Tetrabutylammonium Fluoride → 4-[1-(2-aminopyrimidin-4-yl)-3-(2-hydroxypropan-2-yl)-1H-indazol-6-yl]-2-(1-methyl-1H-pyrazol-3-yl)but-3-yn-2-ol

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-[1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]propan-2-ol (135 mg, 0.31 mmol) in dry THF (4 mL) under an atmosphere of nitrogen was introduced bis(triphenylphosphine)palladium(II) chloride (21.6 mg, 0.03 mmol), TBAF (0.37 mL of a 1M solution in THF, 0.37 mmol) and 2-(1-methyl-1H-pyrazol-3-yl)-4-(trimethylsilyl)but-3-yn-2-ol (137 mg, 0.62 mmol). The reaction mixture was warmed to 50° C. for 1.5 hr. After cooling to RT, the reaction mixture was diluted with saturated aqueous sodium bicarbonate solution (4 ml) and extracted with EtOAc (2×10 mL extractions). The combined extracts were washed with water (5×5 mL), brine (5 mL), dried (Na2SO4) and filtered. After concentration of the filtrate in vacuo, the residue was purified by silica gel flash column chromatography (DCM containing a 1-10% methanol gradient) to furnish the title compound as an off-white solid: 1H NMR (DMSO, 500 MHz) delta 1.63 (6H, s), 1.83 (3H, s), 3.82 (3H, s), 5.57 (1H, s), 6.02 (1H, s), 6.36 (1H, d, J=2.1 Hz), 6.99 (2H, s), 7.05 (1H, d, J=5.5 Hz), 7.31 (1H, d, J=8.4 Hz), 7.61 (1H, d, J=2.0 Hz), 8.11 (1H, d, J=8.3 Hz), 8.27 (1H, d, J=5.5 Hz), 8.84 (1H, s); LC-MS: m/z=+418.10 (M+H)+.

Provenance & Evidence