反应详情

1-(1-benzyl-4-piperidinyl)-3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate D) (4.3 g, 11.10 mmol), 4-phenoxyphenylboronic acid (Intermediate V) (2.61 g, 12.21 mmol), palladium tetrakistriphenyphosphine(0.77 g, 0.67 mmol) and sodium carbonate(2.82 g, 26.65 mmol) were mixed with ethylene glycol dimethyl ether(100 ml) and water(50 ml). The reaction mixture was heated to reflux overnight. Organic solvent was removed and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed, dried and evaporated. The residue was purified via flash column chromatography using ethyl acetate/methanol (98/2) as mobile phase to give 2.65 g of 1-(1-benzyl-4-piperidinyl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine. 1H NMR (CDCl3) 1.99(d, J=11.02 Hz, 2H), 2.25(m, 2H), 2.47 (m, 2H), 3.07(d, J=11.12 Hz), 3.59(s, 2H), 4.80(m, 1H), 5.52(s, 2H), 7.07(d, J=0.67, 1H), 7.15(m, 3H), 7.37(m, 6H), 7.66(d, J=8.51, 2H), 8.37(s, 1H); LC/MS (MH+=477).

1. temperatureThe reaction mixture was heated
2. temperatureto reflux overnight
3. customOrganic solvent was removed
4. extractionthe aqueous layer was extracted with ethyl acetate
5. washThe combined organic layer was washed
6. customdried
7. customevaporated
8. customThe residue was purified via flash column chromatography