反应详情

Into a solution of 4-((2R)-2-{[[(2S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-(phenyloxy)propyl](phenylmethyl)amino]methyl}-3,4-dihydro-2H-chromen-6-yl)-2-pyridinecarboxylic acid (Example 90, 82 mg, 0.13 mmol) in dichloromethane (2 mL) was added 4-fluorobenzylamine (33 mg, 0.26 mmol, 2.0 eq.), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (50 mg, 0.26 mmol, 2.0 eq.), and 1-hydroxybenzotriazole (35 mg, 0.26 mmol, 2.0 eq.). The solution was stirred overnight at room temperature before being concentrated in vacuo to remove volatile components. The crude residue was purified by flash chromatography on silica gel eluted with 75:25 hexanes/ethyl acetate. The title compound was obtained as a yellow oil (34 mg, 35%): 1H NMR (300 MHz, CDCl3) δ8.47 (d, 1 H), 8.40 (s, 2 H), 7.55 (dd, 1 H), 7.44-7.39 (m, 2 H), 7.34-7.29 (m, 4 H), 7.25-7.20 (m, 4 H), 7.01 (t, 2 H), 6.93-6.80 (m, 4 H), 4.64 (d, 2 H), 4.22-4.16 (m, 1 H), 4.11-4.05 (m, 1 H), 3.83 (s, 2 H), 3.75 (dd, 1 H), 2.94-2.80 (m, 2 H), 2.73-2.67 (m, 4 H), 1.71-1.57 (m, 2 H), 0.86 (s, 9H), 0.09 (s, 3 H), 0.05 (s, 3 H); MS m/z 746.5 (M+).

1. concentrationbefore being concentrated in vacuo
2. customto remove volatile components
3. customThe crude residue was purified by flash chromatography on silica gel
4. washeluted with 75:25 hexanes/ethyl acetate