反应详情

温度

50 °C

To a mixture of 4-[{N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl}aminomethyl]piperidine (0.050 mmol), 3,4-diethoxybenzaldehyde (0.15 mmol), methanol (1.2 mL), and acetic acid (0.050 mL) was added NaBH3CN (0.25 mmol) in methanol (0.50 mL). The reaction mixture was stirred at 50° C. overnight. The mixture was cooled to room temperature, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×2). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated. To the resulting material were added dichloromethane (2 mL) and phenyl isocyanate (0.10 mL) and the solution was stirred at room temperature for 1 h, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×2). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated. The residue was dissolved in methanol (0.25 mL) and 4 N HCl in dioxane (0.125 mL) was added. The solution was stirred at room temperature overnight and concentrated. The residue was dissolved in methanol, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×2). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated to afford 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(3,4-diethoxybenzyl)piperidine (Compound No. 2065) (21.2 mg, 84%): The purity was determined by RPLC/MS (97%); ESI/MS m/e 505.2 (M++H, C26H34F2N4O4).

1. temperatureThe mixture was cooled to room temperature
2. washwashed with CH3OH (5 mL×2)
3. washProduct was eluted off
4. concentrationconcentrated
5. additionTo the resulting material were added dichloromethane (2 mL) and phenyl isocyanate (0.10 mL)
6. stirringthe solution was stirred at room temperature for 1 h
7. washwashed with CH3OH (5 mL×2)
8. washProduct was eluted off
9. concentrationconcentrated
10. dissolutionThe residue was dissolved in methanol (0.25 mL)
11. addition4 N HCl in dioxane (0.125 mL) was added
12. stirringThe solution was stirred at room temperature overnight
13. concentrationconcentrated
14. dissolutionThe residue was dissolved in methanol
15. washwashed with CH3OH (5 mL×2)
16. washProduct was eluted off
17. concentrationconcentrated