Study of Direct N7 Regioselective tert-Alkylation of 6-Substituted Purines and Their Modification at Position C6 through O, S, N, and C Substituents

TL;DR

Scientists developed a new method to selectively attach tert-alkyl groups to specific positions in purine compounds, which could lead to new biologically active molecules.

Contribution

A novel regioselective method for N7 tert-alkylation of 6-substituted purines is introduced, enabling new purine transformations.

Findings

A method using N-trimethylsilylated purines and SnCl4 catalyst successfully introduces tert-alkyl groups at the N7 position.

The stability of tert-butyl groups at N7 was confirmed through model reactions, leading to new 6,7-disubstituted purine derivatives.

The approach allows preparation of 7-(tert-butyl)-6-chloropurine, a compound useful for further chemical transformations.

Abstract

A new N7 direct regioselective
method
allowing the introduction of tert-alkyl groups into
appropriate 6-substituted purine derivatives is developed. This method
is based on a reaction of N-trimethylsilylated purines
with a tert-alkyl halide using SnCl4 as
a catalyst. In this work, we study the structure and optimal reaction
conditions leading to the N7 isomer and
in some cases also to the N9 isomer. The
main goal is devoted to preparing 7-(tert-butyl)-6-chloropurine
as a suitable compound for other purine transformations. The stability
of the tert-butyl group at the N7 position is tested for classic model reactions, leading
to the preparation of new 6,7-disubstituted purine derivatives, which
is also interesting from the point of view of possible biological
activity.

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