反应详情

To a stirred solution of Intermediate 348F (0.75 g, 1.731 mmol) in DMF (4.0 mL) was added NH4Cl (0.463 g, 8.66 mmol), HATU (1.316 g, 3.46 mmol) and DIPEA (1.512 mL, 8.66 mmol) and the resulting solution was stirred at RT for 16 h. The reaction mixture was diluted with ethyl acetate (10 mL), washed with water and brine. The organic layer was dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The crude compound was purified by silica gel chromatography (24 g REDISEP® column, eluting with 65% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate 348G as a colorless liquid (0.51 g, 68%). MS(ES): m/z=433 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 6.83-7.50 (m, 2H), 5.07 (d, J=18.13 Hz, 1H), 4.50 (d, J=18.51 Hz, 1H), 4.20 (d, J=2.27 Hz, 2H), 3.84 (br. s., 1H), 1.43 (s, 9H), 0.89 (d, J=9.82 Hz, 1H), 0.47 (d, J=7.93 Hz, 2H), 0.27-0.40 (m, 2H).

1. washwashed with water and brine
2. dry with materialThe organic layer was dried over Na2SO4
3. filtrationfiltered
4. concentrationthe filtrate concentrated under reduced pressure
5. customThe crude compound was purified by silica gel chromatography (24 g REDISEP® column, eluting with 65% EtOAc in hexanes)
6. additionFractions containing the product
7. customevaporated