反应详情

温度

50 °C

A solution of 2-(2-pyridyl)-4-methyl-pyrimidine-5-carboxylic acid (516 mg, 4 mmol) and 4-(1-amino-5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol (566 mg, 4 mmol) in DMF (5 mL) is stirred at 50° C. for 1 h. The mixture is treated with DMTMM (662 mg, 4 mmol) and stirred at 50° C. for 1 h. The mixture is diluted with saturated aqueous Na2CO3 (50 mL), and extracted with EtOAc (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 4%-10% MeOH in DCM to afford 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid [5-fluoro-3-(3-hydroxy-3-methyl-butyl)-indol-1-yl]-amide (450 mg, 44%). MS: 434 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 9.25 (s, 1H), 8.81 (d, 1H), 8.47 (d, 1H), 8.02 (m, 1H), 7.58 (m, 1H), 7.43 (m, 3H), 7.06 (m, 1H), 4.29 (s, OH, 1H), 2.78 (s, 3H), 2.72 (m, 2H), 1.77 (m, 2H), 120 (s, 6H).

1. extractionextracted with EtOAc (3×50 mL)
2. dry with materialThe combined organic layer is dried (Na2SO4)
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe residue is purified by silica gel chromatography
6. washeluting with 4%-10% MeOH in DCM