Direct C–H Arylation of Purine on Solid Phase and Its Use for Chemical Libraries Synthesis

Abstract

C(8)-H direct arylation of purine derivatives immobilized on Wang resin is described. The purine skeleton was immobilized via C(6)-regioselective substitution of 2,6-dichloropurine with polymer-supported amines. After N(9)-alkylation with two different alkyl iodides and C(2) substitution with two selected amines, reaction conditions for C(8)-H arylation were developed and optimized. Various aryl bromides and aryl iodides were used for the reaction affording the target 2,6,8,9-tetrasubstituted purines in very good purity. The same reaction conditions were also applied for the synthesis of 2,6,8-trisubstituted purines, however, yields were lower. The methodology is applicable for high throughput synthesis of chemical libraries comprised of purine scaffold.

Microwave-assisted synthesis of C-8 aryl and heteroaryl inosines and determination of their inhibitory activities against Plasmodium falciparum purine nucleoside phosphorylase

“…Thus reaction of 2´,3´-Oisopropylideneinosine (1) with a variety of aryl iodides (3-iodoanisole, 4-iodotoluene, 4(3)trifluoromethylphenyl iodides) under microwave conditions (120 °C, 1h) using Cs 2 CO 3 , CuI, Pd(OAc) 2 and piperidine afforded the 8-arylinosines (4-7) in good yields. No significant differences were observed when employing electrondonating or electronwithdrawing groups at the aryl moiety, in agreement with that reported by other authors [4,20]. The reaction also took place when an aryl bromide was used (i.e., 4-bromoanisole) but the yield was significantly lower than that obtained with the corresponding aryl iodide.…”

Synthesis of Piperazinones, Piperazines, Tetrahydropyrazines, and Dihydropyrazinones from Polymer‐Supported Acyclic Intermediates via N‐Alkyl‐ and N‐Acyl­iminiums

“…Among the various methods for iminium ion synthesis, the condensation of secondary amides/amines with aldehydes/ketones is regarded as one of the most versatile 6,13–15. All polymer‐supported acyclic precursors were synthesized using standard solid‐phase chemistry16–21 and individual synthetic steps will be portrayed for each particular reaction sequence.…”

Biaryl Synthesis through Metal‐Catalyzed C–H Arylation

“…Zhang [113] reported ligand-free conditions under Cu nanoparticles, and Hlavác [114] demonstrated a direct arylation of purines using palladium and copper catalysts in solid phase.…”