反应详情

A mixture of 2-chloro-6-(4-methylphenyl)-5-phenylnicotinonitrile (11-4) (1.78 g, 5.84 mmol), NBS (1.14 g, 6.42 mmol) and benzoylperoxide (0.28 g, 1.17 mmol) in chloroform (25 mL) was heated to reflux for 24 h. Concentrated in vacuo and the residue was dissolved in MeOH (15 mL) and THF (15 mL). To this solution was added 4-(2-keto-1-benzimidazolinyl)-piperidine (1.39 g, 6.42 mmol) and diisopropylethylamine (3.8 g, 29.2 mmol). The mixture was stirred overnight and concentrated. The residue was treated with Na2CO3 (20 mL, 2M) and extracted with CH2Cl2. The combined organic layers was dried, filtered and concentrated in vacuo. The solid was purified by silicon gel chromatography (2–4% MeOH in CH2Cl2) to give 2-chloro-6-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-5-phenylnicotinonitrile (11-5). 1H NMR (CDCl3) δ 8.70 (s, 1H), 7.98 (s, 1H), 7.37–7.25 (m, 7H), 7.17–7.19 (m, 2H), 7.03–7.09 (m, 4H), 4.31–4.37 (m, 1H), 3.54 (s, 2H), 2.98 (m, 2H), 2.41–2.46 (m, 2H), 2.13–2.18 (m, 2H), 1.78–1.80 (m, 2H). LRMS m/z (M+H) Calcd: 520.0, found: 520.2.

1. temperaturewas heated
2. temperatureto reflux for 24 h
3. concentrationConcentrated in vacuo
4. dissolutionthe residue was dissolved in MeOH (15 mL)
5. concentrationconcentrated
6. additionThe residue was treated with Na2CO3 (20 mL, 2M)
7. extractionextracted with CH2Cl2
8. customThe combined organic layers was dried
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe solid was purified by silicon gel chromatography (2–4% MeOH in CH2Cl2)