General procedure for the synthesis of (E)-N-(2-(2-(2-(trifluoromethyl)-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide (15d): Compound 13b (480 mg, 2.1 mmol) was dissolved in dichloromethane (10 mL) at room temperature, and sequentially added (E)-3-(3,4,5-trimethoxyphenyl ) acrylic acid (14a) (504 mg, 2.1 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI) (523 mg, 2.73 mmol) and N,N-dimethylaminopyridine (DMAP) (10 mg). The reaction mixture was stirred at room temperature for 8 hours. Upon completion of the reaction, the reaction was quenched with water (10 mL) and the product was extracted with ethyl acetate (20 mL × 3). The organic phases were combined and washed sequentially with 1% HCl (10 mL), saturated NaHCO3 solution (10 mL), water (20 mL), and brine (20 mL), then dried with anhydrous Na2SO4. After concentration under reduced pressure, the crude product was purified by silica gel column chromatography with the eluent being a hexane solution of 0-35% ethyl acetate to give the target product 15d (700 mg, 74% yield). The 1H NMR (CDCl3) data of product 15d: δ 7.59 (d, J = 8 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 15.2 Hz, 1H), 7.27 (q, J = 7.2 Hz, 1H), 7.1 (t, J = 7.2 Hz, 1H), 6.89 (s, 1H), 6.63 (s, 2H), 6.4 (t, J = 6 Hz, 1H), 6.25 (d, J = 15.2 Hz, 1H), 4.4 (t, J = 6.4 Hz, 1H), 3.8 (s, 3H), 3.76 (s, 6H), 3.69 (q, J = 6.4 Hz, 2H). lCMS (ESI) analysis: λ254 nm, MS purity > 95%; m /z 449 [M + H]+. Calculated elemental analysis (C23H23F3N2O4): C, 61.60; H, 5.17; N, 6.25; measured values: C, 61.34; H, 5.10; N, 6.16.
