反应详情

温度

65 °C

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)+.

1. washthe resulting mixture was washed with water (20 mL)
2. extractionThe aqueous layer was extracted with EtOAc (three×10 mL)
3. washthe combined organic layers were then washed with 1 M aqueous Na2SO3 (20 mL), sat. aqueous NaHCO3 (20 mL), brine (20 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was then purified via flash chromatography (20%-50% EtOAc/heptane)