General procedure for the synthesis of 4-chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidines from 5-bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidines: 5-bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidines (0.6 g, 2.60 mmol) were dissolved in 30 mL of dry tetrahydrofuran (THF) and cooled to -78 °C. 4.10 mL of n-butyllithium (nBuLi, 1.6 M solution in hexane) was added dropwise over 10 min. The reaction mixture was stirred at -78 °C for 20 min, followed by dropwise addition of N-fluorobenzenesulfonimide (NFSI, 3.38 mmol, 1.065 g, dissolved in 6.5 mL of anhydrous THF) over 15 min. The reaction mixture was slowly warmed to room temperature and stirred overnight. Upon completion of the reaction, the reaction was quenched by the addition of 2 mL of water, and then the mixture was evaporated to dryness. The crude product was partitioned between ethyl acetate (EtOAc, 40 mL) and saturated ammonium chloride solution (20 mL), and the aqueous layer was extracted with 20 mL EtOAc. The organic layers were combined, washed with 20 mL of water and subsequently dried over anhydrous magnesium sulfate (MgSO?). After filtration, the solvent was evaporated. The crude product was purified by silica gel column chromatography using 4% methanol/dichloromethane (MeOH/CH?Cl?) as eluent to afford 4-chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine (0.36 g, 71% yield).1H NMR (DMSO-d?) δ: 7.70 (s, 1H), 8.62 (s, 1H), 12.25 (s, 1H (NH).
![5-Bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidine](/CAS/GIF/22276-95-5.gif)
![4-Chloro-5-fluoro-7H-pyrrolo[2,3-d]-pyrimidine](/CAS/GIF/582313-57-3.gif)