A Novel One-Pot Synthesis of ۵-Nitro-[۳,۴'-bipyridin]-۶(۱H)-one as a Key Precursor for Amrinone Using ۲-Nitroacetamide and Improvement of the Classical Synthesis method of Amrinone

A new, efficient, and straightforward method for the synthesis of ۵-nitro-[۳,۴'-bipyridin]-۶(۱H)-one (۹), a key precursor of the cardiotonic drug amrinone, is reported. The key step involves a one-pot base-promoted condensation–cyclization reaction between ۳-(dimethylamino)-۲-(pyridin-۴-yl)acrylaldehyde (۲) and readily available ۲-nitroacetamide (۸) in ethanol in the presence of potassium hydroxide. The nitro precursor (۹) was obtained in ۸۹% yield and high purity. Additionally, ۲-nitroacetamide (۸) was prepared in excellent yield (۹۰%) via a simple, single-vessel procedure from ethyl chloroacetate. The final conversion of the nitro compound to amrinone was also improved by replacing hazardous bromine with safer and cheaper calcium hypochlorite in the Hofmann rearrangement step, achieving ۵۹% yield (versus ۳۰–۵۰% in classical methods). All compounds were fully characterized by FT-IR and ¹H NMR analysis.

کلیدواژه ها:

Amrinone ، ۲-nitroacetamide ، Hofmann rearrangement ، calcium hypochlorite