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

温度

80 °C

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]+.

1. temperatureto cool to room temperature
2. customthe solvent was removed in vacuo
3. dissolutionThe residue was dissolved in EtOAc (20 mL)
4. washwashed with water (10 mL)
5. customThe organic layer was separated
6. extractionthe aqueous layer was extracted with EtOAc (20 ml), and organic layers
7. washThe combined organic layers were washed with brine (20 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated
10. customThe crude material was purified by flash chromatography (EtOAc/hexane 20%)

ORDレコード

ord-0fe36bb15e334844867635cc1c4010d9

出典データセット

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09296703B2