反应详情

To a solution of compound 4 (11.7 g; 31 mmol) in dry DMF (100 mL) was added EDCI (7.25 g; 37.82 mmol), HOBt (5.79 g; 37.82 mmol), and the reaction mixture was stirred at room temperature for 30 min (solution A). In the meantime, to a solution of compound 9 (8.67 g: 31 mmol) in dry DMF (100 mL) kept at 0° C. was added DIEA (10.01 g; 77.7 mmol) and stirred for 30 min (solution B). Solution B was mixed with solution A and the reaction mixture was stirred overnight at room temperature. The solvent was removed on the rotary evaporator and the residue was taken up in ethyl acetate (300 mL) and washed sequentially with saturated sodium bicarbonate (2×75 mL), 5% HCl (2×75 mL) and brine (75 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated, yielding a crude product which was purified using recrystallization to yield 9 as an off white solid (8.3 g; 46% yield). NMR (CDCl3) δ 8.1 (s, 1H), 7.9 (s, 1H), 7.8 (s, 1H), 7.5 (s, 1H) 7.3 (m, 5H), 5.0 (s, 2H), 4.3 (m, 1H), 4.1 (m, 1H), 3.3 (t, 1H), 2.8 (s, 1H), 2.4 (d, 2H), 2.2 (d, 2H), 2.1 (m, 2H), 1.9 (m, 2H), 1.8 (m, 2H), 1.6 (m, 2H), 1.4 (m, 1H), 0.8 (d, 6H)

1. customkept at 0° C.
2. customThe solvent was removed on the rotary evaporator
3. washwashed sequentially with saturated sodium bicarbonate (2×75 mL), 5% HCl (2×75 mL) and brine (75 mL)
4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated