To a mixture of the product of Example 68E (225 mg, 0.73 mmol), 4-(3,4-difluorophenoxy)piperidine (155 mg, 0.73 mmol), and 4-(dimethylamino)pyridine (8.9 mg, 0.07 mmol) in CH2Cl2 (3 mL) at ambient temperature was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.129 mL, 0.727 mmol) via syringe. The reaction was stirred for 18 hours, then diluted with 50 mL CH2Cl2 and washed with 1 N aqueous HCl, saturated aqueous NaHCO3 solution and brine, dried with Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (Analogix® Intelliflash™ 280; SF15-24 g column; 50% ethyl acetate/hexanes). Hexanes (20 mL) were added and the flask was placed in an ultrasonic bath for 10 minutes resulting in a milky mixture. Ether (6 mL) was added to help precipitate the solid, which was collected by vacuum filtration and air-dried to give the titled compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.39-7.15 (m, 10H), 7.06 (dd, J=19.1, 9.1, 1H), 6.72 (ddd, J=11.9, 6.6, 3.0, 1H), 6.64-6.55 (m, 1H), 4.49-4.32 (m, 2H), 4.11 (d, J=15.6, 1H), 3.80-3.33 (m, 6H), 2.73-2.56 (m, 2H), 2.01-1.72 (m, 6H); MS (ESI+) m/z 505 (M+H)+.
