反应详情

To a solution of [4-(2-morpholin-4-ylethoxy)-1-naphthyl]amine (0.60 g, 2.2 mmol) in DMF (2 ml) is added 3-fluoro-5-(4-methylpiperidin-1-yl)benzoic acid (0.63 g, 2.64 mmol), prepared from 4-methylpiperidine according to conditions described in general procedure E, HBTU (1.25 g, 3.3 mmol) and diisopropylamine (1.15 ml, 6.6 mmol). This mixture is stirred at room temperature overnight and diluted with CH2Cl2 (5 ml), washed with 0.05 N NaOH, dried over Na2SO4 and concentrated. The residue is purified by column chromatography on silica gel (90% EtOAc in hexane) to give 3-fluoro-5-(4-methylpiperidin-1-yl)-N-[4-(2-morpholin-4-ylethoxy)-1-naphthyl]benzamide as a white solid (0.53 g). Mp: 116-118° C.; 1H NMR (300 MHz, DMSO-d6) δ 0.91 (d, 6.3 Hz, 3H), 1.15-1.25 (m, 2H), 1.67 (d, J=12 Hz, 2H), 2.55 (bs, 4H), 2.74 (t, J=12.3 Hz, 2H), 2.86 (s, 2H), 3.59 (t, J=4.5 Hz, 4H), 3.82 (d, J=12.9 Hz, 2H), 4.29 (t, J=5.7 Hz, 2H), 6.93 (d, J=12.6 Hz, 1H), 7.00 (d, J=8.1Hz, 1H), 7.12 (d, J=8.7 Hz, 1H), 7.37-7.43 (m, 2H), 7.51-7.55 (m, 2H), 7.81-7.84 (m, 1H), 8.17-8.20 (m, 1H), 10.21 (s, 1H); MS 492 (M+1).

1. washwashed with 0.05 N NaOH
2. dry with materialdried over Na2SO4
3. concentrationconcentrated
4. customThe residue is purified by column chromatography on silica gel (90% EtOAc in hexane)