Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 1: pyrido[2,3‐ b ]pyrazines

BACKGROUND: The excellent fungicidal activity of [1,2,4]triazolo[1,5‐ a ]pyrimidines suggested the search for further analogues with improved properties. RESULTS: A series of novel trisubstituted pyrido[2,3‐ b ]pyrazines has been designed and prepared as 6,6‐biheterocyclic analogues of related 5,6‐bicyclic [1,2,4]triazolo[1,5‐ a ]pyrimidines. Their fungicidal activity was evaluated against the plant pathogens Puccinia recondita Rob. ex Desm. f. sp. tritici (Eriks.) CO Johnston (wheat brown rust), Mycosphaerella graminicola (Fuckel) Schroter ( Septoria tritici Rob., leaf spot of wheat) and Magnaporthe grisea (Hebert) Barr ( Pyricularia oryzae Cav., rice blast). Structure–activity relationship studies revealed the advantage of a fluoro substituent in position 6 and of a secondary amine in position 8. CONCLUSION: 8‐Amino‐7‐aryl‐6‐halogen‐substituted pyrido[2,3‐ b ]pyrazines have been prepared as 6,6‐biheterocyclic analogues of similarly substituted triazolopyrimidine fungicides. A concise four‐step synthesis route has been worked out to prepare these novel compounds from commercially available starting materials. [( R )‐(1,2‐Dimethylpropyl)]‐[6‐fluoro‐7‐(2,4,6‐trifluorophenyl)pyrido[2,3‐ b ]pyrazin‐8‐yl]amine showed excellent activity against three economically important phytopathogens. Copyright © 2009 Society of Chemical Industry