9-benzyl-2,6-dichloro-9H-purine

27.1 Preparation of 9-benzyl-2, 6-dich.oro-9H-purine Potassium carbonate (2.07 g, 15 mmol) was added to a solution of 2, 6-dichloro-9H- purine (945 mg, 5.0 mmol) in dimethylformamide (20 ml) and the mixture stirred at ambient temperature for 30 minutes. Benzyl bromide (1.2 ml, 10 mmol) was added and the mixture stirred overnight. Water was added and the resulting mixture extracted with ethyl acetate. The comined organic extracts were washed with water and brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by automated flash chromatography (Presearch Combiflash Rf) on silica, with ethyl acetate in hexane ( 0percent to 80percent gradient) as eluent, to provide 9-benzyl- 2, 6-dichloro-9H-purine as a white solid (876 mg, 94percent).Characterising data for the compound are as follows:1H NMR (400 MHz, CDCI2, 6-Dichloro-9H-purine (10.9 g, 60 mmol; purchased from Aldrich Chemical Co.) was dissolved in 200 ml_ dimethylformamide (DMF) and potassium carbonate (31.9 g, 230 mmol) was added. Benzyl bromide (13.7 ml_, 120 mmol) was added in portions and the whole stirred at room temperature under nitrogen for 16 hours. The mixture was filtered through a short plug of Arbocel.(R). and the filtrate was evaporated in vacuo To a stirred solution of 2, 6-dichloropurine (5.30 mmol, 1 eq) in 10 ml anhydrous DMSO at room temperature was added anhydrous potassium carbonate (6.34 mmol, 1.2 eq) and benzyl bromide (6.34 mmol, 1.2 eq). The reaction mixture was maintained at this temperature for 20 h. The reaction can be monitored using either TLC or LC/MS. The reaction mixture was poured into a beaker containing ice- cold water. The aqueous layer was acidified to pH 5-6. Extraction of the aqueous layer, using 3x75 ml portions of ethyl acetate, afforded the crude product. This was purified on the silica gel column (10-70percent ethyl acetate in petroleum ether, step- gradient), to give the desired compound in a yield of 56percent.General procedure: 2, 6-Dichloro-9H-purine (15.8 mmol), an appropriate alcohol(31.7 mmol), and triphenylphosphine (19.0 mmol) were dissolved in dry tetrahydrofuran (100 mL) and cooled to 0°C. Diisopropyl azodicarboxylate (19.0 mmol) was added dropwise to the stirred solution under an argon atmosphere, and the temperature was kept between 0 and 20°C. The reaction mixture was stirred underan argon at mosphere at 20°C for a further 2–4 h. The reaction was monitored by TLC until completion. The reaction mixture was then evaporated under reduced pressure, and the residue was dissolvedin boiling toluene (100 mL). After cooling to room temperature, the solution was inoculated with a small amount of triphenylphosphineoxide and the solution was kept at 4°C for 24 h. The triphenylphosphineoxide was then filtered off and the filtrate was evaporated under reduced pressure. The residue was crystallized from ethanol or purified by column chromatography on silica (petroleumether: ethyl acetate, 2:1) to afford the pure product.2, 6-Dichloro-9H-purine (10.9g, δOmmol; purchased from Aldrich Chemical Co.) was dissolved in DMF (20OmL) and potassium carbonate (31.9g, 230mmol) added. Benzyl bromide (13.7ml_, 120mmol) was added in portions and the whole stirred at rt under nitrogen for 16h. The mixture was filtered through a short plug of Arbocel.(R). and the filtrate was evaporated in vacuo to give a yellow oil of the N7- (more polar) and N9-benzyl (less polar) purines. This oil was purified by silica gel chromatography using 1 :2:10 EtOAc:acetone:hexane as eluent to give the title compound as a white solid (9.1 g, 57percent).9-Benzyl-2, 6-dichloro-9H-purine and 7-benzyl-2, 6-dichloro-7H-purine were synthesized according to a method described in the literature: G. Langli; L. L. Gundersen and F. Rise, Tetrahedron 1996, 52 (15), 5625-5638. 2, 6-Dichloropurine (18.9 g, 0.10 mol) and potassium carbonate (41.5 g, 0.30 mol) were added to DMF (500 mL) and the mixture was stirred under nitrogen atmosphere for 20 min. Benzylchloride (17.5 mL, 0.15 mol) was added and the mixture was further stirred for 24 hrs. After filtration, DMF was evaporated under reduced pressure, and the obtained reaction mixture was separated and purified by silica gel column chromatography to give 9-benzyl-2, 6-dichloro-9H-purine (18.1 g, 64.8 mmol, yield 65percent) and 7-benzyl-2, 6-dichloro-7H-purine (2.79 g, 10.0 mmol, yield 10percent).

Molecular Weight:279.12
XLogP3:4
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:278.0126017
Monoisotopic Mass:278.0126017
Topological Polar Surface Area:43.6
Heavy Atom Count:18
Complexity:285
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes