Sodium Carbonate → N-(3-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

Participants

Reaction Conditions

Reaction Steps

4,6-dichloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (100 mg, 0.366 mmol), (3-acrylamidophenyl)boronic acid (70 mg, 0.366 mmol) and triphenylphosphine (4 mg, 0.015 mmol) were dissolved in a mixture of toluene (7 mL) and 1 M sodium carbonate (39 mg, 0.367 mmol). Palladium(II) acetate (2.0 mg, 0.009 mmol) was then added and the reaction mixture was stirred for 12 h at 80° C. The reaction mixture was then allowed to cool to room temperature and the solvent was removed in vacuo. The residue was dissolved in EtOAc (20 mL) and washed with water (10 mL). The organic layer was separated, the aqueous layer was extracted with EtOAc (20 ml), and organic layers were combined. The combined organic layers were washed with brine (20 mL), dried over Na2SO4 and then concentrated. The crude material was purified by flash chromatography (EtOAc/hexane 20%) to yield the title compound (70%). 1H NMR (400 MHz, CDCl3): δ 8.45 (m, 2H), 7.88 (d, 1H, J=8.0 Hz), 7.85 (d, 1H, J=8.0 Hz), 7.68 (s, 1H), 7.49 (t, 1H, J=8.0 Hz), 6.46 (m, 1H), 6.27 (m, 1H), 6.06 (d, 1H, J=10.4 Hz), 5.79 (d, 1H, J=10.0 Hz), 4.12 (m, 1H), 3.82 (t, 1H, J=10.0 Hz), 2.58 (m, 1H), 2.14 (m, 1H), 1.95 (m, 1H), 1.78 (m, 2H), 1.62 (m, 1H). ESI-MS: 384.10 [M+H]+.

Provenance & Evidence