反应详情

温度

50 °C

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

1. temperaturecooled to room temperature
2. washwashed with methanol (5 mL×2)
3. washThe obtained product was eluted with a 2 M methanol solution of NH3 (5 mL)
4. concentrationconcentrated
5. additionDichloromethane (2 mL) and phenyl isocyanate (0.10 mL) were added to the obtained residue
6. stirringthe resulting mixture was stirred at room temperature for 1 hour
7. washwashed with methanol (5 mL)
8. washThe obtained product was eluted with a 2 M methanol solution of NH3 (5 mL)
9. concentrationconcentrated
10. dissolutionThe residue was dissolved in methanol (0.25 mL)
11. additionand a 4 M dioxane solution of HCl (0.125 mL) was added to the resulting solution
12. stirringThe obtained mixture was stirred at room temperature overnight
13. concentrationconcentrated
14. dissolutionThe resulting residue was dissolved in methanol
15. washwashed with methanol (5 mL×2)
16. customThe obtained crude product
17. washwas eluted with a 2 M methanol solution of NH3 (5 mL)
18. concentrationconcentrated to thereby afford 4-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]-1-(3,4-diethoxybenzyl)piperidine (Compd. No