Potassium Phosphate, Tribasic → 1-(4-(2-Isopropyl-1-oxoisoindolin-5-yl)benzyl)-3-methylimidazolidine-2,4-dione

Participants

Reaction Steps

5-bromo-2-isopropylisoindolin-1-one (4A4) (0.418 mmol, 106 mg) was mixed with 3-methyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)imidazolidine-2,4-dione (4E1) (0.418 mmol, 138 mg), tricyclohexylphosphine (0.050 mmol, 14 mg), tris(dibenzylidineacetone) dipalladium chloroform adduct (0.021 mmol, 22 mg) and potassium phosphate (0.710 mmol, 151 mg) in dioxane (2 ml) and water (1 ml). The mixture was heated to 130° C. for 15 minutes in the microwave before addition of DCM (2 ml) and water (2 ml). The reaction was stirred vigorously for 30 minutes before collection of the organic layer using a hydrophobic fritted tube followed by concentration. Purification was achieved using basic HPLC and the desired fractions concentrated to give 1-(4-(2-isopropyl-1-oxoisoindolin-5-yl)benzyl)-3-methylimidazolidine-2,4-dione (Example 4a) 49.2 mg (31.2%); 1H NMR (400 MHz, CDCl3) δ 7.91 (d, 1H) 7.67-7.59 (m, 4H) 7.37 (d, 2H) 4.7 (sept, 1H) 4.62 (s, 2H) 4.4 (s, 2H) 3.79 (s, 2H) 3.07 (s, 3H) 1.31 (d, 6H) LCMS m/z (M+H) 378.2.

Provenance & Evidence