Trimethylsilylacetylene → 5-Bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 3,5-dibromopyrazin-2-amine (40.0 g, 158 mmol), TEA (66.1 mL, 475 mmol), and copper(I) iodide (0.301 g, 1.58 mmol) in THF (1172 ml) was added PdCl2(PPh3)2 (1.11 g, 1.58 mmol). The reaction mixture was cooled at about 0° C. and a solution of (trimethylsilyl)acetylene (20.8 mL, 150 mmol) in THF (146 mL) was added drop-wise. The reaction mixture was stirred at about 0-10° C. for about 7 h and then concentrated under reduced pressure. The dark brown residue was dissolved in DCM (600 mL) and filtered through a Celite® pad (3 cm in height×9 cm in diameter) while eluting with DCM (300 mL). The filtrate was washed with water (2×500 mL) and brine (500 mL), dried over anhydrous MgSO4, filtered through a Florisil® pad (1 cm in height by 9 cm in diameter) while washing with DCM/MeOH (9:1, 200 mL), and concentrated under reduced pressure to give a brown solid. The solid was triturated and sonicated with warm petroleum ether (b.p. 30-60° C., 250 mL), cooled and collected, washing with petroleum ether (b.p. 30-60° C.; 2×100 mL), and dried in a vacuum oven at about 70° C. to give 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (34.6 g, 70%): LC/MS (Table 2, Method d) Rt=1.59 min; MS m/z: 272 (M+H)+.

Provenance & Evidence