反应详情

温度

20 °C

To a stirred solution of [7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]acetaldehyde (D88) (50 mg), 3-azetidinecarboxylic acid (25 mg) and acetic acid (0.1 mL) in DCM (10 mL) was added sodium triacetoxyborohydride (78 mg). The reaction was stirred at 20° C. for 3 h. The mixture was concentrated and the residue was partitioned between ethyl acetate (25 mL) and aqueous HCl (2 M, 25 mL). The organic phase was washed with water (25 mL) and brine (25 mL), dried over sodium sulphate and evaporated to give the crude product, which was purified by Mass Directed Auto Prep to afford 1-{2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}-3-azetidinecarboxylic acid (E67) (18 mg, TFA salt). δH (DMSO-d6, 400 MHz): 1.36 (6H, d), 3.00 (2H, t), 3.47 (2H, t), 3.60 (1H, m), 3.65 (3H, s), 4.22 (4H, m), 4.88 (1H, m), 7.22 (1H, t), 7.31 (1H, s), 7.47 (2H, m), 7.87 (1H, dd), 8.12 (1H, dd), 8.19 (1H, d). MS (ES): C26H27ClN4O4 requires 494; found 495.2 (M+H+).

1. concentrationThe mixture was concentrated
2. customthe residue was partitioned between ethyl acetate (25 mL) and aqueous HCl (2 M, 25 mL)
3. washThe organic phase was washed with water (25 mL) and brine (25 mL)
4. dry with materialdried over sodium sulphate
5. customevaporated
6. customto give the crude product, which
7. customwas purified by Mass Directed Auto Prep