反应详情

温度

140 °C

A mixture of tris(dibenzylideneacetone)dipalladium (0) (18 mg, 0.020 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (23 mg, 0.040 mmol) in toluene (1 mL) and DMF (1 mL) was degassed under a stream of nitrogen gas with stirring for 15 minutes. 5-(8-Bromoisoquinolin-3-ylamino)pyrazine-2-carbonitrile (65 mg, 0.20 mmol), benzophenone imine (36 mg, 0.20 mmol) and caesium carbonate (130 mg, 0.40 mmol) were added and the mixture was degassed for a further 5 minutes, then heated at 140° C. for 40 minutes in a microwave reactor. Upon cooling the reaction mixture was diluted with ethyl acetate and filtered through celite, washed sequentially with water and brine then dried (Na2SO4) and concentrated to dryness to afford a brown oil. The residue was dissolved in THF (2 mL) and treated with aqueous hydrogen chloride (2 mL, 2M) for 30 minutes and then concentrated to dryness. Preparative HPLC gave the title compound (5.64 mg, 0.022 mmol, 11%). 1H NMR (d6-DMSO, 400 MHz) δ 10.90 (br s, 1H), 9.35 (s, 1H), 8.80 (s, 1H), 8.70 (s, 1H), 8.25 (s, 1H), 7.40 (t, 1H, J=7.8, 6.8 Hz), 6.95 (d, 1H, J=7.8 Hz), 6.60 (d, 1H, J=6.8 Hz), 6.25 (s, 1H). LC-MS (2) Rt=2.32 min; m/z (ESI+) 263 (M+H).

1. customwas degassed under a stream of nitrogen gas
2. customthe mixture was degassed for a further 5 minutes
3. temperatureUpon cooling the reaction mixture
4. additionwas diluted with ethyl acetate
5. filtrationfiltered through celite
6. washwashed sequentially with water and brine
7. dry with materialthen dried (Na2SO4)
8. concentrationconcentrated to dryness
9. customto afford a brown oil
10. concentrationconcentrated to dryness