反应详情

To a solution of [5-fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]acetaldehyde (D35) (90 mg) and 3-azetidinecarboxylic acid (80 mg) in dichloromethane (DCM) (20 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 (84 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/THF/MeCN 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-[5-fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]ethyl}-3-azetidinecarboxylic acid (E14) (45 mg) as an off-white solid. δH (DMSO-d6, 400 MHz): 1.34 (6H, d), 2.69 (4H, m), 3.17 (3H, m), 3.41 (2H, m), 3.79 (3H, s), 4.94 (1H, m), 7.43 (1H, dd), 7.52 (1H, d), 7.88 (1H, dd), 8.27 (2H, m). δF (DMSO-d6, 376 MHz): −117.2, −61.3. MS (ES): C25H25F4N3O4S requires 539. found 540.1 (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/THF/MeCN 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