, 66.4 mmol), THF (166 mL), PdCl2(PPh3)2 (2.33 g, 3.32 mmol), copper(I) iodide (0.633 g, 3.32 mmol) and TEA (27.8 mL, 199 mmol). The mixture was heated to about 70° C. for about 1 h. The mixture was cooled to rt. The solids were filtered away and rinsed with THF (50 mL). The filtrate was partitioned with water (300 mL) and the mixture was extracted with EtOAc (400 mL). The organic layer was dried with anhydrous MgSO4, filtered and concentrated in vacuo. The residue was triturated with EtOH (100 mL) and the solid material was collected by filtration. The mother liquor was purified by flash chromatography (300 g silica gel column, heptane/EtOAc 10:1 to 0:1) to give 5-bromo-3-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyrazin-2-amine (15.2 g, 82%): LC/MS (Table 2, Method c) Rt=1.40 min; MS m/z 278 (M+H)+.

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