Sodium hydride → 2,4-Dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

Participants

Reaction Conditions

Reaction Steps

A solution of 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (0.30 g, 1.6 mmol) in anhydrous N,N-dimethylformamide (5.5 mL) cooled to 0° C. was treated with a 60% dispersion of sodium hydride in mineral oil (82.5 mg, 2.06 mmol) under nitrogen. The reaction was stirred at 0° C. for 20-25 min. At this time, the reaction was treated with (2-(chloromethoxy)ethyl)trimethylsilane (340 μL, 1.92 mmol) and was purged with nitrogen. The ice/water bath was removed, and the reaction was stirred at room temperature over 3 nights. At this time, the reaction was diluted with water (50 mL) and was extracted with ethyl acetate (2×50 mL). The combined organics were washed with water (50 mL) and a saturated aqueous sodium chloride solution (50 mL), dried over magnesium sulfate, filtered and rinsed with ethyl acetate, and concentrated in vacuo onto Celite®. Flash chromatography (12 g silica gel column, 1-30% ethyl acetate/hexanes) afforded 2,4-dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine as a viscous yellow oil (336.5 mg, 66.3%). 1H NMR (300 MHz, DMSO-d6) δ ppm −0.18-−0.01 (m, 9H) 0.74-0.94 (m, 2H) 3.43-3.62 (m, 2H) 5.60 (s, 2H) 6.78 (d, J=3.77 Hz, 1H) 7.90 (d, J=3.77 Hz, 1H). LC-MS calcd. for C12H18Cl2N3OSi [(M+H)+] 318, obsd. 317.9.

Provenance & Evidence