2,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purine → N-[(R)-1-(5-chloro-2-benzothiazolyl)thio-2-propyl]2-chloroadenosine

Participants

Reaction Steps

The title compound was prepared according to general method A as described above in Example 1 by reacting 2-[(R)-2-amino-1-propylthio]-5-chlorobenzothiazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1]with 2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol (1.75 g, 10 mmol) and 5-chloro-2-mercaptobenzothiazole (2.02 g, 10 mmol) followed by acidic hydrolysis] (0.5 g, 1.5 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (0.54 g, 1.2 mmol), followed by deacylation of the purified 2',3',5'-tri-O-acetyl-2-chloro-N-[(R)-1-(5-chloro-2-benzothiazolyl)thio-2-propyl]adenosine using sodium methoxide in methanol to provide the title N-[(R)-1-(5-chloro-2-benzothiazolyl)thio-2-propyl]2-chloroadenosine (0.30 g, 46%) as a solid, mp 145 ° C. (following column chromatography), 1H NMR (DMSO-d6) δ 1.39 (3H, d, --CHCH3), 3.45-3.78 (4H, m, H-5'a and H-5'b and --CH2 --), 3.96 (1H, q, H-4'), 4.14 (1H, t, H-3'), 4.52 (1H, t, H-2'), 4.72 (1H, m,-CH), 5.84 (1H, d, H-1'), 7.41 (1H, dd, Ar-H), 7.94 (1H, s, Ar-H), 8.02 (1H, dd, Ar-H), 8.42 (1H, s, H-8), 8.52 (1H, d, N--H). HPLC retention time 23.58 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].

Provenance & Evidence