反应详情

温度

60 °C

To a solution of 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (0.5 g, 2.25 mmol) in THF (25 mL) is added carbonyl diimidazole (0.5 g, 2.7 mmol) and heated at 60° C. for 2 hours. The mixture is cooled to room temperature and (3-aminomethyl-benzyl)-carbamic acid tert-butyl ester (0.67 mL, 2.7 mmol) is added. The mixture is stirred for 12 h, diluted with EtOAc (100 mL), washed with brine (2×50 mL), dried with Na2SO4, filtered and concentrated in vacuo. The residue is purified by flash chromatography eluting with 20%-80% EtOAc/heptane to afford [3-({[2-(3-fluoro-phenyl)-pyrimidine-5-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester (0.8 g, 80%) as a solid. MS: 437 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 1.35 (s, 9H), 4.13 (d, J=6.1 Hz, 2H), 4.54 (d, J=5.9 Hz, 2H), 7.27-7.48 (m, 4H), 7.62 (m, 1H), 8.16 (m, 1H), 8.31 (m, 1H), 9.32 (s, 2H), 9.43 (m, 1H).

1. temperatureThe mixture is cooled to room temperature
2. washwashed with brine (2×50 mL)
3. dry with materialdried with Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue is purified by flash chromatography
7. washeluting with 20%-80% EtOAc/heptane