反应详情

(4-Aminonaphthalen-1-yloxy)-acetonitrile (1.068 g, 5.4 mmol), 3-fluoro-5-(4-methylpiperidin-1-yl)-benzoic acid (1.27 g, 5.4 mmol), diisopropylethylamine (3 ml) and HBTU (2.45 g, 6.5 mmol) are stirred at room temperature in anhydrous dimethylformamide (20 ml) for 1 day. The mixture is then poured into ethyl acetate (200 ml) and washed with water (2×200 ml). The organic layer is then dried over anhydrous sodium sulfate and evaporated to dryness. The residue is purified by column chromatography on silica gel eluted with 25-30% ethyl acetate in hexanes to give a pale purple solid. This is then recrystallized from ethyl acetate/methanol to give N-(4-cyanomethoxynaphthalen-1-yl)-3-fluoro-5-(4-methylpiperidin-1-yl)-benzamide as a pale purple solid (303 mg). 1H NMR 300 MHz (CDCl3) 8.27 (d, 1H, J=7.5 Hz), 7.94 (s, 1H), 7.86 (t, 2H, J=9.6 Hz), 7.6 (m, 2H), 7.3 (s, 1H), 6.97 (m, 2H), 6.77 (d, 1H, J=11.4 Hz), 5.0 (s, 1H), 3.77 (m, 2H), 2.83 (m, 2H), 1.75 (m, 2H), 1.25-1.4 (m, 3H), 1.0 (d, 3H).

1. washwashed with water (2×200 ml)
2. dry with materialThe organic layer is then dried over anhydrous sodium sulfate
3. customevaporated to dryness
4. customThe residue is purified by column chromatography on silica gel
5. washeluted with 25-30% ethyl acetate in hexanes
6. customto give a pale purple solid
7. customThis is then recrystallized from ethyl acetate/methanol