Synthesis of (purin-6-yl)acetates and 6-(2-hydroxyethyl)purines via cross-couplings of 6-chloropurines with the Reformatsky reagent

Synthesis of 2,6‐Dialkyl(aryl)purine Nucleosides by Exploiting the Reactivity of Nebularine N1‐Oxide towards Grignard Reagents

“…Compound 4c was synthesized taking into account that nucleosides bearing hydroxyalkyl chains at the C6 purine position could be useful intermediates for further functionalization/conjugation. According to the literature, the introduction of a 2‐hydroxyethyl chain at the C6 purine position can be performed by a Reformatsky reaction followed by reduction of the acetate ester 15. Our method is generally applicable and allows for introduction of the suitable hydroxyalkyl chain using the Grignard reagents generated by the corresponding hydroxy‐protected bromoalcohol.…”

An Efficient Synthesis of 2‐Chloropyrimidines via Pd‐catalyzed Regioselective Dechlorination of 2,4‐Dichloropyrimidines in the Presence of NaHCO3

“…Of the many methods to build up complex pyrimidine containing molecules, cross-coupling reaction between a nucleophile and halopyrimidines is a very powerful synthetic approach. 1 Thus chloropyrimidines, including 2-chloro-pyrimidines, play an important role as a class of versatile building blocks. Among the reports for the synthesis of 2-chloropyrimidines, 2 its preparation from readily accessible 2,4-dichloropyrimidines through regioselective dechlorination is an attractive choice.…”

Synthesis of 6‐(4,5‐Dihydrofuran‐2‐yl)‐ and 6‐(Tetrahydrofuran‐2‐yl)purine Bases and Nucleosides

“…[8] In some cases, purines bearing functionalized carbon substituents at the 6-position have been prepared by the direct cross-coupling [9] of 6-halopurines with functionalized organometallics. This approach has been successfully used to synthesize 6-(hydroxymethyl)purines by the coupling of (acyloxymethyl)zinc iodides, [3] 6-(ethoxycarbonylmethyl)-purines by coupling with the Reformatsky reagent, [10] and purin-6-yl amino acids by coupling with protected amino acid organometallics. [11] Other types of substituents have been prepared by functional-group transformation [4,5,12] of 6-(hydroxymethyl)purines or by conjugate addition of nucleophiles to 6-ethynyl-and 6-vinylpurines.…”