1012785-51-1

General procedure for the synthesis of 2,4-dichloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidines using 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidines as starting material: 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidines (950 g, 5.053 mol) and dichloromethane (16 L) were added to a 50 L jacketed reactor. The resulting tan suspension was cooled to 16 °C and N-iodosuccinimide (1598 g, 7.104 mol) was added in batches over 20 min. The reaction mixture was stirred at room temperature for 16 h. Subsequently, the reaction was confirmed to be complete by thin-layer chromatography (TLC) analysis (unfolding agent ratio 2:1 hexane/ethyl acetate). The resulting precipitate was filtered, washed with dichloromethane (3 x 1.5 L) and dried under reduced pressure at 40 °C for 64 h to afford 1447 g (yield: 91%) of 2,4-dichloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine as a beige solid. Mass spectrum (ESI) m/z 314.0 [M + 1]+.

[1] Patent: US2014/200206, 2014, A1. Location in patent: Paragraph 0221
[2] Helvetica Chimica Acta, 2008, vol. 91, # 6, p. 1083 - 1105
[3] Patent: WO2018/85833, 2018, A2. Location in patent: Paragraph 0443
[4] Patent: US2009/54425, 2009, A1. Location in patent: Page/Page column 30-31
[5] Patent: WO2009/131687, 2009, A2. Location in patent: Page/Page column 98