反应详情

温度

60 °C

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5-fluoro-indol-1-yl)-amide (300 mg, 0.824 mmol) in MeCN (20 mL) is treated with NCS (185 mg, 1.42 mmol) and the mixture is stirred at 60° C. in a sealed flask for 2 h. The mixture is then concentrated, diluted with 10% aqueous Na2S2O8 (20 mL), and extracted with EtOAc (3×20 mL). The combined organic layer is separated, dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10%-20% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylicacid(3 chloro-5-fluoro-indol-1-yl)-amide (160 mg, 49%). MS: 399 (M+H); 1H NMR (300 MHz, CDCl3): δ 8.79 (s, 1H), 8.04 (d, 1H), 7.92 (d, 1H), 7.18 (m, 1H), 7.04 (s, 1H), 7.00 (m, 3), 6.76 (m, 1), 2.52 (s, 3H).

1. concentrationThe mixture is then concentrated
2. additiondiluted with 10% aqueous Na2S2O8 (20 mL)
3. extractionextracted with EtOAc (3×20 mL)
4. customThe combined organic layer is separated
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue is purified by silica gel chromatography
9. washeluting with 10%-20% EtOAc in heptane