2,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purine → N-[(R)-1-(6-amino2-benzothiazolyl)thio-2-propyl]-2chloroadenosine

Participants

Reaction Steps

The title compound was prepared according to general method A as described above in Example 1 by reacting 6-amino-2-[(R)-2-aminopropyl-1-propylthio]benzothiazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1 using 2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol (13.1 g, 75 mmol) and 6-amino-2-mercaptobenzothiazole (13.7 g, 75 mmol) followed by acidic hydrolysis]) (2.51 g, 7.2 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (2.68 g, 6.0 mmol), followed by deacylation of the purified 2',3',5'-tri-O-acetyl-N-[(R)-1-(6-amino-2-benzothiazolyl)thio-2-propyl]-2-chloroadenosine in methanolic ammonia (200 ml) (previously saturated at -10° C.) to provide the title N-[(R)-1-(6-amino2-benzothiazolyl)thio-2-propyl]-2chloroadenosine (1.97 g, 63%) as a foam (following column chromatography), 1H NMR (DMSO-d6) δ 1.36 (3H, d, --CHCH3), 3,50-3.71 (4H, m, H-5'a and H-5'b and --CH2 --), 3.95 (1H, d, H-4'), 4.14 (1H, d, H-3'), 4.53 (1H, q, H-2'), 4.63 (1H, m, --CH), 5.08 (1H, t, 5'-OH), 5.22, 5.50 (2H, 2d, 2'- and 3'-OH), 5.83 (1H, d, H-1'), 6.71, 6.99, 7.53 (3H, 3d, Ar-H), 8.41 (1H, s, H-8), 8.52 (1H, d, N--H). HPLC retention time 10.29 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].

Provenance & Evidence