ChemInform Abstract: New 5‐Alkoxypyrimidine Derivatives from β‐Alkoxy β‐Keto Enamides and Ammonium Salts.

Abstract

A series of highly substituted β-alkoxy β-keto enamides were prepared by a multi-component reaction combining lithiated alkoxyallenes, nitriles and carboxylic acids. Apt conditions were developed for their conversion into 5-alkoxypyrimidine derivatives. This synthesis is highly flexible with respect to the substitution pattern at C-2 and C-4 of the pyrimidine core. The corresponding pyrimidin-5-yl nonaflates allowed subsequent transformations at C-5 by palladium-catalyzed couplings such as Sonogashira and Suzuki reactions. The Sonogashira coupling of a pyrimidinyl alkyne with a pyridinyl nonaflate and a subsequent cyclization led to an efficient access to pyrimidinyl-substituted furo[2,3-c]pyridine derivatives. The C-6 methyl group which is present in all of the prepared pyrimidines can easily be converted into formyl, carboxylic or alkynyl moieties which allow the synthesis of additional pyrimidine derivatives.