Grup d'Enginyeria Molecular, Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain.
Mol Divers. 2012 Nov;16(4):639-49. doi: 10.1007/s11030-012-9398-6. Epub 2012 Oct 10.
A practical protocol was developed for the synthesis of 2-arylamino substituted 4-amino-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones from α,β-unsaturated esters, malononitrile, and an aryl substituted guanidine via the corresponding 3-aryl-3,4,5,6- tetrahydropyrido[2,3-d]pyrimidin-7(8H)-ones. Such compounds are formed upon treatment of 2-methoxy-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles with an aryl substituted guanidine in 1,4-dioxane and are converted to the desired 4-aminopyridopyrimidines with NaOMe/MeOH through a Dimroth rearrangement. The overall yields of this three-step protocol are, generally speaking, higher than the multicomponent reaction, previously developed by our group, between an α,β-unsaturated ester, malononitrile, and an aryl substituted guanidine.
开发了一种实用的方案，用于通过α，β-不饱和酯、丙二腈和芳基取代胍，从相应的 3-芳基-3,4,5,6-四氢吡啶并[2,3-d]嘧啶-7(8H)-酮合成2-芳胺取代的 4-氨基-5,6-二氢吡啶并[2,3-d]嘧啶-7(8H)-酮。这些化合物是通过将 2-甲氧基-6-氧代-1,4,5,6-四氢吡啶-3-甲腈与芳基取代胍在 1,4-二氧六环中处理而形成的，并通过 Dimroth 重排，用 NaOMe/MeOH 将其转化为所需的 4-氨基吡啶并嘧啶。总体而言，三步方案的总收率高于我们小组之前开发的α，β-不饱和酯、丙二腈和芳基取代胍之间的多组分反应。
