186519-89-1

876343-09-8

General procedure for the synthesis of 4-chloro-6-iodo-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidines from 4-chloro-7-(phenylsulfonyl)-7H-pyrrolo[2,3]pyrimidines: 4-chloro-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidines (10.0 g, 34.0 mmol) was dissolved in anhydrous THF, protected by nitrogen gas (300 ml) and cooled to -78°C. Lithium diisopropylammonium (2M solution of THF/n-heptane/ethylbenzene, 26 mL, 51.1 mmol) was added slowly dropwise over 30 min using a syringe pump. After 1 hour of reaction, iodine (11.2 g, 44.3 mmol) dissolved in anhydrous THF (60 mL) was added dropwise over 30 minutes using a syringe pump. The reaction mixture was continued to be stirred for 1 hr, followed by the addition of 1 M HCl solution (180 ml). The reaction mixture was stirred until the temperature of the reaction mixture increased to 22°C and then concentrated. Dichloromethane (250 ml) and water (200 ml) were added to the concentrate and the organic layer was separated. The aqueous phase was extracted with dichloromethane (2 x 90 ml) and the combined organic phases were washed with brine (100 ml), dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was recrystallized by acetonitrile (150 ml) to afford the light yellow solid product 4-chloro-6-iodo-7-(phenylsulfonyl)-7H-pyrrolo[2,3]pyrimidine (10.5 g, 25.1 mmol, 74% yield) with a melting point of 190 °C (decomposition). The purity of the product was 99% as determined by HPLC (retention time t R = 25.9 min).1H NMR (400 MHz, DMSO-d6) δ: 8.77 (s, 1H), 8.12-8.09 (m, 2H), 7.82-7.78 (m, 1H), 7.71-7.67 (m, 2H), 7.34 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 153.3, 152.1, 150.0, 137.2, 135.5, 130.0 (2C), 127.6 (2C), 120.6, 116.6, 84.6; IR (neat, cm-1): 1394, 1087, 724; HRMS (EI, m/z): 418.8988 (calculated value: C12H7ClIN3S, 418.8987, [M]+).