Reaction Steps
To compound 24 (80 mg, 0.203 mmol) dissolved in anhydrous THF (15 mL) 3-(3,4-dihydro-1H-isoquinolin-2-yl)-propioinic acid hydrochloride (73 mg, 0.305 mmol), and triethylamine (0.142 mL, 1.01 mmol) was added, and the reaction mixture was stirred at room temperature for 15 min. After this time BOP reagent (99 mg, 0.22 mmol) was added, 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 layer was washed with 1 N NaOH (30 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 94 mg (80%) of 25b as a shiny white solid: LCMS (ESI): m/z 580.9 (M+H)+; 1H NMR (CDCl3, 300 MHz) δ 8.29 [d, J=6 Hz, 1H], 7.03-7.31 [m, 12H], 6.70-6.73 m, 1H], 4.23 [m, 1H], 3.80 [s, 1H], 3.68 [s, 2H], 2.94 [t, J=6 Hz, 2H], 2.77-2.82 [m, 4H], 2.62-2.67 [m, 3H], 2.42 [t, J=6 Hz, 2H], 2.25-2.35 [m, 2H], 1.74-1.87 [m, 7H], 1.19-1.34 [m, 3H], 1.14 [s, 3H]; 13C NMR (CDCl3, 300 MHz) δ 171.9, 159.2, 148.8, 142.8, 134.4, 134.1, 129.1, 128.9, 128.7, 128.6, 127.4, 126.9, 126.8, 126.3, 126.1, 122.1, 116.2, 110.8, 62.1, 58.2, 55.6, 54.1, 51.1, 50.5, 45.6, 44.0, 37.9, 36.8, 36.7, 35.3, 34.0, 33.0, 29.7, 29.2, 28.3, 26.8.
