Reaction Steps
To a suspension of 2-aminobenzimidazole (81 mg, 0.61 mmol) in CH2Cl2 (5 mL) and DMF (0.5 mL) was added 1,1′-carbonyldiimidazole (99 mg, 0.61 mmol) and the reaction stirred at reflux for 30 min. then at room temperature for 2 h after which a solution of (3,5-dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidine-4-yl-amine (109 mg, 0.31 mmol) in DMF (1 mL) was added and the reaction stirred at 65° C. overnight. The solution was cooled, treated with saturated aqueous NaHCO3 (25 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were washed with brine (1×30 mL), dried (Na2SO4), filtered, and concentrated. Purification of the crude material by radial chromatography on silica gel (1 mm plate, CH2Cl2/MeOH/NH4OH, 100:1:1 then 50:1:1 then 25:1:1) provided COMPOUND 285 (158 mg, 99%) as a white foam: 1H NMR (CDCl3) δ 0.90 (d, 6H, J=6.9 Hz), 1.60-1.70 (m, 2H), 1.87-1.92 (m, 2H), 2.14 (s, 3H), 2.27 (s, 3H), 2.67-2.80 (m, 4H), 3.74 (s, 2H), 3.81 (s, 2H), 4.39-4.44 (m, 2H), 7.10-7.17 (m, 3H), 7.23 (s, 1H), 7.30 (dd, 2H, J=6, 3.3 Hz), 7.48 (dd, 1H, J=7.8, 1.5 Hz), 8.17 (s, 1H), 8.31 (dd, 1H, J=4.8, 1.5 Hz). 13C NMR (CDCl3) δ 17.80, 18.00, 23.09, 26.85, 27.07, 44.32, 53.78, 56.96, 121.63, 122.66, 131.76, 132.74, 133.37, 138.57, 143.90, 145.53, 146.09, 151.84, 153.97, 155.79, 157.81. ES-MS m/z 512 (M+H). Anal. Calcd. for C30H37N7O.1.0CH2Cl2: C, 62.41; H, 6.59; N, 16.43. Found: C, 62.18; H, 6.60; N, 16.27.
