2,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purine → 2-chloro-N-{(R)-1-[5-phenyl-(1,2,4-triazol-3-yl)]thio-2-propyl}adenosine

Participants

Reaction Steps

The title compound was prepared according to method A as described in Example 1 by reacting 3-[(R)-2-amino-1-propylthio]-5-phenyl-1,2,4-triazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1 using 2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol (2.0 g, 11.4 mmol) and 3-mercapto-5-phenyl-1,2,4-triazole (2.0 g, 11 mmol) followed by acidic hydrolysis] (0.50 g, 1.8 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (0.75 g, 1.7 mmol), followed by deacylation of the purified 2',3',5'-tri-O-acetyl-2-chloro-N-{(R)-1-[5-phenyl-(1,2,4-triazol-3-yl)]thio-2-propyl}adenosine using sodium methoxide in methanol to provide the title 2-chloro-N-{(R)-1-[5-phenyl-(1,2,4-triazol-3-yl)]thio-2-propyl}adenosine (0.21 g, 24%) as a foam after column chromatography. 1H NMR (DMSO-d6)5 1.34 (3H, d, --CHCH3), 3.37-3.70 (4H, m, --CH2 --, H-5'a and H-5'b), 3.95 (1H, q, H-4), 4.13 (1H, t, H-3'), 4.53 (1H, t, H-2'), 4.59-4.69 (1H, m, --CHCH3), 5.07 (1H, t, 5'-OH), 5.22, 5.50 (2H, 2d, 2'- and 3'-OH), 5.83 (1H, d, H-1'), 7.43-7.54 (3H, m, Ar-H), 7.90, 8.0 (2H, m, Ar-H), 8.40 (1H, s, H-2). 8.42 (1H, d, --NH), HPLC retention time 14.5 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].

Provenance & Evidence