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New 5‐Alkoxypyrimidine Derivatives from β‐Alkoxy β‐Keto Enamides and Ammonium Salts
Author(s) -
Lechel Tilman,
Reissig HansUlrich
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201000056
Subject(s) - chemistry , sonogashira coupling , pyrimidine , alkyne , pyridine , alkoxy group , combinatorial chemistry , palladium , medicinal chemistry , catalysis , organic chemistry , stereochemistry , alkyl
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.