反应详情

HATU (365 mg, 0.96 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (99 mg, 0.32 mmol), 5-(acetylamino)-1H-indole-2-carboxylic acid (45 mg, 0.32 mmol) and diisopropylethylamine (167 uL, 0.96 mmol) in DMF (2 mL). The reaction mixture was stirred at RT overnight and was extracted with ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate and concentrated. The residue was purified by column chromatography (0-5% 2M NH3 solution of MeOH in DCM) and preparative TLC (5% 2M NH3 solution of MeOH in DCM) to afford the title compound (3.8 mg) as a white solid. 1H NMR (400 MHz, CDCl3-d) δ ppm 8.82 (s, 1H) 7.53 (s, 1H) 7.30-7.38 (m, 2H) 7.21-7.26 (m, 1H) 7.13 (s, 1H) 7.01 (s, 1H) 4.61 (d, J=6.41 Hz, 2H) 2.54 (s, 3H) 2.35 (s, 3H). LCMS: m/z 433 (M+1).

1. extractionwas extracted with ethyl acetate and water
2. washThe organic layer was washed with brine
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated
5. customThe residue was purified by column chromatography (0-5% 2M NH3 solution of MeOH in DCM) and preparative TLC (5% 2M NH3 solution of MeOH in DCM)