Reaction SMILES: C(O[CH:5]1[O:17][C@H:16]([CH2:18][O:19][C:20]([C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)=[O:21])[C@@H:15]([F:29])[C@H:6]1[O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=O)C.Br.CC(O)=O.[NH2:35][C:36]1[N:37]=[C:38]([Cl:45])[C:39]2[CH:44]=[CH:43][NH:42][C:40]=2[N:41]=1.[H-].[Na+]>C(Cl)Cl.CC#N>[NH2:35][C:36]1[N:37]=[C:38]([Cl:45])[C:39]2[CH:44]=[CH:43][N:42]([C@@H:5]3[O:17][C@H:16]([CH2:18][O:19][C:20]([C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=4)=[O:21])[C@@H:15]([F:29])[C@H:6]3[O:7][CH2:8][C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:40]=2[N:41]=1
Reactant: Nc1nc(Cl)c2cc[nH]c2n1
Reactant: CC(=O)OC1O[C@H](COC(=O)c2ccc(C)cc2)[C@@H](F)[C@H]1OCc1ccccc1
Agent: Br
Agent: [H-]
Agent: [Na+]
Solvent: CC#N
Solvent: CC(=O)O
Solvent: ClCCl
Product: Cc1ccc(C(=O)OC[C@H]2O[C@@H](n3ccc4c(Cl)nc(N)nc43)[C@H](OCc3ccccc3)[C@@H]2F)cc1
Temperature: -10 °C
Reaction time: 1 h
Yield: 36.8 %

Procedure:
A solution 1-O-acetyl-2-O-benzyl-5-O-(p-toluoyl)-3-deoxy-3-fluoro-D-ribofuranose (410 mg, 1.01 mmol) (prepared by a modified method described for similar sugar derivatives, Helv. Chim. Acta 82: 2052 (1999) and J. Med. Chem. 1991, 34, 2195) in anhydrous CH2Cl2 (1.5 mL) was cooled to −15° C. in a dry ice/CH3CN bath. After cooling the reaction mixture for 10 min. under the argon atmosphere, 33% HBr/AcOH (370 μL, 1.5 equiv.) was added slowly over 20 min keeping the bath temperature around −15° C. After the addition was complete, the reaction mixture was stirred at −10° C. for 1 hr. The solvent was removed under reduced pressure and the residue azeotroped with anhydrous toluene (5×10 mL). In a separate flask, 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (210 mg, 1.2 mmol) was suspended in anhydrous CH3CN (10 mL) and cooled to −10° C. To this was added 60% NaH dispersion in oil (57 mg) in two portions, and the reaction mixture was stirred for 45 min. during which time the solid dissolved and the bath temperature rose to 0° C. The bath was removed and stirring was continued for about 20 additional min. It was cooled back to −10° C. and the bromo sugar, prepared above, was taken up in anhydrous CH3CN (1.5 mL) and added slowly to the anion of nucleobase. After the addition was complete, the reaction mixture was stirred for an additional 45 min allowing the temperature of the reaction to rise to 0° C. The bath was removed and the reaction allowed to stir at room temperature for 3 hr. Methanol was added carefully to the reaction mixture and the separated solid removed by filtration. The solvent was removed under reduced pressure and the residual oil dissolved in EtOAc (50 mL) and washed with water (3×20 mL). The organic layer was dried over Na2SO4 and concentrated to give an oil. It was purified by column chromatography to furnish fully protected 2-amino-7-(5-O-(p-toluoyl)-2-O-benzyl-3-deoxy-3-fluoro-β-D-ribofuranosyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (190 mg) as an α/β mixture (1:1). After conversion of 4-chloro to 4-oxo by heating the compound with 2N NaOH/dioxane mixture at 105° C. and after the usual workup the residue was debenzylated using 20 mol % w/w of 10% Pd/C and ammonium formate in refluxing methanol to give title compound after purification by HPLC; yield 10%. ESMS: calcd. for C11H13FN4O4 284.24, found 283.0 (M+1).