反应详情

温度

110 °C

To a solution of DIPEA (1.38 mL, 7.9 mmol), 2-(6-cyano-2,3-difluorophenyl)malonic acid diethyl ester (1.35 g, 6.00 mmol), as prepared in the preceding step, and DMSO (1.7 mL) was added 2-(3-chlorophenyl)-2,2-difluoroethylamine (1.44 g, 7.51 mmol), as prepared in Example 2d. The reaction was stirred under argon at 110° C. for 69 h and then allowed to cool to room temperature. The mixture was diluted with saturated NaHCO3 (15 mL) and extracted with ether (2×15 mL). The combined organic layers were dried (Na2SO4) and concentrated. The residue was purified by flash chromatography on silica gel (3:1 hexane/EtOAc) to afford the title compound (1.525 g, 64%) as a tan crystalline solid. 1H NMR (300 MHz, CDCl3) δ 7.51-7.41 (m, 2H), 7.40-7.36 (m, 2H), 7.30 (dd, J=8.6 Hz, 1.3 Hz, 1H), 6.63 (t, J=8.2 Hz, 1H), 4.67 (br, 1H), 4.20 (q, J=7.0 Hz, 2H), 3.84 (d, J=2.0 Hz, 2H), 3.81 (dt, J=13.3 Hz, 6.9 Hz, 2H), 1.29 (t, J=7.1 Hz, 3H). LC/MS (ESI) calcd for C21H20ClF3N3O2 (MH+.MeCN) 438.1. found 438.2.

1. customas prepared in Example 2d
2. temperatureto cool to room temperature
3. extractionextracted with ether (2×15 mL)
4. dry with materialThe combined organic layers were dried (Na2SO4)
5. concentrationconcentrated
6. customThe residue was purified by flash chromatography on silica gel (3:1 hexane/EtOAc)