反应详情

To a suspension of 4-{[3-(1-azetidin-3-yl-1H-pyrazol-5-yl)-2′-(trifluoromethyl)biphenyl-4-yl]oxy}-5-chloro-2-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 46, 42.9 mg, 0.0659 mmol) in methanol (0.10 mL), dichloromethane (1.72 mL) and acetic acid (0.10 mL) was added formaldehyde (37% w/w, 16.7 μL, 0.224 mmol). The reaction was then stirred under nitrogen at room temperature for 45 minutes. Sodium triacetoxyborohydride (42.6 mg, 0.201 mmol) was added to the reaction which was stirred for 18 hours at room temperature. The reaction was diluted with dichloromethane (20 mL) and washed with water (3×2 mL). The combined aqueous phases were extracted with dichloromethane (3×5 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a white solid (58.0 mg). The solid was purified by B-HPLC to afford the title compound.

1. stirringwas stirred for 18 hours at room temperature
2. washwashed with water (3×2 mL)
3. extractionThe combined aqueous phases were extracted with dichloromethane (3×5 mL)
4. dry with materialThe combined organic phases were dried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo