反应详情

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)+.

1. concentrationThe reaction mixture was then concentrated in vacuo
2. extractionThe product was extracted into DCM (2×3 mL)
3. washthe combined organics were washed with brine solution (2 ml)
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe crude product was purified by flash chromatography (Biotage, 5-12% methanol gradient in DCM)