反应详情

To a solution of [3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]acetaldehyde (D15) (73 mg) and 3-pyrrolidinecarboxylic acid (72.4 mg) in dichloromethane (DCM) (10 mL) stirred at room temperature was added AcOH (0.15 mL). The reaction mixture was stirred at room temperature for 10 min. Then sodium triacetoxyborohydride (66.6 mg) was added. Stirring continued for overnight. Water was added to quench the reaction, and DCM was removed by evaporation. The mixture was extracted by EA for 3 times. The combined organic solution was washed by brine, dried over anhydrous Na2SO4. The dried solution was filtered and concentrated, the residue was purified by Mass Directed AutoPrep to give 1-{2-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]ethyl}-3-pyrrolidinecarboxylic acid (E12) (27 mg) as a TFA salt (off-white solid). δH (DMSO-d6, 400 MHz): 1.13 (3H, t), 1.35 (6H, d), 2.23 (1H, m), 2.86 (2H, m), 3.10 (2H, m), 3.22 (2H, m), 3.48 (4H, m), 3.72 (1H, m), 3.87 (1H, m), 4.84 (1H, m), 7.39 (2H, dd), 7.50 (2H, m), 7.96 (1H, dd), 8.10 (1H, d), 9.95 (1H, br s), 12.97 (1H, br s). δF (DMSO-d6, 376 MHz): −73.5. MS (ES): C26H30ClN3O3S requires 499. found 500.1 (M+H+).

1. stirringStirring
2. waitcontinued for overnight
3. customto quench
4. customthe reaction, and DCM
5. customwas removed by evaporation
6. extractionThe mixture was extracted by EA for 3 times
7. washThe combined organic solution was washed by brine
8. dry with materialdried over anhydrous Na2SO4
9. filtrationThe dried solution was filtered
10. concentrationconcentrated
11. customthe residue was purified by Mass Directed AutoPrep