4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)but-3-yn-2-ol → 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1H-imidazol-2-yl)but-3-yn-2-ol

Participants

Reaction Steps

A solution of 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)but-3-yn-2-ol in 4M HCl in dioxane (2.5 ml) was stirred at 40° C. for 2 h and then at 50° C. for a further 1 hr. The reaction mixture was then concentrated in vacuo and basified using saturated aqueous sodium bicarbonate solution. The product was extracted into DCM (2×3 mL) and the combined organics were washed with brine solution (2 ml), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography (Biotage, 5-12% methanol gradient in DCM) to give the title compound as an off-white solid: 1H NMR (500 MHz, DMSO) delta 1.90 (3H, s), 2.57 (3H, s), 6.42 (1H, s), 6.83 (1H, s), 6.96 (2H, s), 7.10-6.99 (2H, m), 7.35 (1H, d, J=8.2 Hz), 7.84 (1H, d, J=8.2 Hz), 8.25 (1H, d, J=5.5 Hz), 8.86 (1H, s), 12.01 (1H, s); LC-MS: m/z=+360.05 (M+H)+.

Provenance & Evidence