Potassium Phosphate, Tribasic → 4-chloro-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

Participants

Reaction Steps

A mixture of 4-chloro-5-iodo-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (C1) (2.0 g, 4.9 mmol), 1-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (C17) (1.91 g, 6.87 mmol), potassium phosphate (4.0 g, 19 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.10 g, 87 μmol) was degassed several times with nitrogen and irradiated in a microwave synthesizer at 130° C. for 1.5 hours. The reaction mixture was partitioned between ethyl acetate (400 mL) and water (60 mL), and the aqueous layer was extracted with ethyl acetate (200 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (100 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. Chromatography on silica gel (Gradient: 10% to 80% ethyl acetate in petroleum ether) afforded the product as a brown oil. Yield: 1.33 g, 3.06 mmol, 62%. 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 7.87 (s, 1H), 7.76 (s, 1H), 7.38 (s, 1H), 5.68 (s, 2H), 5.46 (dd, J=9.4, 2.9 Hz, 1H), 4.08-4.15 (m, 1H), 3.71-3.79 (m, 1H), 3.57 (dd, J=8.3, 8.0 Hz, 2H), 2.04-2.24 (m, 3H), 1.61-1.79 (m, 3H), 0.94 (dd, J=8.3, 8.3 Hz, 2H), −0.03 (s, 9H).

Provenance & Evidence