Lithium diisopropylamide → 4-[1-(2-Aminopyrimidin-4-yl)-3-methylindazol-6-yl]-2-[1-(triphenylmethyl)imidazol-4-yl]but-3-yn-2-ol

Participants

Reaction Steps

To a solution of 4-(6-ethynyl-3-methylindazol-1-yl)pyrimidin-2-amine (180 mg at 90% purity, 0.65 mmol) in THF (2.5 mL) at −78° C. under nitrogen was added 2M LDA in THF (0.81 mL, 1.63 mmol). After 5 minutes 1-[1-(triphenylmethyl)imidazol-4-yl]ethanone (458.08 mg, 1.3 mmol) in THF (1.5 mL) was added. After 20 minutes, the mixture was allowed to warm up to RT and stirred for a further 1 hr. The reaction mixture was quenched by addition of saturated aqueous NH4Cl (1 mL). The volatiles were removed in vacuo and the mixture was diluted with DCM (10 ml) and washed with water (2 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography (Biotage, 2-12% methanol gradient in DCM) to give the title intermediate as a yellow oil: 1H NMR (500 MHz, CDCl3) delta 1.96 (3H, s), 2.58 (3H, s), 4.41 (1H, s), 5.36 (2H, s), 6.96 (1H, d, J=1.0), 7.19-7.09 (6H, m), 7.24 (1H, d, J=5.7 Hz), 7.35-7.30 (10H, m), 7.44 (1H, d, J=1.0 Hz), 7.53 (1H, d, J=8.2), 8.24 (1H, d, J=5.7), 8.83 (1H, s); LC-MS: m/z=+360.35 (M-C(C6H5)3)+.

Provenance & Evidence