反应详情

温度

0 °C

To a solution containing Cbz-N(Me)Ala-OH (196 mg, 0.83 mmol) and crude 15 (307 mg, 0.76 mmol) in anhydrous NMP (3 mL) was cooled to 0° C. HATU (315 mg, 0.83 mmol) and DIPEA (118 mg, 0.91 mmol) were added and the reaction mixture was slowly warmed to ambient temperature. After 16 h, the reaction mixture was diluted with diethyl ether and EtOAc (1:4) and washed successively with 1M HCl, aqueous NaHCO3, water, and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 420 mg (88%) of crude 16 which was used without further purification. 1H NMR (CDCl3, 300 MHz), mixture of rotomers: δ7.37-7.25 (m, 9H), 6.96 (m, 1H), 6.69 (br s, 1H), 5.19 (m, 2H), 4.91 (m, 1H), 4.81 (m, 1H), 4.58-4.46 (m, 2H), 4.04 (m, 2H), 3.97 (app d, J=12.6 Hz, 0.5H), 3.84 (app d, J=12.6 Hz, 0.5H), 3.40-3.25 (m, 2H), 2.88 (s, 3H), 2.48 (dd, J=5.7, 13.5 Hz, 0.5H), 2.33 (dd, J=5.4, 12.9 Hz, 0.5H), 2.06-1.82 (m, 2H), 1.51 (s, 4.5H), 1.49 (s, 4.5H), 1.36 (d, J=6.9 Hz, 3H), 0.91 (dd, J=2.7, 6.6 Hz, 3H), 0.83 (dd, J=1.8, 6.9 Hz, 3H) ppm.

1. temperaturethe reaction mixture was slowly warmed to ambient temperature
2. washwashed successively with 1M HCl, aqueous NaHCO3, water, and brine
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customto afford 420 mg (88%) of crude 16 which
7. customwas used without further purification