By employing microwave-assisted organic synthesis (MAOS) efficient conditions to introduce aminomethylene substituents in highly substituted bicyclic 2-pyridones have been established. Primary amino methylene substituents were introduced via a cyanodehalogenation followed by a borane dimethyl sulfide reduction of the afforded nitrile. In both of these transformations, microwave irradiation proved to be superior to traditional conditions and the primary amines were obtained in good overall yields (55-58% over three steps). To incorporate tertiary aminomethylene substituents in the 2-pyridone framework, a microwave-assisted Mannich reaction using preformed iminium salts proved to be effective. Thus highly substituted 2-pyridones were obtained in 48-93% yields.

Fused pyridine derivatives R 0450Microwave-Assisted Synthesis of Highly Substituted Aminomethylated 2-Pyridones. -Aminomethyl pyridones (IV) are prepared by cyanodehalogenation of bromides (I) and subsequent reduction of the nitriles (III) by borane dimethyl sulfide. In both steps microwave irradiation (MW) is applied. Unfortunately, a substantial loss in enantiomeric purity is observed for both steps leading to compound (IVb). To prepare tertiary aminomethyl-substituted pyridones, Mannich reaction of pyridones (V) with preformed iminium salts is accomplished under MW. In the case of pyridone (Vb), only little loss of enantiopurity of product (IXb) occurs. -(PEMBERTON, N.; AABERG, V.; ALMSTEDT, H.; WESTERMARK, A.; ALMQVIST*, F.; J. Org. Chem. 69 (2004) 23, 7830-7835; Dep. Chem., Org. Chem., Umea Univ., S-901 87 Umea, Swed.; Eng.) -Klein 12-156