2,6-Dichloropurine

2,6-Dichloropurine is an important pharmaceutical intermediate. It is widely used in the preparation of purine nucleosides and purine nucleotides^[1].

white to light yellow crystal powder

2,6-Dichloropurine is used in the synthesis of 2,6-diamino-substituted purine derivatives as potential cardiomyogenesis inducing agents.

Suzuki-Miyaura cross-coupling between halopurines and arylboronic acids in water-acetonitrile.1

Journal of the American Chemical Society, 80, p. 404, 1958 DOI: 10.1021/ja01535a040

2,6-Dichloropurine is prepared in two main ways:
(1) By chlorination of the purine ring structure, e.g., chlorination of xanthine (2,6-dihydroxypurine) with pyrophosphoryl chloride at high temperatures in sealed tubes in the presence of a phase-transfer catalyst or with phosphorus oxychloride under reflux, and chlorination of 6-chloropurine, hypoxanthine, or their N-oxides with phosphorus oxychloride, and chlorination with chlorine gas at low temperatures. Chlorination of 2,6-dithiopurine.
(2) The purine ring is constructed using barbituric acid derivatives or 2,4-dichloro-5,6-diaminopyridine as starting materials. However, both methods are not very suitable for industrial production.
The industrial preparation of 2,6-dichloropurine involves the direct chlorination of xanthine with phosphorus trichloride and a weakly nucleophilic organic base (e.g., amidine, guanidine base, or proton sponge)^[1]. The reaction process is shown below:

It can be recrystallised from 150 parts of boiling H2O and dried at 100o to constant weight. It is soluble in EtOAc. The HgCl2 salt separates from EtOH solution. UV: max 275nm ( 8.9K) at pH 1; and 280nm ( 8.5K) at pH 11 [Elion & Hitchings J Am Chem Soc 78 3508 1956, Schaeffer & Thomas J Am Chem Soc 80 3738 1958, Beaman & Robins J Appl Chem (London) 12 432 1962, Montgomery J Am Chem Soc 78 1928 1956]. [Beilstein 26 III/IV 1747.]

[1] QI ZENG. Facile and Practical Synthesis of 2,6-Dichloropurine[J]. Organic Process Research & Development, 2004, 8 6: 962-963. DOI:10.1021/op049878r.