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

Participants

Reaction Steps

N-[3-(2-Benzothiazolyl)thio-1,1,1-trifluoro-2-propyl]-2-chloroadenosine was prepared according to general method A as described in Example 1 by reacting 2-[(R)-2-amino-1,1,1 trifluoro-3-propylthio]benzothiazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1 using the above 2-(N-tert-butyloxycarbonyl)amino-1,1,1-trifluoro-3-propanol and 2-mercaptobenzothiazole followed by acidic hydrolysis] (0.13 g, 0.47 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (0.21 g, 0.45 mmol). Debenzoylation of the purified 2',3',5'-tri-O-acetyl-N-[3-(2-benzothiazolyl)thio-1,1,1-trifluoro-2-propyl]-2-chloroadenosine in methanolic ammonia (20 ml) (previously saturated at -10° C.) provided the title N-[3-(2-benzothiazolyl)thio-1,1,1-trifluoro-2-propyl]-2-chloroadenosine (0.12 g, 45%) (following column chromatography) [a mixture of (R)- & (S)- diastereoisomers]; 1H NMR (DMSO-d6) δ3.39-3.49 (1H, m, --CH), 3.58, 3.68 (2H, ABX, H-5'a and H-5'b), 3.98 (1H, q, H-4'), 4.11-4.18 (2H, m, H-3' and --CH--), 4.47-4.56 (1H, m, H-2'), 5.08 (1H, m, 5'-OH), 5.18-5.28 (1H, m, --CHCH2 --), 5.27, 5.57 (2H, 2d, 2'- and 3'-OH), 5.94 (1H, d, H-1'), 7.08, 7.22, 7.30 (3H, 3 t, Ar--H), 7.71 (1H, d, Ar--H), 8.75 (1H, s, H-8), 8.79 (1H, d, N--H).

Provenance & Evidence