Pyridine derivatives are an important part of the repertoire in the discovery of new pharmaceuticals and
agrochemicals. In this regard, combinatorial chemistry can be a powerful tool. The Kröhnke synthesis of
2,4,6-trisubstituted pyridines is ideal for combinatorial applications, since reactions generally proceed in
high yields on solid phase, and three points of diversity can be independently varied. A 220-member Kröhnke
pyridine library was prepared on JandaJel using a combined split-mix and parallel strategy affording 55
pools of four members each after cleavage from the resin. The library was analyzed by HPLC and LC/MS
that indicated 85% of the pools were of good quality in terms of yield, purity, and members present in
similar amounts. Notably, the library was prepared on a large scale (∼15 to 20 mg per member) and in a
time/cost efficient manner. The pooling approach facilitated synthesis and should also prove advantageous
in biological screening experiments.