Cesium carbonate → 1-({5-[1-(cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yl]-6-fluoropyridin-2-yl}methyl)-3-methylimidazolidine-2,4-dione

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Reaction Steps

{5-[1-(Cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yl]-6-fluoropyridin-2-yl}methyl methanesulfonate (25 mg, 0.056 mmol) was dissolved in acetonitrile (0.56 mL) and treated with 3-methylimidazolidine-2,4-dione (9.6 mg, 0.084 mmol), cesium carbonate (55 mg, 0.17 mmol) and tetra-n-butylammonium iodide (4.2 mg, 0.011 mmol). The mixture was placed into a preheated oil bath at 85° C. for 30 minutes. The mixture was cooled to ambient temperature, diluted with ethyl acetate and washed with sodium bicarbonate (2×5 mL, aqueous saturated). The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative reverse phase HPLC (85:15 to 36:64; water with 0.05% trifluoroacetic acid:acetonitrile with 0.05% trifluoroacetic acid) to afford the titled compound as a white solid. H1-NMR (400 MHz, CDCl3): δ 7.84 (1H, d, J=8.5 Hz), 7.77 (1H, dd, J=9.2, 7.6 Hz), 7.39 (1H, d, J=8.6 Hz), 7.30 (1H, dd, J=7.5, 1.5 Hz), 4.77 (1H, d, J=16.4 Hz), 4.67 (1H, d, J=16.2 Hz), 4.61 (2H, d, J=7.1 Hz), 4.16 (1H, d, J=17.4 Hz), 4.07 (1H, d, J=17.1 Hz), 3.32 (3H, s), 1.49-1.39 (1H, m), 0.78-0.66 (2H, m), 0.61-0.11 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 463.1514 [(M+H)+; calculated for C21H19F4N6O2: 463.1500].

Provenance & Evidence