Tetrahydrofuran → 2-Tert-butyl-6-(2,5-difluoro-phenylethynyl)-[1,2,4]triazolo[1,5-a]pyrimidine

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Reaction Conditions

Reaction Steps

2-tert-Butyl-6-trimethylsilanylethynyl-[1,2,4]triazolo[1,5-a]pyrimidine (example 43, step 1) (100 mg, 0.37 mmol) was dissolved in DMF (1 ml). 1,4-Difluoro-2-iodobenzene (176 mg, 0.73 mmol, 2 equiv.), Et3N (150 μl, 1.1 mmol, 3 equiv.), Bis-(triphenylphosphine)-palladium (II) dichloride (13 mg, 0.02 mmol, 0.05 equiv.), triphenylphosphine (3 mg, 0.011 mmol, 0.03 equiv.) and copper (I) iodide (2 mg, 0.011, 0.03 equiv.) were added under nitrogen and the mixture was heated to 80° C. TBAF 1M in THF (440 μl, 0.44 mmol, 1.2 equiv.) was added dropwise in 20 minutes at 80° C. The reaction mixture was stirred for 5 minutes at 80° C. The reaction mixture was evaporated and extracted with saturated NaHCO3 solution and two times with a small volume of dichloromethane. The crude product was purified by flash chromatography by directly loading the dichloromethane layers onto a 20 g silica gel column and eluting with heptane:ethyl acetate 100:0->50:50. The desired 2-tert-butyl-6-(2,5-difluoro-phenylethynyl)-[1,2,4]triazolo[1,5-a]pyrimidine (73 mg, 64% yield) was obtained as a light yellow solid, MS: m/e=313.1 (M+H+).

Provenance & Evidence