Highly Efficient and Broad-Scope Protocol for the Preparation of 7-Substituted 6-Halopurines via N ⁹-Boc-Protected 7,8-Dihydropurines

Abstract

9-Boc-6-chloropurine, which can be obtained in high yield, is nearly quantitatively reduced with the THF˙BH₃ complex. The obtained 9-Boc-7,8-dihydropurine derivative is more stable compared to the corresponding 9-tritylpurine and can be smoothly N⁷-alkylated, acylated, or it can serve as an N-nucleophile in conjugate additions. Deprotection with trifluoroacetic acid followed by MnO₂ oxidation affords the N⁷-substituted purines in high yields. The whole sequence of alkylation, deprotection, and oxidation can be done with crude intermediates using chromatography only for the purification of the final N⁷-substituted purine.

alkylation - acylation - Michael addition - nucleobases - reduction

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