反应详情

A solution of 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (810 mg, 3.76 mmol), PyBrOP (1.76 g, 3.78 mmol), and DIPEA (1.9 mL, 10.89 mmol) in DMF (15 mL) is stirred at rt under N2 for 10 min. 5-Fluoro-2-methyl-indol-1-ylamine (560 mg, 3.41 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 purified by silica gel chromatography eluting with 3% MeOH in DCM to afford 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-2-methyl-indol-1-yl)-amide (174 mg, 14%) as a solid. MS: 362 (M+H). 1H NMR (300 MHz, DMSO-d6): δ 11.82 (s, 1H), 9.30 (d, 1H), 8.81 (d, 1H), 8.46 (d, 1H), 8.03 (dt, 1H), 7.59 (dd, 1H), 7.43 (dd, 1H), 7.29 (dd, 1H), 6.98 (dt, 1H), 6.35 (s, 1H), 2.79 (s, 3H), 2.38 (s, 3H). IC50=8 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 purified by silica gel chromatography
7. washeluting with 3% MeOH in DCM