反应详情

温度

100 °C

In a 50 mL round-bottomed flask, 5-(4-isopropylpiperazin-1-yl)pyridin-2-amine (200 mg, 908 μl mmol, Eq: 1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (243 mg, 1.09 mmol, Eq: 1.2) and cesium carbonate (887 mg, 2.72 mmol, Eq: 3) were combined with dioxane (20 ml) to give a orange suspension. 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (78.8 mg, 136 mmol, eq: 0.15) was added. Tris(dibenzylideneacetone)dipalladium(0) (41.6 mg, 45.4 μmol, Eq: 0.05) was added. The solution was degassed with Ar for 10 min. The solution was heated at 95-105° C. for 48 h. The solution was diluted with 200 ml DCM. MgSO4 was added and the suspension stirred for 10 min. The solid was filtered and washed several times with DCM. The organics were concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 50% to 100% EtOAc/hexanes gradient) to give 6-chloro-4-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one (273 mg, 83%). LC/MS-ESI observed [M+H]+ 363.

1. customto give a orange suspension
2. customThe solution was degassed with Ar for 10 min
3. additionThe solution was diluted with 200 ml DCM
4. additionMgSO4 was added
5. filtrationThe solid was filtered
6. washwashed several times with DCM
7. concentrationThe organics were concentrated in vacuo
8. customThe crude material was purified by flash chromatography (silica gel, 40 g, 50% to 100% EtOAc/hexanes gradient)