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A Novel Practical Synthesis of C ‐2‐Arylpurines
Author(s) -
Itoh Takahiro,
Sato Kimihiko,
Mase Toshiaki
Publication year - 2004
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200404159
Subject(s) - chemistry , anhydrous , ferrocene , adduct , hydrolysis , diamine , combinatorial chemistry , aqueous solution , nitro , reaction conditions , organic chemistry , catalysis , alkyl , electrode , electrochemistry
Suzuki–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 H 2 /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.