反应详情

1-(4-bromobenzyl)-5,5-dimethylimidazolidine-2,4-dione (8B4) (0.168 mmol, 50 mg) (prepared according to the method described for intermediate (1B4), 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (1A5) (0.1 mmol, 53.0 mg), tris(dibenzylidineacetone)dipalladium (0.008 mmol, 8.1 mg), tricyclohexylphosphine (0.02 mmol, 5.7 mg) and potassium phosphate (0.27 mmol, 60.7 mg) were suspended in dioxane (3 ml) and water (1 ml) and heated to 130° C. in the microwave for 15 min. The reaction mixture was quenched with water (6 ml) and DCM (9 ml) and the organic layer separated using a hydrophobic fritted tube. The organic phase was concentrated and the residue purified on silica eluting with 0-100% EtOAc/heptane to give 1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-5,5-dimethylimidazolidine-2,4-dione (8I1) 21.3 mg (53%); 1H NMR (400 MHz, CDCl3) δ 7.88 (d, 1H) 7.54 (d, 1H) 7.57 (m, 3H) 7.43 (d, 2H) 7.33 (bs, 1H) 4.56 (s, 2H) 4.37 (s, 2H) 3.94 (m, 1H) 1.34 (s, 6H) 0.95-0.88 (m, 4H).

1. customThe reaction mixture was quenched with water (6 ml) and DCM (9 ml)
2. customthe organic layer separated
3. concentrationThe organic phase was concentrated
4. customthe residue purified on silica eluting with 0-100% EtOAc/heptane