Hydrogen Bromide → 4-Chloro-7-[3,5-bis-o-(2,4-dichlorobenzyl)-2-c-methyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine

Participants

Reaction Conditions

Reaction Steps

To a solution of the compound from Step C (9.42 g, 19 mmol) in anhydrous dichloromethane (285 mL) at 0° C. was added HBr (5.7 M in acetic acid, 20 mL, 114 mmol) dropwise. The resulting solution was stirred at 0° C. for 1 h and then at rt for 3 h, evaporated in vacuo and co-evaporated with anhydrous toluene (3×40 mL). The oily residue was dissolved in anhydrous acetonitrile (50 mL) and added to a solution of sodium salt of 4-chloro-1H-pyrrolo[2,3-d]pyrimidine [for preparation, see J. Chem. Soc., 131 (1960)] in acetonitrile [generated in situ from 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (8.76 g, 57 mmol) in anhydrous acetonitrile (1000 mL), and NaH (60% in mineral oil, 2.28 g, 57 mmol), after 4 h of vigorous stirring at room temperature]. The combined mixture was stirred at room temperature for 24 h, and then evaporated to dryness. The residue was suspended in water (250 mL) and extracted with EtOAc (2×500 mL). The combined extracts were washed with brine (300 mL), dried over Na2SO4, filtered and evaporated. The crude product was purified on a silica gel column (10 cm×10 cm) using ethyl acetate/hexane (1:3 and 1:2) as the eluent. Fractions containing the product were combined and evaporated in vacuo to give the desired product (5.05 g) as a colorless foam. 1H NMR (CDCl3): δ 0.93 (s, 3H, CH3), 3.09 (s, 1H, OH), 3.78 (dd, 1H, J5′,5″=10.9 Hz, J5′,4=2.5 Hz, H-5′), 3.99 (dd, 1H, J5″,4=2.2 Hz, H-5″), 4.23-4.34 (m, 2H, H-3′, H-4′), 4.63, 4.70 (2d, 2H, Jgem=12.7 Hz, CH2Ph), 4.71, 4.80 (2d, 2H, Jgem=12.1 Hz, CH2Ph), 6.54 (d, 1H, J5,6=3.8 Hz, H-5), 7.23-7.44 (m, 10H, 2Ph).

Provenance & Evidence