Pyridine → HCID 87236973, compound

Participants

Reaction Conditions

Reaction Steps

To a heterogeneous mixture of crystallized 2-chloro-9-(3′,5′-di-O-benzoyl-β-D-ribofuranosyl)-adenine (F) (65 g, purity: 94.7% by A % HPLC, 120.7 mmol) in DCM (650 mL) and pyridine (65 mL) at about 0 to 20° C. under an atmosphere of N2(g) was added Tf2O (85.1 g, 301.6 mmol) dropwise whilst maintaining the temperature within the range of 0 to 20° C. The mixture turned clear and the reaction was deemed complete when the HPLC purity of F was not more than 1%. The mixture was washed with saturated NaHCO3 (325 mL) and the organic phase was washed with 2 N H2SO4 (325 mL) at room temperature The organic phase was dried using 3 Å molecule sieves until the Karl Fischer titration value was <=1000 ppm. The organic phase was evaporated in vacuo at 40° C. until about 290 g of residue (including about 130 mL of DCM) remained. The residue was directly used in the next step. The typical purity of 2-chloro-9-(3′,5′-di-O-benzoyl-2′-O-trifluoromethylsulfonyl-β-D-ribofuranosyl)-adenine (G) was >=95% and the yield was >=95%. 1H NMR (300 MHz, CDCl3) δ 8.11 (dd, J=8.3, 1.2 Hz, 2H), 7.98 (dd, J=8.3, 1.2 Hz, 2H), 7.87 (s, 1H), 7.70-7.60 (m, 1H), 7.59-7.46 (m, 3H), 7.41 (t, J=7.7 Hz, 2H), 6.34-6.23 (m, 2H), 6.16 (dd, J=5.3, 3.2 Hz, 1H), 6.07 (bs, 2H), 4.86 (dd, J=12.2, 3.3 Hz, 1H), 4.81-4.74 (m, 1H), 4.65 (dd, J=12.2, 4.2 Hz, 1H).

Provenance & Evidence