To a 1L three-necked round-bottomed flask was added 6-chloro-9H-purine (15.4 g, 0.1 mol, 1 eq.) and tetrahydrofuran (155 mL) at 0 °C and protected by nitrogen in an inert atmosphere. Methylmagnesium chloride (MeMgCl, 36.6 mL, 1.0 M THF solution, 1.1 eq.) was added dropwise with stirring. The reaction mixture was continued to be stirred at 0 °C for 30 min. Subsequently, iodomethane (42.6 g, 3 eq.) was added slowly and dropwise with stirring. The resulting reaction solution was transferred to a 50 °C oil bath and the reaction was stirred for 5 hours. Upon completion of the reaction, the reaction was quenched by addition of 50 mL of aqueous ammonium chloride (NH4Cl) and extracted with dichloromethane (3 x 50 mL). The organic layers were combined and washed with brine (2 x 50 mL) and subsequently concentrated under vacuum. The crude product was recrystallized by dichloromethane/petroleum ether (1:10) to afford 6-chloro-7-methylpurine as a light green solid (7 g, 42% yield).
