反应详情

To a solution of 83 mg (0.17 mmol) of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)-N′-hydroxyacetimidamide (Example 82, Step C) in THF (4 mL) was added 50 mg (0.28 mmol) of 1,1′-thiocarbonyldiimidazole. The resulting yellow solution was stirred at room temperature for 1 h, and then was quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated. The residue was dissolved in THF (4.5 mL), and 69 μL (0.56 mmol) of boron trifluoride etherate was added via syringe. The resulting light yellow solution was stirred at room temperature for 2.5 h, and then was quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by reversed phase prep. HPLC (Sunfire Prep C18 OBD 10 μm column, gradient elution of 55% MeCN in water to 85% MeCN in water over a 35 min period, where both solvents contain 0.1% TFA) provided the title compound as a white solid.

1. customwas quenched with water
2. extractionextracted with EtOAc
3. dry with materialThe organic layer was dried over Na2SO4
4. filtrationfiltered
5. concentrationthe filtrate was concentrated
6. dissolutionThe residue was dissolved in THF (4.5 mL)
7. stirringThe resulting light yellow solution was stirred at room temperature for 2.5 h
8. customwas quenched with water
9. extractionextracted with EtOAc
10. dry with materialThe organic layer was dried over Na2SO4
11. filtrationfiltered
12. concentrationthe filtrate was concentrated
13. customPurification of the residue by reversed phase prep
14. washHPLC (Sunfire Prep C18 OBD 10 μm column, gradient elution of 55% MeCN in water to 85% MeCN in water over a 35 min period, where both solvents