反应详情

温度

60 °C

To a solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (0.195 g, 0.89 mmol) in THF (5 mL) is added carbonyl diimidazole (0.18 g, 1.1 mmol) and heated at 60° C. for 2 hours. The mixture is cooled to room temperature. (3-Aminomethyl-benzyl)-carbamic acid tert-butyl ester (0.25 mL, 1.1 mmol) is added and the mixture is stirred for 12 hours. The mixture is 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)-4-methyl-pyrimidine-5-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester (0.32 g, 80%) as a solid. MS: 451 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 1.38 (s, 9H), 2.65 (s, 3H), 4.14 (d, J=6.1 Hz, 2H), 4.50 (d, J=5.6 Hz, 2H), 7.15 (m, 1H), 7.24 (m, 1H), 7.31 (m, 1H), 7.43 (m, 1H), 7.62 (m, 1H), 8.13 (m, 1H), 8.28 (m, 1H), 8.89 (s, 1H), 9.23 (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