反应详情

To intermediate 38 (0.40 g, 0.98 mmol) in dry DMF (20 mL) was added 3-(4-fluorophenylamino)-3-oxopropanoic acid (47) (0.39 g, 2.0 mmol) [US 2007/0004675 A1], and EDC.HCl (0.38 g, 2.0 mmol) and the mixture was stirred at r.t. for 2 h. The mixture was then partitioned between ethyl acetate and water resulting in precipitate. The precipitate was isolated by suction filtration and combined with the organic phase from the filtrate, concentrated, and dried in vacuum. The residue was dissolved in acetone (50 mL) to give a colorless solution. The solution was diluted with water (20 mL) and TFA (2 mL), heated to reflux for 3 h, then cooled and concentrated. The precipitated product was isolated by suction filtration, and dried in vacuum to afford intermediate 48 (0.35 g, 66%, presumably as the trifluoroacetate salt). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.59 (s, 1H), 10.29 (s, 1H), 10.14 (s, 1H), 9.15 (s, 1H), 8.59 (s, 1H), 8.58 (m, 1H), 8.52 (d, J=8.2 Hz, 1H), 8.39 (dd, J=8.2, 2.0 Hz, 1H), 7.90 (dd, J=13.1, 2.2 Hz, 1H), 7.65-7.60 (m, 2H), 7.54-7.44 (m, 2H), 7.17 (t, J=8.8 Hz, 2H), 6.75 (d, J=5.5 Hz, 1H), ˜3.50 (s, 2H, obscured by water peak). MS (m/z): 545.2 (M+H).

1. customThe mixture was then partitioned between ethyl acetate and water resulting in precipitate
2. customThe precipitate was isolated by suction filtration
3. concentrationconcentrated
4. customdried in vacuum
5. dissolutionThe residue was dissolved in acetone (50 mL)
6. customto give a colorless solution
7. temperatureheated
8. temperatureto reflux for 3 h
9. temperaturecooled
10. concentrationconcentrated
11. customThe precipitated product was isolated by suction filtration
12. customdried in vacuum