Reaction Steps
To a solution containing Boc-Chg-OH (167 mg, 0.64 mmol) in anhydrous NMP (6 mL) was cooled to 0° C. HATU (247 mg, 0.64 mmol) and DIPEA (94 mg, 0.73 mmol) were added followed by the addition of crude 49 (300 mg, 0.62 mmol). The reaction mixture was slowly warmed to ambient temperature. After 16 h, the reaction mixture was diluted with diethyl ether and washed successively with water, 1M HCl, water, aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by flash silica gel chromatography (2:1-1:1 hexanes/EtOAc) to afford 370 mg (82%) of 121 as a white solid. 1H NMR (300 MHz, CDCl3), mixture of rotomers: δ8.32 (dd, J=5.4, 8.7 Hz, 0.4H, minor rotomer), 8.21 (dd, J=5.7, 9.0 Hz, 1.6H, major rotomer), 8.12 (br s, 0.4H), 8.06 (br s, 1.6H), 7.06 (m, 2H), 7.01 (m, 2H), 6.98 (m, 2H), 6.94 (m, 2H), 5.31 (app d, J=9.3 Hz, 2H), 5.22 (app d, J=9.6 Hz, 2H), 4.60 (d, J=5.1 Hz, 2H), 4.46-4.32 (m, 10H), 4.04 (d, J=5.7 Hz, 2H), 3.64 (dd, J=6.0, 10.8 Hz, 2H), 3.33 (m, 2H), 2.43 (dd, J=5.4, 13.4 Hz, 2H), 1.89-1.55 (m, 10H), 1.47 (s, 3.6H, minor rotomer), 1.44 (s, 14.4H, major rotomer), 1.28-1.02 (m, 10H) ppm. Mass spectrum, m/z [724.5] (M+H)+.
