Potassium Phosphate, Tribasic → 1-{4-[1-(cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yl]benzyl}-3-methylimidazolidine-2,4-dione

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Reaction Steps

1-(Cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yltrifluoromethanesulfonate [(Example 1, Step 9), 30 mg, 0.077 mmol], 3-methyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]imidazolidine-2,4-dione (38.2 mg, 0.116 mmol, 1.5 equiv), potassium phosphate (49.1 mg, 0.231 mmol, 3 equiv) and palladium tetrakis(triphenylphosphine) (8.91 mg, 0.007 mmol, 0.1 equiv) were combined in dioxane (2 mL) and water (0.2 mL) and heated at 90° C. for 1 hour. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (15 mL, saturated aqueous) and extracted with ethyl acetate (2×25 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC (80:20 to 5:95; water with 0.05% trifluoroacetic acid:acetonitrile with 0.05% trifluoroacetic acid) to afford the titled compound: 1H NMR (400 MHz, CDCl3) δ 7.69 (1H, d, J=8.5 Hz), 7.34 (1H, d, J=8.5 Hz), 7.28 (4H, dd, J=8.8, 8.1 Hz), 4.58 (2H, s), 4.52 (2H, d, J=7.1 Hz), 3.74 (2H, s), 3.01 (3H, s), 1.40-1.32 (1H, m), 0.65-0.60 (2H, m), 0.48-0.44 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 444.1652 [(M+H)+; calculated for C22H21F3N5O2: 444.1642].

Provenance & Evidence