Byproduct isolation and characterization from reductive amination reaction in the synthesis of PEPCK inhibitors

ORGN 483

Shiming Li, shiming.li@roche.com, Department of Food Science, Rutgers University, 65 Dudley Rd, New Brunswick, NJ 08901
In the synthesis of phosphoenolpyruvate carboxykinase (PEPCK) inhibitors for treatment of diabetes, a reductive amination reaction was performed. Thus, the reaction of substituted benzaldehyde and 2-ethyl-2H-pyrazol-3-ylamine under the condition of sodium triacetoxyborohydride and catalytic amount of acetic acid and methylene chloride as solvent yielded desired product, substituted benzyl-(2-ethyl-2H-pyrazol-3-yl)-amine, and a undesired byproduct. To study the mechanism of the side reaction, the byproduct was isolated by reverse phase HPLC. The structure was characterized by various spectroscopic methods. The byproduct was identified as bis-(5-amino-1-ethyl-1H-pyrazol-3-yl)-methyl-phenyl moiety, which indicates the carbon-carbon bond formation between the aldehyde and the amine.