Cesium carbonate → 7-(2-Fluorophenyl)-4-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-(thien-3-yl)pyrazolo[1,5-d][1,2,4]triazine

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-bromo-7-(2-fluorophenyl)-4-methyl-2-(2-methyl-2H-[1,2,4]triazol-3ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (100.7 mg, 0.241 mmol), thiophene-3-boronic acid (46.8 mg, 0.366 mmol) and cesium carbonate (157.0 mg, 0.482 mmol) in anhydrous 1,4-dioxane (10 ml) was degassed by three freeze-pump-thaw cycles. Then tris(dibenzylideneacetone)dipalladium(0) (22.5 mg, 0.0246 mmol) and a 0.1M solution of tri-tert-butylphosphine in 1,4-dioxane (0.58 ml, 0.058 mmol) was added and two more freeze-pump-thaw cycles were performed. The mixture was heated at 90° C. under nitrogen for 22 h, then filtered through glass fibre paper. The solid was washed with ethyl acetate, and the filtrates were washed with saturated aqueous NaCl (15 ml). The aqueous layer was further extracted with ethyl acetate (25 ml), and the combined extracts were dried (NaSO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 2% MeOH/CH2Cl2) to give 83.8 mg (83%) of the title compound as an orange solid: mp=124-129° C. (CH2Cl2-EtOAc-isohexane); 1H NMR (360 MHz, CDCl3) δ 2.60 (3H, s), 3.71 (5H, s), 5.46 (2H, s), 7.18 (1H, d, J=4.9 Hz), 7.27 (1H, m), 7.38 (1H, m), 7.38 (1H, s), 7.44 (1H, dd, J=4.9, 3.0 Hz), 7.63 (1H, m), 7.75 (1H, t, J=7.1 Hz), 7.83 (1H, s); MS (ES+) m/e 422 [M+H]+. Anal. Found C, 56.94; H, 4.04; N, 22.49%. C20H16FN7OS.0.08 C4H8O2 requires C, 56.96; H, 3.91; N, 22.88%.

Provenance & Evidence