Water → 4-{4-[4-(azetidin-1-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-1-methyl-1H-pyrazol-5-yl}benzaldehyde

Participants

Reaction Conditions

Reaction Steps

4-(Azetidin-1-yl)-3-(5-bromo-1-methyl-1H-pyrazol-4-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidine (C28) (345 mg, 0.991 mmol), (4-formylphenyl)boronic acid (163 mg, 1.09 mmol), tetrakis(triphenylphosphine)palladium(0) (11.6 mg, 0.0100 mmol), and sodium carbonate (210 mg, 1.98 mmol) were combined in ethanol (10 mL). Water (2 mL) was added, and the reaction mixture was allowed to stir for 18 hours at 100° C. The reaction mixture was concentrated in vacuo and diluted with water. The aqueous layer was extracted with ethyl acetate (3×100 mL), and the combined organic layers were dried over sodium sulfate, filtered, concentrated under reduced pressure, and subjected to silica gel chromatography [Gradient: 0% to 100% (90:5:5 ethyl acetate/methanol/triethylamine) in heptane]. The product was obtained as a mixture with some impurities, and was used in the next step without additional purification. Yield: 270 mg, 0.723 mmol, 73%. APCI m/z 374.0 (M+1). 1H NMR (400 MHz, CD3OD), product peaks only: δ 2.25-2.34 (m, 2H), 3.8-4.0 (br m, 4H), 3.95 (s, 3H), 3.96 (s, 3H), 7.61 (br d, J=8.2 Hz, 2H), 7.76 (s, 1H), 7.92 (br d, J=8.4 Hz, 2H), 8.16 (s, 1H), 9.97 (s, 1H).

Provenance & Evidence