Acetic Acid → 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(3,4-diethoxybenzyl)piperidine

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反応条件

反応手順

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).

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