Synthesis of a 2, 4, 8-trisubstituted pyrimidino[5, 4-d]pyrimidine library via sequential SNAr reactions on solid-phase.
A solid-phase synthesis of 2, 4, 8-substituted pyrimidino[5, 4-d]pyrimidines involving three controlled S(N)Ar reactions has been developed. Exploration of different heterocyclic starting materials and resin-bound intermediates is highlighted. The preferred method starts with the treatment of resin-bound anilines with 2, 4, 8-trichloropyrimidino[5, 4-d]pyrimidine. This intermediate is subsequently treated with various amines in two steps to yield the final products. The scope of each diversity step was determined and a library of 16, 000 compounds was synthesized.
Drug Discovery, Johnson & Johnson Pharmaceutical Research and Develoment, L.L.C., 8 Clarke Dr., Cranbury, NJ 08512, USA. mplayer@prdus.jnj.com
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El-Araby
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Pottorf
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D020650:Combinatorial Chemistry Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011743:Pyrimidines / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D011743:Pyrimidines