Microwave-Assisted Synthesis of 9-Arylpurines

Microwaves in Heterocyclic Chemistry

“…The same group subsequently confirmed that this methodology could be extended to the synthesis of novel 6-[N,N -bis(2-hydroxyethyl)amino]purine nucleosides by reaction of diethanolamine with various 6-chloropurines (100 • C, 10 min) in water [149]. (16.25) Nucleophilic aromatic substitution at the C-6 position of 6-chloropurine derivatives under microwave irradiation has been also confirmed with other N-nucleophiles such as methylpiperazine, benzylamine, and N,N-dimethylethylenediamine (120 • C, 10-20 min,NN-diisopropylethylamine in 2-propanol solution) by Pérez-Pérez and co-workers [150]. Marine sponges have been proved to be a source of biologically active alkaloids and their metabolites.…”

Comprehensive Survey of Chemical Libraries for Drug Discovery and Chemical Biology: 2008

“…However, challenging multistep synthesis of reactive intermediates and harsh reaction conditions limit their general utility, particularly for the preparation of pyrimidine-based arrays. The initial 3-CR was conducted by simply heating enamines 158 with 3 equiv of orthoester and 2 equiv of NH 4 OAc in toluene at 100 °C for 20 h. Optimized reaction conditions included the addition of 0.1 equiv of ZnCl 2 which improved the overall yield (>70%), accelerated reaction time and enhanced the range of substrates. Non-commercially available enamines were prepared in high yield (>90%) by the addition of electron-withdrawing stabilized carbon nucleophiles to arylnitriles.…”

“…Library synthesis commenced by the addition of Grignard intermediate 81, derived from m-and p-1,3-dioxane-subsituted bromobenzene to N-vinyl pyrrolidinone 82 affording 2-pyrrolines 83 (23-29% yields). These cyclic imines were reduced to 84 with NaBH 4 and then coupled to phenol-protected benzoic acid 85. Deprotection of the phenol groups with either TFA or HCl resulted in aldehydes 86 that were subjected to reductive amination with ca.…”

“…The pyrrolidine derivative 136 was then converted to the bridge bicyclic scaffold 140 in 5 steps, i.e. a) protection of the NH functionality of 136 as the N-Fmoc derivative, b) deprotection of the allyl ester functionality by treatment with Pd(PPh 3 ) 4 , c) conversion of the resulting carboxylic acid to the corresponding primary alcohol, d) activation of the resulting alcohol with mesyl chloride followed by formation of the pyridone ring via intramolecular cyclization, and e) conversion of the 1,3-dioxolane, 2,2-dimethyl functionality to the corresponding primary alcohol according to a 3-step sequence. The tricyclic synthon 141 was prepared from phosphonate 143 via a synthetic sequence similar to the one described for the preparation of 140.…”

Solid-Phase Synthesis of 1,3,7,8-Tetrasubstituted Xanthine Derivatives on Traceless Solid Support

“…Thus, they serve as attractive scaffolds for combinatorial library construction via solution- and solid-phase synthesis. The solid-phase synthetic approaches for xanthines − and their relative derivatives, such as purines, , hypoxanthines, and pyrrolopyrimidines, , have been well-described. However, to the best of our knowledge, there are only two reports that describe the synthesis of 1,3,7,8-tetrasubstituted xanthine 1 (see Figure ) on solid support. , Although the known methods for the synthesis of xanthines 1 are very useful, a C8 substituent was introduced at the early stage in the solid-phase synthesis.…”