反应详情

温度

80 °C

A solution of 2-(3-fluorophenyl)-pyrimidine-5-carboxylic acid (0.33 g), HATU (0.67 g) and hydroxyazabenzotriazole (0.26 g) in dry DMF (15 mL) is stirred at rt for 30 min under N2. A solution of 1-amino-4-fluoroindole (0.24 g) in dry DMF (5 mL) is added followed by the addition of DIPEA (0.39 mL). The mixture is stirred at 80° C. for 24 h, cooled to rt, and then concentrated in vacuo. The residue is dissolved in EtOAc and washed with water, brine and dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 60% DCM/heptane to afford 2-(3-fluorophenyl)pyrimidine-5-carboxylic acid-(4-fluoroindol-1-yl)amide (0.24 g, 53%) as a solid. MS: 351 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 6.64 (d, 1H), 6.89-6.92 (q, 1H), 7.15-7.22 (m, 1H), 7.31-7.33 (d, 1H), 7.46-7.52 (m, 1H), 7.56 (d, 1H), 7.63-7.70 (q, 1H), 8.18-8.23 (d, 1H), 8.34-8.37 (d, 1H), 9.45 (s, 2H), 12.30 (s, 1H). IC50=11 nM.

1. temperaturecooled to rt
2. concentrationconcentrated in vacuo
3. dissolutionThe residue is dissolved in EtOAc
4. washwashed with water, brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue is purified by silica gel chromatography
9. washeluting with 60% DCM/heptane