A Novel Practical Synthesis of C‐2‐Arylpurines

Abstract

AbstractSuzuki–Miyaura cross‐coupling of halopurines with arylboronic acids would be one of the most efficient methods to synthesize C‐2‐arylpurines. However, as this approach implied some potential disadvantages, we needed to devise a more efficient process. Starting with 4‐amino‐2‐chloro‐5‐nitropyrimidine, readily prepared from 5‐nitrouracil, seemed to potentially obviate our concerns, and the applicability of the Suzuki–Miyaura coupling was examined in detail. Considerable competitive hydrolysis occurred simultaneously with the desired reaction under the aqueous conditions typically employed in the Suzuki–Miyaura protocol. Excellent yields were obtained with 1,1′‐bis(di‐tert‐butylphosphino)ferrocene (=D‐t‐BPF) under anhydrous conditions. Tolerance of various arylboronic acids was also found. Subsequent reduction with H2/Pd‐C of one of the coupling adducts, 4‐amino‐5‐nitro‐2‐phenylpyrimidine, gave the diamine, which was further condensed with activated acid derivatives to afford a wide variety of the 2‐phenylpurine derivatives in excellent yields.