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

Participants

Reaction Steps

The title compound was prepared according to method A as described in Example 1 by reacting 2-[(R)-2-amino-1-propylthio]-4-phenylthiazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1 using 2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol (2.72 g, 15.5 mmol) and 2-mercapto-4-phenylthiazole (3.0 g, 15.5 mmol) followed by acidic hydrolysis] (1.15 g, 4.0 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (1.5 g, 3.35 mmol), followed by deacylation of the purified 2',3',5'-tri-O-acetyl-2-chloro-N-[(R)-1-(4-phenyl-2-thiazolyl)thio-2-propyl]adenosine using sodium methoxide in methanol to provide the title 2-chloro-N-[(R)-1-(4-phenyl- 2-thiazolyl)thio-2-propyl]adenosine (0.36 g, 20%) as a foam after column chromatography. 1H NMR (DMSO-d6) δ 1.37 (3H, d, --CHCH3), 3.4-3.73 (2H, m, 5'a and H-5'b and --CH2 --S--), 3.94 (1H, q, H-4), 4.13 (1H, q, H-3'), 4.52 (1H, q, H-2'), 4.71 (1H, m, --CHCH3), 5.06 (1H, t, 5'-OH), 5.22, 5.50 (2H, 2d, 2'- and 3'-OH), 5.83 (1H, d, H-1'), 7.33, 7.42 (3H, dt, Ar-H), 7.91 (2H, d, Ar-H), 8.41 (1H, s, H-2), 8.47 (1H, d, --NH). HPLC retention time 18.99 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].

Provenance & Evidence