反应详情

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (340 mg, 1.46 mmol, prepared according to the general procedure described in Example 1, steps 3 and 4), HOAt (248 mg, 1.82 mmol), and HATU (645 mg, 1.70 mmol) in DMF (15 mL) is stirred at rt under N2 for 20 min. 5-Fluoro-2-methyl-indol-1-ylamine (237 mg, 1.44 mmol) and DIPEA (380 μL, 2.18 mmol) are added. The resulting mixture is stirred at 80° 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 20% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5-fluoro-2-methyl-indol-1-yl)amide (300 mg, 55%) as a solid. MS: 379 (M+H). 1H NMR (300 MHz, CD3OD): δ 9.14 (s, 1H), 8.38-8.20 (m, 3H), 7.56-7.52 (m, 1H), 7.30-7.27 (m, 2H), 7.19-7.16 (m, 1H), 6.96-6.90 (m, 1H), 6.32 (s, 1H), 2.83 (s, 3H), 2.42 (s, 3H).

1. stirringThe resulting mixture is stirred at 80° C. overnight
2. temperatureThe mixture is cooled
3. customThe organic phase is separated
4. washwashed with saturated aqueous NaHCO3, water and brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue is purified by silica gel chromatography
9. washeluting with 20% EtOAc in heptane