反应详情

To a solution of 1-(2-aminopyrimidin-4-yl)-6-ethynyl-N,N-dimethylindazole-3-carboxamide (80 mg, 0.217 mmol) in THF (1.0 mL) at −78° C. under nitrogen was added 2M LDA in THF (0.27 mL, 0.54 mmol). After 5 minutes 1-pyrimidin-2-yl-ethanone (79 mg, 0.65 mmol) in THF (0.5 mL) was added and the reaction was allowed to warm to RT after 20 minutes. After a further 30 minutes the reaction mixture was quenched by addition of saturated aqueous NH4Cl (0.5 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, 0-2% methanol in DCM). Trituration of the partially purified product from EtOAc-heptane gave the title compound: 1H NMR (250 MHz, MeOD) delta 1.93-2.02 (3H, m), 3.22 (3H, s), 3.41 (3H, s), 7.24 (1H, d, J=5.79 Hz), 7.40-7.55 (2H, m), 7.97 (1H, d, J=8.38 Hz), 8.29 (1H, d, J=5.79 Hz), 8.88 (2H, d, J=5.03 Hz), 9.12 (1H, s); LC-MS: m/z=+429.45 (M+H)+.

1. customAfter a further 30 minutes the reaction mixture was quenched by addition of saturated aqueous NH4Cl (0.5 mL)
2. customThe volatiles were removed in vacuo
3. additionthe mixture was diluted with DCM (10 ml)
4. washwashed with water (2 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude product was purified by flash chromatography (Biotage, 0-2% methanol in DCM)