GENERAL STEPS: To a solution of 1,2-cyclohexanedione (2243 mg, 20 mmol) and concentrated hydrochloric acid (13 mL) in acetic acid (40 mL) was slowly added dropwise to a solution of p-toluene hydrazine hydrochloride (1586 mg, 10 mmol) in methanol (25 mL), with dropwise addition time being controlled to within 10 minutes. After the dropwise addition, the reaction mixture was heated to 60 °C and the reaction was stirred overnight. Upon completion of the reaction, the solvent was removed by evaporation and the residue was adjusted to weak basicity with saturated NaHCO3 solution. Subsequently, the mixture was extracted with ethyl acetate (3 x 20 mL). The organic phases were combined, washed with brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate, 12:1 v/v) to give Intermediate 7 (1235 mg, 62% yield) as a brown powder. A mixture of Intermediate 7 (102 mg, 0.5 mmol), 4-phenylbutylamine (0.12 mL, 0.8 mmol) and a catalytic amount of p-toluenesulfonic acid (p-TsOH) in toluene (10 mL) was reacted by refluxing for 16 h at 140 °C using a Dean-Stark manifold. At the end of the reaction, the solvent was removed by evaporation and the residue was dissolved in methanol. NaBH4 (177 mg) was added to the solution at 0 °C and the solution was then heated to 80 °C until TLC showed that the reaction was complete. The reaction solution was quenched with water and concentrated. Subsequently, the mixture was extracted with ethyl acetate (2 x 20 mL), the organic layers were combined and dried with anhydrous Na2SO4. After evaporation of the solvent, the resulting residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate, 4:1 v/v) to afford the target compound 5 (123 mg, 72% yield).1H NMR (300 MHz, CDCl3) δ 8.23 (s, 1H), 7.33-7.27 (m, 2H), 7.26-7.23 (m, 1H), 7.23- 7.11 (m, 4H), 6.99-6.92 (m, 1H), 3.97-3.85 (m, 1H), 2.89-2.77 (m, 1H), 2.71-2.63 (m, 4H), 2.63-2.59 (m, 1H), 2.44 (s, 3H), 2.28-2.14 (m, 1H), 2.08-1.95 (m, 1H), 1.83-1.95 (m, 1H), 2.08-1.95 (m, 1H), 2.08-1.95 (m, 1H), 2.08-1.95 (m, 1H), 1.08-1.95 (m, 1H) 1H), 1.83-1.65 (m, 4H), 1.63-1.48 (m, 4H). 13C NMR (125 MHz, DMSO-d6) δ 142.28, 136.74, 134.21, 128.29, 128.18, 127.10, 126.27, 125.57, 121.96, 117.38, 110.68, 108.76, 51.61, 46.07, 35.22, 29.72 , 29.34, 28.92, 21.27, 20.89, 20.76. HRMS (ESI): Calcd for C23H29N2 [M + H]+: 333.2331; Found: 333.2328.
