反应详情

温度

0 °C

To a solution containing Boc-Chg-OH (600 mg, 2.3 mmol) in anhydrous NMP (6 mL) was cooled to 0° C. HATU (865 mg, 2.3 mmol) and DIPEA (0.67 g, 5.2 mmol) were added followed by the addition of crude 42 (900 mg, 2.4 mmol) in anhydrous NMP (6 mL). The reaction mixture was slowly warmed to ambient temperature. After 16 h, the reaction mixture was diluted with EtOAc and washed successively with 1M HCl, aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 1.5 g of crude 48 as a light brown-colored foam which was used without further purification. 1H NMR (300 MHz, CDCl3), mixture of rotamers: δ8.38 (s, 0.5H), 8.31 (s, 0.5H), 8.19 (dd, J=5.4, 8.7 Hz, 0.5H), 8.12 (dd, J=5.4, 8.7 Hz, 0.5H), 7.44-7.35 (m, 5H), 7.00-6.88 (m, 2H), 6.78 (s, 0.5H), 6.61 (s, 0.5H), 5.38-5.28 (m, 1H), 5.22-5.12 (m, 2H), 4.65 (d, J=4.8 Hz, 0.5H), 4.58 (d, J=5.1 Hz, 0.5H), 4.39-4.31 (m, 2H), 4.23 (d, J=11.7 Hz, 0.5H), 4.16-4.02 (m, 2H), 3.92 (d, J=5.4 Hz, 1H), 3.54-3.43 (m, 2H), 2.47-2.37 (m, 0.5H), 2.29-2.23 (m, 0.5H), 1.93-1.70 (m, 7H), 1.43 (s, 9H), 1.19-1.12 (m, 2H) ppm. Mass spectrum, m/z [619.5] (M+H)+.

1. temperatureThe reaction mixture was slowly warmed to ambient temperature
2. washwashed successively with 1M HCl, aqueous NaHCO3, and brine
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated