Reaction Steps
A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 1e (100 mg, 0.515 mmol), 1p (203 mg, 0.469 mmol), N,N-diisopropylethylamine (242 mg, 1.88 mmol) and anhydrous DMF (2 mL). Benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP, 249 mg, 0.563 mmol) was added, and the reaction was heated at 60° C. for 16 h. After this time, the reaction was diluted with water (10 mL), and the resulting suspension was filtered. The filter cake was dissolved in methylene chloride (20 mL), and the solution was washed with 10% aqueous citric acid (10 mL), saturated aqueous sodium bicarbonate (10 mL), and water (10 mL), and dried over sodium sulfate. The drying agent was removed by filtration, and the solvent was evaporated under reduced pressure. The resulting residue was eluted with a gradient from 0% to 20% of methanol in ethyl acetate, and the fractions containing 1q were collected to afford, after concentrating under reduced pressure, a 44% yield (127 mg) of 1q as an off-white solid: mp 178-179° C.; 1H NMR (500 MHz, CD2Cl2) δ 8.35 (s, 1H), 7.85 (d, 1H, J=8.0 Hz), 7.77 (d, 2H, J=8.5 Hz), 7.59 (s, 1H), 7.42 (s, 1H), 7.29-7.22 (m, 4H), 6.76 (s, 1H), 3.68 (td, 1H, J=11.5, 4.5 Hz), 3.62-3.60 (m, 2H), 3.58 (s, 3H), 3.47 (m, 1H), 3.18 (m, 1H), 2.97 (m, 1H), 2.91 (s, 3H), 2.64 (m, 1H), 2.39 (s, 3H), 2.13 (s, 3H), 1.98-1.90 (m, 3H), 1.67 (dt, 1H, J=9.0, 2.5 Hz), 1.10 (dd, 2H, J=12.5, 3.5 Hz); MS (ESI+) m/z 609.3 (M+H).
