Cyclohexanone → (R)-6-(1-cyclohexyl-1,2,3,6-tetrahydropyridin-4-yl)-1-(1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazole

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Reaction Steps

To a stirred solution of the crude (R)-1-(1-(2,4-dichlorophenyl)ethyl)-6-(1,2,3,6-tetrahydropyridin-4-yl)-1H-benzo[d]imidazole (prepared from Example 4 step d, 0.047 g, 0.13 mmol) and cyclohexanone (0.0.038 g, 0.38 mmol) in dichloromethane (1 mL) was added sodium triacetoxyborohydride (NaBH(OAc)3, 0.11 g, 0.52 mmol) and acetic acid (3 drops). The reaction mixture was stirred at room temperature for 18 h, and quenched with saturated aqueous sodium bicarbonate. The mixture was extracted with dichloromethane (2×15 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The resulting crude material was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give a white solid (0.015 g, 0.032 mmol, 25%). 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1 H), 7.69 (d, J=8.4 Hz, 1 H), 7.44 (d, J=2.4 Hz, 1 H), 7.32 (dd, J=1.2, 8.4 Hz, 1 H), 7.12 (dd, J=2.4, 8.4 Hz, 1 H), 7.06 (s, 1 H), 6.82 (d, J=8.4 Hz, 1 H), 5.99-5.94 (m, 2 H), 3.30 (d, J=2.8 Hz, 2 H), 2.81-2.78 (m, 2 H), 2.58-2.48 (m, 2 H), 2.38-2.36 (m, 1 H), 1.97 (d, J=6.8 Hz, 3 H), 1.94-1.82 (m, 4 H), 1.67-1.64 (m, 1 H), 1.31-1.26 (m, 4 H), 1.15-1.11 (m, 1 H); MS: (ES) m/z calculated for C26H30Cl2N3 [M+H]+ 454.2, found 453.

Provenance & Evidence