Trimethylsilylacetylene → 2-Furan-2-yl-6-trimethylsilanylethynyl-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamine

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 6-bromo-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamine (500 mg, 1.78 mmol, see Examples 1 and 2 above) and (trimethylsilyl)acetylene (1.5 mL, 10 mmol) in a mixture of THF (10 mL) and TEA (5 mL) was added copper(I) iodide (68 mg, 0.36 mmol, 20 mol %) and PdCl2(PPh3)2 (190 mg, 0.27 mmol, 15 mol %). The reaction vessel was degassed and heated at 50° C. for 18 hours. After cooling to room temperature, the reaction mixture was diluted with water and extracted with methylene chloride. The combined organic extracts were dried over magnesium sulfate, and concentrated in vacuo to yield a crude product, which was purified by flash chromatography (silica gel, elution with 20% to 40% EtOAc/Hexane in volume) to afford the resulting 2-furan-2-yl-6-trimethylsilanylethynyl-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamine. The trimethylsilyl group was removed by treating a stirred solution of the crude material (2-furan-2-yl-6-trimethylsilanylethynyl-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamine) in wet MeOH (20 mL) with-Amberlyst A26 resin (2 g) for 1 hour. The suspension was filtered, and the resin was washed, sequentially with MeOH and THF. The filtrate was concentrated in vacuo to yield the desired 6-ethynyl-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamine (0.34 mg, 84% overall yield), which was used in the subsequent transformation without further purification.

Provenance & Evidence