2,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purine → N[(R)-1-(6-ethoxy-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]-6-ethoxybenzothiazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1 using 2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol (3.5 g, 20 mmol) and 6-ethoxy-2-mercaptobenzothiazole (4.23 g, 20 mmol) followed by acidic hydrolysis] (3.8 g, 11.1 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (1.1 g, 2.5 mmol), followed by deacylation of the purified 2',3',5'-tri-O-acetyl-2 -chloro-N-[(R)-1-(6-ethoxy-2-benzothiazolyl)thio-2-propyl]adenosine using sodium methoxide in methanol to provide the title N[(R)-1-(6-ethoxy-2-benzothiazolyl)thio-2-propyl]-2-chloroadenosine (0.22 g, 17%) as a foam (following column chromatography), 1H NMR (DMSO-d6) δ 1.32-1.40 (6H, m, --CH2CH3 and --CHCH3), 3.44-3.81 (4H, m, H-5'a and H-5'b and --CH2 --), 3.97 (1H, d, H-4'), 4.08 (2H, q, --CH2CH3), 4.14 (1H, d, H-3'), 4.53 (1H, q, H-2'), 4.68 (1H, m, --CH), 5.09 (1H, t, 5'-OH), 5.23, 5.51 (2H, 2d, 2'- and 3'-OH), 5.83 (1H, d, H-1'), 7.06, 7.57, 7.74 (3H, 3d, Ar-H), 8.42 (1H, s, H-8), 8.53 (1H, d, N--H). HPLC retention time 22.4 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].

Provenance & Evidence