反应详情

温度

75 °C

A solution of 2-pyridin-3-yl-pyrimidine-5-carboxylic acid (506 mg, 2.13 mmol), HCTU (970 mg, 2.34 mmol), and DIPEA (1 mL, 5.72 mmol) in DMF (10 mL) is stirred at rt under N2 for 10 min. 5-Fluoro-2-methyl-indol-1-ylamine (311 mg, 1.89 mmol) is added. The resulting mixture is stirred at 75° C. overnight. The mixture is cooled and portioned between EtOAc and water. The organic phase is separated, washed with saturated aqueous NaHCO3, water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 45% EtOAc in heptane to afford 2-pyridin-3-yl-pyrimidine-5-carboxylic acid (5-fluoro-2-methyl-indol-1-yl)-amide (300 mg, 46%) as a solid. MS: 348 (M+H). 1H NMR (300 MHz, DMSO-d6): δ 12.02 (s, 1H), 9.60 (d, 1H), 9.49 (s, 2H), 8.82-8.76 (m, 2H), 7.64 (dd, 1H), 7.39 (dd, 1H), 7.29 (dd, 1H), 6.94 (dt, 1H), 6.35 (s, 1H), 2.33 (s, 3H).

1. temperatureThe mixture is cooled
2. customThe organic phase is separated
3. washwashed with saturated aqueous NaHCO3, water and brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue is purified by silica gel chromatography
8. washeluting with 45% EtOAc in heptane