Efficient synthesis of 3-cyano-6-(2-hydroxyphenyl)pyridines by multi-component condensations on beads

An efficient procedure to perform pyridine ring closure reactions has been developed on beads. A certain number of hydroxyacetophenones were immobilized on Wang resin and condensed with a variety of aldehydes and malononitrile in the presence of ammonium acetate to give 3-cyano-6-(2-hydroxyphenyl)pyridines in a suitable manner for a good example of combinatorial approaches. Chemical yields were better than the corresponding solution-phase chemistry except only a few examples and the best use of inherent advantage of solid-phase chemistry was successfully demonstrated.