反应详情

Add hydrochloric acid (10 mL, 40.0 mmol, 4 M in 1,4 dioxane) to tert-butyl N-[[6-(difluoromethyl)-5-[[4-methyl-5-[4-(trifluoromethyl)phenyl]-1H-imidazol-2-yl]carbamoyl]-3-pyridyl]methyl]carbamate (0.212 g, 0.403 mmol) and stir overnight. Dilute with water, and extract with Et2O. Adjust the pH to ˜8 with a saturated sodium bicarbonate aqueous solution. Extract with EtOAc (3×30 mL). Dry the organic extracts over sodium sulfate; filter; collect the filtrate; and concentrate the filtrate under reduced pressure. Purify by reverse phase flash chromatography (Analogix® 40 g @ 40 mL/min) eluting with a gradient of 2-55% ACN/water over 30 minutes. Concentrate the appropriate fractions under reduced pressure until all the ACN is removed and only water remains. Add a saturated sodium bicarbonate aqueous solution (30 mL), and extract with EtOAc (3×20 mL). Dry the organic extracts over sodium sulfate; filter; collect the filtrate; and concentrate the filtrate under reduced pressure to give the title compound as a light yellow solid (0.098 g, 57% yield). 1H NMR (400.43 MHz, d6-DMSO) δ 8.71-8.69 (m, 1H), 8.16 (s, 1H), 7.79-7.77 (m, 2H), 7.69-7.67 (m, 2H), 7.42-7.28 (m, 1H), 3.81 (s, 2H), 2.43 (s, 3H).

1. extractionextract with Et2O
2. extractionExtract with EtOAc (3×30 mL)
3. dry with materialDry the organic extracts over sodium sulfate
4. filtrationfilter
5. customcollect the filtrate
6. concentrationand concentrate the filtrate under reduced pressure
7. customPurify by reverse phase flash chromatography (Analogix® 40 g @ 40 mL/min)
8. washeluting with a gradient of 2-55% ACN/water over 30 minutes
9. concentrationConcentrate the appropriate fractions under reduced pressure until all the ACN
10. customis removed
11. additionAdd a saturated sodium bicarbonate aqueous solution (30 mL)
12. extractionextract with EtOAc (3×20 mL)
13. dry with materialDry the organic extracts over sodium sulfate
14. filtrationfilter
15. customcollect the filtrate
16. concentrationand concentrate the filtrate under reduced pressure