反应详情

A solution 5-(5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-isophthalonitrile (0.016 g, 0.0535 mmol), methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl ester (0.017 g, 0.0535 mmol), lithium iodide (0.0036 g, 0.0268 mmol) and potassium carbonate (0.0074 g, 0.0535 mmol) in DMF (0.5 mL) was stirred at 0° C. for 4 h, then warmed to rt overnight. Reaction mixture was diluted with ethyl acetate, washed with water (2×), dried (MgSO4) and concentrated. The resulting residue was purified by flash column chromatography (silica gel, 10 to 50% ethyl acetate/hexane), then by reverse phase HPLC (Phenomenex Synergi® column, 5 to 100% acetonitrile/H2O) to give an yellow solid (0.0091 g, 31%). 1H NMR (300 MHz, CD3OD): δ 8.31 (s, 2H), 8.13 (s, 1H), 7.25 (d, J=8.7 Hz, 2H), 6.86 (d, J=8.4 Hz, 2H), 5.79 (s, 1H), 5.74 (s, 1H), 5.17 (d, J=16.8 Hz, 1H), 4.20 (s, 2H), 4.13 (d, J=16.8 Hz, 1H), 3.75 (s, 3H), 2.2-2.0 (m, 1H), 1.12 (d, J=6.6 Hz, 3H), 1.07 (d, J=6.6 Hz, 3H). Mass spectrum: 553.1 (M+H)+.

1. customReaction mixture
2. washwashed with water (2×)
3. dry with materialdried (MgSO4)
4. concentrationconcentrated
5. customThe resulting residue was purified by flash column chromatography (silica gel, 10 to 50% ethyl acetate/hexane)