Modification of Pyrrolo[2,3-d]pyrimidines by C-H Borylation Followed by Cross-Coupling or Other Transformations: Synthesis of 6,8-Disubstituted 7-Deazapurine Bases
Abstract
A general access to 4-substituted 6-arylpyrrolo[2,3-d]pyrimidine (6-substituted 8-aryl-7-deazapurine derivatives) was developed based on iridium-catalyzed C-H borylations of pyrrolo[2,3-d]pyrimidines at the 6-position followed by the Suzuki cross-coupling reactions or other functional group transformations of the boronates. Biologically relevant 6-arylpyrrolo[2,3-d]pyrimidin-4-amines (8-aryl-7-deazaadenines) and pyrrolo[2,3-d]pyrimidin-4-ones (-7-deazahypoxanthines) were synthesized starting from SEM-protected 4-methylsulfanyl- or 4-methoxypyrrolo[2,3-d]pyrimidine.
The one-pot borylation/Suzuki coupling reactions were followed either by demethylation and deprotection to yield deazahypoxanthine bases, or by oxidation of sulfide to sulfone, amination and deprotection to give deazaadenines. In addition, the boronate intermediates were converted into 6-halo- or 6-(trifluoromethyl)pyrrolo[2,3-d]pyrimidine (8-halo- or 8-trifluoromethyl-7-deazapurine) derivatives.