39929-79-8

90213-66-4

General procedure for the synthesis of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidines from 2,4-dihydroxypyrrolo[2,3-d]pyrimidines: 7H-pyrrolo[2,3-d]pyrimidine-2,4-diol (10.0 g, 66.2 mmol) and toluene (30 ml) were added to a reactor equipped with a stirrer. Phosphoryl chloride (18.5 ml, 198.5 mmol) was added slowly under stirring and the reaction system was subsequently warmed to 70 °C. Diisopropylethylamine (23.0 ml, 132.3 mmol) was added dropwise over 2.5 h to control the exothermic nature of the reaction. After the dropwise addition, the reaction temperature was raised to 106 °C and stirring was continued at this temperature for 16 hours. After completion of the reaction, the mixture was cooled to 25 °C and then slowly poured into a flask containing water (230 ml) and ethyl acetate (120 ml) and stirred overnight at room temperature. The reaction mixture was filtered through diatomaceous earth and then layered, the aqueous layer was extracted with ethyl acetate (3 x 75 ml). The organic layers were combined and washed with brine (100 ml). Darco KBB (1.24 g) was added to the organic layer, filtered again through diatomaceous earth and dried with anhydrous sodium sulfate (10.0 g). Finally, the solution was concentrated under reduced pressure to afford the target product 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine in 52% yield.