反应详情

温度

120 °C

500 mg (1.62 mmol) of the compound from Example 4A, 178 mg (1.78 mmol) of N-methylpiperazine, 58 mg (0.12 mmol) of dicyclohexyl-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine, 22 mg (24 μmol) of tris(dibenzylideneacetone)dipalladium and 1.32 g (4.05 mmol) of cesium carbonate are combined. The mixture is degassed and vented twice with argon, 12.5 ml of a mixture of tert-butanol and toluene (1:5) are added, the mixture is again degassed and vented twice with argon and heated at 120° C. for 24 h. Another 58 mg (0.12 mmol) of dicyclohexyl-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine and 22 mg (24 μmol) of tris(dibenzylideneacetone)dipalladium are then added, the mixture is heated at 120° C. overnight, another 324 mg (3.24 mmol) of N-methylpiperazine are then added and the mixture is heated at 120° C. for a further night. After cooling, the reaction mixture is filtered through kieselguhr, the filtrate is concentrated and the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid).

1. customThe mixture is degassed
2. additionare added
3. customthe mixture is again degassed
4. temperaturethe mixture is heated at 120° C. overnight
5. temperaturethe mixture is heated at 120° C. for a further night
6. temperatureAfter cooling
7. filtrationthe reaction mixture is filtered through kieselguhr
8. concentrationthe filtrate is concentrated
9. customthe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid)