Several Pd‐catalyzed coupling reactions have been evaluated for the synthesis of 5‐substituted uracils. A convenient reaction, further developed by us, is the Suzuki Pd(0)‐catalyzed coupling between arylboronic acids and aryl bromides or iodides in weakly alkaline medium. However, all attempts to use 5‐bromo‐ or 5‐iodouracil as the aryl halide failed. On the other hand, couplings between 2,4‐di‐t‐butoxy‐5‐bromopyrimidine and various arylboronic acids were successful. In cases when the arylboronic acids were not available, it was better to reverse the coupling functionalities and use 2,4‐di‐t‐butoxy‐5‐pyrimidineboronic acid and arylbromides. A large number of 5‐aryluracils were prepared in this way. They were obtained in almost quantitative yields by dealkylation of the 5‐aryl‐2,4‐di‐t‐butoxypyrimidines. However, a great drawback of these procedures is the highly allergenic properties of 2,4‐dichloro‐5‐bromopyrimidine, which is an intermediate in the synthesis of 2,4‐di‐t‐butoxy‐5‐bromopyrimidine and 2,4‐di‐t‐butoxy‐5‐pyrimidineboronic acid. In order to avoid this intermediate the coupling between 5‐bromo‐2,4‐ditrimethylsilyloxypyrimidine and arylboronic acids were attempted but failed. Also attemptes to prepare 2,4‐di‐trimethylsilyloxy‐5‐pyrimidineboronic acid failed due to migration of a silyl group to the 5‐position upon halogen‐metal exchange. We therefore turned to the use of tin derivatives instead of boronic acids in the coupling reaction, which can be carried out under neutral conditions. Thus 5‐(1‐methyl‐2‐pyrrolyl)uracil, which could not be prepared from 2‐bromo‐1‐methylpyrrole and 2,4‐di‐t‐butoxy‐5‐pyrimidineboronic acid was obtained through the Pd(0)‐catalyzed coupling of 1‐methyl‐2‐trimethylstannylpyrrole and 2,4‐di‐t‐butoxy‐5‐bromopyrimidine followed by dealkylation. However, the great advantage with the tin derivatives was that 5‐bromo‐2,4‐ditrimethylsilyloxypyrimidine could be used in the coupling with aryltin derivatives giving 5‐aryluracils in reasonable yields. We also tried to use unprotected 5‐halouracils in the coupling reactions. We were unsuccessful with the 5‐bromo derivative. However, with 5‐iodouracil coupling was achieved in some cases.

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