Direct reductive amination of functionalized aldehydes with aniline derivatives of purines and 7-deazapurines

• Published in: Organic & biomolecular chemistry 2023-07, Vol.21 (26), p.5457-5468
• Main Authors: Orduña, José-María, del Río, Natalia, Pérez-Pérez, María-Jesús
• Format: Article
• Language: English
• Subjects: Adenine; Aldehydes; Alkylation; Amination; Aniline; Chemical reduction; Direct reduction; Evaporation; Protecting groups; Purines; Reagents; Reducing agents
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d3ob00822c

Reductive amination plays a key role in the medicinal chemistry toolbox since it allows the mono alkylation of an amine or aniline. In this work, reductive amination of functionalized aldehydes with aniline derivatives of adenine and closely related 7-deazapurines has been successfully performed using H-cube technology so that imine formation and its reduction are performed " in situ ". The set-up procedure surmounts some of the drawbacks of "in batch" protocols by avoiding the handling of reductant reagents, long reaction times and tedious work-ups. The here described procedure allows a high conversion into the reductive amination products together with an easy work-up by just evaporation. More interestingly, this set-up does not require the presence of acids so that acid-sensitive protecting groups can be present both at the aldehyde and at the heterocycle. Monosubstituted aniline derivatives of (7-deaza)purines have been efficiently synthesized through reductive amination of diversely functionalized aldehydes, including N -Boc protected derivatives.