反应详情

A mixture of 1-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-piperidin-3-ylmethylurea hydrochloride (35 mg, 100 μmol), 3-(4-fluorophenyl)-propionaldehyde (15 mg, 100 μmol), triethylamine (15 μL, 110 μmol), resin-bound cyanoborohydride (prepared according to Ley, S. V., et al., J. Chem. Soc. Perkin Trans. 1, 1998, 2239; 100 mg), toluene (1 mL) and methanol (1 mL) was agitated gently at room temperature for 65 hours. The mixture was filtered, the resin was washed with dichloromethane, and the filtrates were concentrated. The residue was purified by flash chromatography, eluting with 4% methanol in dichloromethane containing 0.4% aqueous ammonium hydroxide, to provide an amorphous white solid (29 mg, 64%). 1H NMR (300 MHz, CDCl3) δ7.88 (s, 1H), 7.79 (d, J=8 Hz, 1H), 7.44 (t, J=8 Hz, 1H), 7.27 (m, 1H), 7.11 (m, 2H), 6.93 (t, J=9 Hz, 2H), 4.18 (s, 3H), 3.2-3.0 (m, 4H), 2.59 (m, 4H), 2.3-1.8 (m, 8H), 1.10 (m, 1H). Mass Spec (ES+) m/z 452.4 (M+H+, 100%).

1. filtrationThe mixture was filtered
2. washthe resin was washed with dichloromethane
3. concentrationthe filtrates were concentrated
4. customThe residue was purified by flash chromatography
5. washeluting with 4% methanol in dichloromethane containing 0.4% aqueous ammonium hydroxide