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

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Reaction Steps

To the solution of 6-[4-(bromomethyl)phenyl]-2-chloro-5-phenylnicotinonitrile (2-5; 0.078 g, 0.203 mmol) in MeOH (1 mL) and THF (1 mL) was added 4-(2-keto-1-benzimidazolinyl)-piperidine (0.066 g, 0.305 mmol; commercially available) and DIEPA (0.131 g, 1.02 mmol). The mixture was stirred at rt overnight and concentrated. The residue was treated with aqueous Na2CO3 solution (5 mL, 2 M) and extracted with with CH2Cl2 (3×10 mL). The combined organic layer was dried, filtered and concentrated. The residue was purified by silica gel chromatography (3-5% 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 (2-6). 1H-NMR (500 MHz, CDCl3) δ 7.98 (s, 1H), 7.31-7.37 (m, 4H), 7.25-7.29 (m, 4H), 7.17-7.19 (m, 2H), 7.05-7.09 (m, 3H), 4.31-4.36 (m, 1H), 3.54 (s, 2H), 2.97-2.99 (m, 2H), 2.41-2.47 (m, 2H), 2.12-2.17 (m, 2H), 1.78-1.80 (m, 2H). LRMS m/z (M+H) Calcd: 520.0, found: 520.0.

Provenance & Evidence