反应详情

温度

80 °C

A mixture of 4-chloro-7-(1,4-dioxaspiro[4.5]dec-8-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (3.0 g, 7.15 mmol) in ethylene glycol dimethyl ether (100 mL) was treated with 4-(benzyloxy)phenylboronic acid (1.79 g, 7.87 mmol), tetrakis(triphenylphosphine)palladium (0.496 g, 0.429 mmol), and a solution of sodium carbonate (1.83 g, 17.16 mmol) in water (50 mL). A precipitate formed after 20 minutes. Reaction was stirred for 5 hours at 80° C. under a nitrogen atmosphere. The mixture was allowed to cool to room temperature and the organic solvent was removed under reduced pressure. The product was partitioned between the aqueous sodium carbonate layer and ethyl acetate. The aqueous layer was further extracted with ethyl acetate three times. The organic layers were combined, washed with water and brine, dried over magnesium sulfate, and partially concentrated until a precipitate formed. The solid was filtered, washed with ethyl acetate, and dried under a high vacuum. Yielded 2.06 g (61%) of 5-[4-(benzyloxy)phenyl]-4-chloro-7-(1,4-dioxaspiro[4.5]dec-8-yl)-7H-pyrrolo[2,3-d]pyrimidine. 1H NMR (DMSO-d6, 400 MHz) δ 8.64(s, 1H), 7.88(s, 1H), 7.52-7.33(m, 7H), 7.08-7.05(d, 2H, J=12 Hz), 5.15(s, 2H), 4.82-4.78 (m, 1H), 3.95-3.89(m, 4H), 2.21-2.13(m, 2H), 1.98-1.96(m, 2H), 1.85-1.75(m, 4H); Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 8.356 min.

1. customA precipitate formed after 20 minutes
2. customReaction
3. temperatureto cool to room temperature
4. customthe organic solvent was removed under reduced pressure
5. customThe product was partitioned between the aqueous sodium carbonate layer and ethyl acetate
6. extractionThe aqueous layer was further extracted with ethyl acetate three times
7. washwashed with water and brine
8. dry with materialdried over magnesium sulfate
9. concentrationpartially concentrated until a precipitate
10. customformed
11. filtrationThe solid was filtered
12. washwashed with ethyl acetate
13. customdried under a high vacuum