反应详情

温度

130 °C

2-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (1A5) (3.34 mmol, 1.0 g), 1-(4-bromobenzyI)-3-methylimidazolidine-2,4-dione (1B6) (3.34 mmol, 0.946 g), tris(dibenzylidineacetone)dipalladium (0.167 mmol, 153 mg), tricyclohexylphosphine (0.401 mmol, 112 mg) and potassium phosphate (5.68 mmol, 1.2 mg) were suspended in a mixture of dioxane (10 ml) and water (5 ml) and heated at 130° C. in the microwave for 15 min. The reaction was quenched with sat. NaHCO3 and diluted with DCM and then passed through a hydrophobic fritted tube. The combined organic layers were concentrated and the residue purified on silica eluting with 75-100% EtOAc/Heptane to afford 1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-3-methylimidazolidine-2,4-dione (Example 1a) (685 mg, 55%) 1H NMR (400 MHz, CDCl3) δ 7.99 (d, 1H) 7.65 (d, 1H) 7.62 (d, 2H) 7.59 (s, 1H) 7.36 (d, 2H) 4.63 (s, 2H) 4.38 (s, 2H) 3.79 (s, 2H) 3.08 (s, 3H) 2.95 (m, 1H) 0.98-0.87 (m, 4H) LCMS m/z (M+H) 376.2.

1. customThe reaction was quenched with sat. NaHCO3
2. additiondiluted with DCM
3. custompassed through a hydrophobic fritted tube
4. concentrationThe combined organic layers were concentrated
5. customthe residue purified on silica eluting with 75-100% EtOAc/Heptane