Benzylamine → 2-Chloro-6-benzylamino-9-(2-propynyl)purine

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Reaction Steps

In one example of the application, a triazole and its fluorinated derivatives can be prepared by a Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction of the corresponding alkyne and azide substrates. As shown below in Scheme 1, synthesis can begin with the reaction of 2,6-dichloropurine (Compound 3) with benzylamine (a) as described, for example, by Oumata, N. et al., Org. Process Res. Dev. 13:641-644 (2009). Using the conditions set forth in the Example below, the reaction can be completed in about 15 minutes at about 60° C. 2-chloro-6-benzylaminopurine (Compound 4) can be propargylated using propargyl bromide in DMSO under mild conditions to yield 2-chloro-6-benzylamino-9-(2-propynyl) purine (Compound 5). The Cu(I)-catalyzed azide-alyne click reaction (as described, for example, by Amblard, F. et al., Chem. Rev. 109:4207-4220, 2009) of 2-chloro-6-benzylamino-9-(2-propynyl) purine (Compound 5) with fluorinated benzyl azides (which can be prepared in situ from their corresponding benzyl bromides) can then yield 1,4-disubstituted triazoles or, more specifically, 2-chloro-6-benzylamino-9-[1-(2-fluorobenzyl)-1H-1,2,3-triazol-4-yl-methyl]purine (Compound 7), 2-chloro-6-benzylamino-9-[1-(2,6-difluorobenzyl)-1H-1,2,3-triazol-4-yl-methyl]purine (Compound 8), and 2-chloro-6-benzylamino-9-[1-(pentafluorobenzyl)-1H-1,2,3-triazol-4-yl-methyl]purine (Compound 9).

Provenance & Evidence