A mixture of 4-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-cyclohexanone (20.0 g, 53.3 mmol), 1-methylpiperazine (6.42 g, 128 mmol) and acetic acid (7.7 g, 128 mmol) in 1,2-dichloromethane (1 L) was stirred for 15 minutes at ambient temperature. Sodium triacetoxyborohydride (14.7 g, 69.3 mmol) was added and stirring was continued for 20 hours. Water (400 mL) was added followed by sodium bicarbonate (26.0 g, 310 mmol). The mixture was transferred to a separatory funnel and the layers separated. The aqueous layer was extracted with dichloromethane (300 mL). The combined organic extracts were dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure. The resulting oil was purified by flash chromatography on silica gel (275 g) using dichloromethane/methanol (9:1) as an eluent to give cis-4-chloro-5-iodo-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine (10.2 g, 42%) and trans-4-chloro-5-iodo-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine (5.8 g) which contained 10% of the cis isomer. This mixture was stirred in diethyl ether (100 mL) for 1.5 hours then the solid was collected by filtration to provide pure trans-4-chloro-5-iodo-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine (5.0 g, 20.2%).
