反应详情

A solution of 2-pyridin-3-yl-pyrimidine-5-carboxylic acid (664 mg, 2.79 mmol), HCTU (1.27 g, 3.07 mmol), and DIPEA (1.4 mL, 8.02 mmol) in DMF (15 mL) is stirred at rt under N2 for 10 min. 5-fluoro-3-methyl-indol-1-ylamine (491 mg, 2.55 mmol) is added. The resulting mixture is stirred at rt overnight. The mixture is 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 triturated in ether (3 times) and methanol to afford 2-pyridin-3-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide (375 mg, 42%) as a solid. MS: 348 (M+H). 1H NMR (300 MHz, DMSO-d6): δ 12.10 (s, 1H), 9.61-9.60 (m, 1H), 9.45 (s, 2H), 8.81-8.80 (m, 1H), 8.77 (dt, 1H), 7.64 (dd, 1H), 7.41 (dd, 1H), 7.35 (dd, 1H), 7.32 (s, 1H), 7.03 (td, 1H), 2.27 (s, 3H). IC50=10 nM.

1. customThe organic phase is separated
2. washwashed with saturated aqueous NaHCO3, water and brine
3. dry with materialdried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue is triturated in ether (3 times)