Methanol → HCID 86751192, compound

Temperature

45 °C

2-Amino-6-(cycloropylmethoxy)-9H-purine (0.53 g, 2.6 mmoles) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 mmoles) were suspended in 50 ml, 10 mM potassium phosphate buffer, pH 7.0, containing 0.04% potassium azide. Purine nucleoside phosphorylase (1120 I.U.) and thymidine phosphorylase (10,000 I.U.) (Krenitsky et al., Biochemistry, 20, 3615 (1981) and U.S. Pat. No. 4,381,344) immobilized on DEAE cellulose was added to the reaction and the suspension was stirred at 45° C. After 4 days, 182 ml MeOH was added to the reaction. The reaction was applied to a column containing AG1-X2 (OH-- form, 2.5×10 cm) and eluted with MeOH. Fractions containing product were pooled, concentrated, and flash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (9:1). Solvent was removed and lyophilization yielded 0.414 g of 2-amino-6-cyclopropylmethoxy)-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-9H-purine (57%): mp 80°-81° C.; TLC Rf 0.75 (silica gel, MeCN:15N NH4OH:H2O/85:5:10); [α]D20 -19.0 (c=0.5, DMF);UV λmax (ε×10-3) at pH 7, 247 (9.7); at pH 13, 247 (9.3);1H NMR (200 MHz, DMSO-d6) δ8.13 (s, 1H, H8), 6.47 (b, 2H, NH2), 6.27 (dd, 1H, H1', J=9.3 Hz, J=5.6 Hz), 5.43 (dd, 1H, H3', J=54 Hz, J=4.2 Hz), 5.24 (t, 1H, OH5'J=5.6 Hz), 4.26 (d, 2H, OCH2, J=7.2 Hz), 4.11-4.27 (m, 1H, H4'), 3.59 (t, 2H, H5' and H5", J=5.2 Hz), and 2.62-3.01 (m, 2H, H2' and H2"), 1.25-1.35, 0.55-0.64, and 0.35-0.40 (m, 5H, cyclopropyl group);

1. additionwas added to the reaction
2. additioncontaining AG1-X2 (OH-- form, 2.5×10 cm)
3. washeluted with MeOH
4. additionFractions containing product
5. concentrationconcentrated
6. customflash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (9:1)
7. customSolvent was removed

ORD record

ord-edb0ca57293e46ebb51c1bc2d314b27e

Source dataset

uspto-grants-1997_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05663154