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

Beteiligte Stoffe

Reaktionsschritte

The title compound was prepared according to method A as described in Example 1 by reacting 3-[(R)-2-amino-1-propylthio]-4-methyl-1,2,4-triazole 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 3-mercapto-4-methyl-1,2,4-triazole (2.3 g, 20 mmol) followed by acidic hydrolysis] (0.56 g, 2.2 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (1.0 g, 2.2 mmol), followed by deacylation of the purified 2',3',5'-tri-O-acetyl-2-chloro-N-[(R)-1-(4-methyl-1,2,4-triazol-3-yl)thio-2-propyl]adenosine using sodium methoxide in methanol to provide the title 2-chloro-N[(R)-1-(4-methyl-1,2,4-triazol-3-yl)thio-2-propyl]adenosine (0.17 g, 17%) as a foam after column chromatography. 1H NMR (DMSO-d6) δ 1.24 (3H, d, --CHCH3), 3.56, 3.67 (2H, ABX, 5'a and H-5'b), 3.95 (1H, q, H-4), 4.14 (1H, br q, H-3'), 4.15 -4.42 (2H, m, --CH2S--), 4.52 (1H, br q, H-2'), 4.80 (1H, m, --CHCH3), 5.07 (1H, br, 5'-OH), 5.22, 5.50 (2H, 2 br, 2'- and 3'-OH), 5.82 (1H, d, H-1'), 8.33 (1H, d,-NH), 8.39, 8.41 (2H, 2s, H-2 and Ar-H). HPLC retention time 7.79 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].

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