A Novel Practical Synthesis of C‐2‐Arylpurines

Abstract

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 ( ¼ 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.

N4,N6-Dimethyl-N4,N6-diphenylpyrimidine-4,5,6-triamine

“…Pyrimidine triamines not only exhibit a wide range of biological activities (Barillari et al, 2001), but also are important intermediate products (Koppel & Robins, 1958;Itoh et al, 2004). Here, the crystal structure of N 4 ,N 6 -dimethyl-N 4 ,N 6 -diphenylpyrimidine-4,5,6-triamine is reported.…”

“…For applications and the biological activity of pyrimidine triamines, see: Barillari et al (2001); Itoh et al (2004); Koppel & Robins (1958). Data collection: PROCESS-AUTO (Rigaku, 1998); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku/ MSC, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2000); software used to prepare material for publication: SHELXL97.…”

N4,N6-Dimethyl-5-nitro-N4,N6-diphenylpyrimidine-4,6-diamine

“…Pyrimidine diamines, important intermediate products (Koppel et al, 1958;Itoh et al, 2004;Che et al, 2008;Shi et al, 2011), exhibit a wide range of biological activities (Barillari et al, 2001). Here, the crystal structure of N 4 ,N 6 -dimethyl-5nitro-N 4 , N 6 -diphenylpyrimidine-4,6-diamine is determined by X-ray single crystal diffraction.…”

Tetraphosphine/palladium‐catalyzed Suzuki–Miyaura coupling of heteroaryl halides with 3‐pyridine‐ and 3‐thiopheneboronic acid: an efficient catalyst for the formation of biheteroaryls

“…Chelating phosphine ligands are applied to the synthesis of biheteroaryls as well . However, the inactive pyridineboronic acids are less involved .…”

“…Chelating phosphine ligands are applied to the synthesis of biheteroaryls as well. [34][35][36] However, the inactive pyridineboronic acids are less involved. [37][38][39] To the best of our knowledge, cis,cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane (Tedicyp) is the only multidentate phosphine ligand participating in the formation of biheteroaryls.…”