Ethyl Acetate → 2,4-dichloro-5-(pyridin-2-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

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Reaction Conditions

Reaction Steps

To a solution of 2,4-dichloro-5-iodo-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (1.0 g, 2.25 mmol), as prepared in Example 5, step 1, in THF (11 mL) was added tetrakis(triphenylphosphine)palladium(0) (131 mg, 0.113 mmol) and pyridin-2-ylzinc(II) bromide (9 mL, 4.5 mmol, 0.5 M solution in THF) which was then heated to 65° C. and stirred for 3 hrs. EtOAc (10 mL) was added and the resulting mixture was washed with water (20 mL). The aqueous layer was extracted with EtOAc (three×10 mL), and the combined organic layers were then washed with 1 M aqueous Na2SO3 (20 mL), sat. aqueous NaHCO3 (20 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was then purified via flash chromatography (20%-50% EtOAc/heptane) to give the title compound as a clear oil (378 mg, 43% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.59-8.71 (m, 1H) 8.21 (s, 1H) 7.89 (td, J=7.77, 1.89 Hz, 1H) 7.70 (d, J=7.83 Hz, 1H) 7.39 (ddd, J=7.52, 4.86, 1.01 Hz, 1H) 5.67 (s, 2H) 3.50-3.67 (m, 2H) 0.79-0.95 (m, 2H) −0.17-0.00 (m, 9H). m/z (APCI+) for C17H20N4OCl2Si 395.00/397.00 (M+H)+.

Provenance & Evidence