Reaction Steps
To compound 24 (105 mg, 0.267 mmol) dissolved in anhydrous THF (15 mL) was added 1-piperidinepropionic acid (63 mg, 0.40 mmol), triethylamine (0.17 mL, 1.33 mmol), and BOP reagent (140 mg, 0.32 mmol), and the reaction mixture was allowed to stir at room temperature for 1.5 h. Reaction progress was monitored by TLC (50% CMA 80 in CH2Cl2). The reaction mixture was diluted with EtOAc (25 mL) and washed with saturated aqueous NaHCO3 (25 mL) followed by water (25 mL). The aqueous layers were back extracted with EtOAc (2×20 mL). The combined organic layers were washed with 1 N NaOH (25 mL), dried (MgSO4), and concentrated under reduced pressure to afford crude amide. The crude product was purified by flash chromatography (30% CMA 80 in CH2Cl2) to afford 121 mg (85%) of 25a as a shiny white solid: LCMS (ESI): m/z 532.8 (M+H)+; 1H NMR (CDCl3, 300 MHz) δ 8.77 [d, J=6 Hz, 1H], 7.15-7.30 [m, 8H], 6.72-6.75 [m, 1H], 4.24 [m, 1H], 3.82 [s, 3H], 2.76 [br, 1H], 2.65-2.68 [m, 2H], 2.42-2.56 [m, 3H], 2.32-2.37 [m, 6H], 2.07-2.30 [m, 7H], 1.62-1.83 [m, 5H], 1.59-1.61 [m, 4H], 1.48-1.59 [m, 4H], 1.25-1.27 [br, 1H], 1.21 [s, 3H]; 13C NMR (CDCl3, 300 MHz) δ 172.2, 159.2, 148.8, 142.8, 128.8, 128.7, 128.6, 126.0, 122.2, 116.2, 110.9, 62.4, 58.4, 55.6, 54.9, 54.0, 51.4, 45.5, 44.1, 38.1, 37.0, 36.8, 35.5, 34.0, 32.5, 29.2, 28.4, 26.9, 26.7, 24.6.
