反应详情

A mixture of 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid (5 g, 13.5 mmol; prepared as described in Preparation 10), HATU (10.3 g, 27 mmol), 5-amino-1-pentanol (1.67 g, 16.2 mmol) and DIPEA (7.04 mL, 40.5 mmol) in 100 mL of DCM was stirred at room temperature for 1 hour. The reaction mixture was then washed with brine (100 mL), water (100 mL), dried over magnesium sulfate, filtered and concentrated. The residue was dissolved in DCM (100 mL) and cooled down to −5° C. in an ice/brine bath. DIPEA (7.04 mL, 40.5 mmol) and DMSO (10 mL) were added to the solution, followed by sulfur trioxide pyridine complex (6.45 g, 40.5 mmol). The reaction mixture was stirred at 0° C. for 2 hours and then washed with water (100 mL) and brine (2×100 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to yield 4.88 g of the title intermediate (80% yield) as a semi-solid.

1. washThe reaction mixture was then washed with brine (100 mL), water (100 mL)
2. dry with materialdried over magnesium sulfate
3. filtrationfiltered
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in DCM (100 mL)
6. temperaturecooled down to −5° C. in an ice/brine bath
7. stirringThe reaction mixture was stirred at 0° C. for 2 hours
8. washwashed with water (100 mL) and brine (2×100 mL)
9. dry with materialThe organic layer was dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated