Benzoyl Peroxide → 2-Chloro-6-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl]-5-phenylnicotinonitrile

Participants

Reaction Steps

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.

Provenance & Evidence