Triethylamine → N-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-2-methoxy-2-methyl-propionamide

Participants

Reaction Conditions

Reaction Steps

2-Methoxy-2-methyl-N-(5-trimethylsilanylethynyl-pyridin-2-yl)-propionamide (Example 13, step 2) (90 mg, 0.31 mmol) was dissolved in THF (8 ml). 1-Fluoro-3-iodobenzene (83 mg, 0.37 mmol, 1.2 equiv.), Et3N (130 μl, 0.93 mmol, 3 equiv.), bis-(triphenylphosphine)-palladium(II)dichloride (11 mg, 15 μmol, 0.05 equiv.) and copper(I)iodide (1.8 mg, 10 μmol, 0.03 equiv.) were added under nitrogen and the mixture was heated to 70° C. TBAF 1M in THF (370 μl, 0.37 mmol, 1.2 equiv.) was added dropwise at 70° C. The reaction mixture was stirred for 1 hour at 70° C., filtered through celite and the filtrate evaporated to dryness. The crude product was purified by flash chromatography with a silica gel column eluting with heptane:ethyl acetate 100:0->90:10. The desired N-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-2-methoxy-2-methyl-propionamide (64 mg, 66% yield) was obtained as a yellow oil, MS: m/e=313.0 (M+H+).

Provenance & Evidence