反应详情

温度

0 °C

To a solution of tert-butyl(1-(4-(5-oxo-3-phenyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)phenyl)cyclobutyl)carbamate (31 mg, 0.07 mmol) in dry DMF (1 mL) was added sodium hydride (3 mg, 0.07 mmol) at 0° C. under nitrogen. After 1 h at 0° C., 2-bromoacetonitrile (14 μL, 0.20 mmol) was added and the resulting mixture was stirred for an additional 30 min at 0° C. A saturated solution of NH4Cl was added and the mixture was extracted with dichloromethane (3×) using a phase separator (Isolute® SPE). The combined organic phases were concentrated to dryness under reduced pressure. The resulting residue was purified by silica gel chromatography (gradient 0 to 40% EtOAc in hexane) to give the title compound (10 mg, 29%). 1H NMR (500 MHz, CDCl3): 8.36 (1H, s), 7.35 (2H,d), 7.30 (2H, d), 7.27-7.26 (3H, m), 7120-7.18 (2H, m), 5.05 (1H, br s), 4.59 (2H, s), 3.86 (2H, t), 3.40 (2H, t), 2.55-2.25 (4H, m), 2.10-2.02 (1H, m), 1.85-1.76 (1H, m), 1.44-1.18 (9H, br).

1. extractionthe mixture was extracted with dichloromethane (3×)
2. concentrationThe combined organic phases were concentrated to dryness under reduced pressure
3. customThe resulting residue was purified by silica gel chromatography (gradient 0 to 40% EtOAc in hexane)