2,4-dichloro-7-Methyl-7H-pyrrolo[2,3-d]pyriMidine

Synthesis

To a suspension of sodium hydride (480 mg, 12.00 mmol, 1.10 eq., 60% dispersed in mineral oil) in tetrahydrofuran (50 mL) was slowly added dropwise a solution of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (2 g, 10.64 mmol, 1.00 eq.) in tetrahydrofuran (50 mL). The reaction mixture was stirred at 0 °C for 30 min and then iodomethane (1.66 g, 11.70 mmol, 1.10 eq.) was added dropwise at the same temperature. After addition, the reaction system was brought to room temperature and stirred overnight. Upon completion of the reaction, the reaction was quenched by the addition of water (20 mL) to the mixture and subsequently extracted with ethyl acetate. The combined organic phases were washed with saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1:5, v/v) as eluent to afford 2.1 g (98% yield) of the title compound, 2,4-dichloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine, as a white solid.LC-MS (ESI, m/z): 202 [M+H]+.

References

[1] Patent: US2015/57260, 2015, A1. Location in patent: Paragraph 0436; 0437; 0588; 0589
[2] Patent: WO2015/25026, 2015, A1. Location in patent: Page/Page column 118
[3] Patent: WO2017/59191, 2017, A1. Location in patent: Paragraph 00235-00239
[4] Patent: WO2017/46739, 2017, A1. Location in patent: Page/Page column 51
[5] Patent: CN107226808, 2017, A. Location in patent: Paragraph 0366-0369