反应详情

A mixture of 1-benzyl-4-[N-propyl-N-(3-amino-2-pyridinyl)amino]piperidine (EXAMPLE 114, 0.35 g) in absolute ethanol (4.3 ml) under nitrogen is treated with acetaldehyde (120 μl) and sodium cyanoborohydride (84 mg) and the pH is adjusted to 5 with glacial acetic acid as measured on moistened pH test paper. The resulting mixture is stirred at 20°-25° for 48 hrs, during which additional acetaldehyde (180 μl) and sodium cyanoborohydride (70 mg) is added, and is then adjusted to pH 3 with hydrochloric acid (3M), neutralized with sodium hydroxide (5%), and concentrated under reduced pressure. The residue is chromatographed (silica gel, 70-230 mesh, 35 g; eluting with a gradient of methanol/methylene chloride (1/99-2/98)) to give the title compound, NMR (CDCl3) 7.72, 7.31, 7.27, 6.91, 6.79, 4.66, 3.51, 3.10, 2.92, 2.05, 1.74, 1.27 and 0.79δ.

1. additionis added
2. concentrationconcentrated under reduced pressure
3. customThe residue is chromatographed (silica gel, 70-230 mesh, 35 g
4. washeluting with a gradient of methanol/methylene chloride (1/99-2/98))