反应详情

温度

100 °C

To a sealed tube were added (S)-2-((3-chloro-1,4-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)oxy)-N-(1-(p-tolyl)ethyl)acetamide (50 mg, 0.13 mmol), Pd[P(tBu)3)]2 (3.4 mg, 6.7 μmol), CsF (45 mg, 0.30 mmol), [(t-Bu)3PH]BF4 (3.9 mg, 0.013 mmol) and Pd2(dba)3 (6.1 mg, 6.7 μmol). The tube was evacuated and flushed 3 times with argon and then 3-fluoro-2-tributylstannyl-pyridine (104 mg, 0.27 mmol) in dioxane (1 ml) was added and the suspension heated at 100° C. for 16 h. After cooling to rt, CH2Cl2 and NaHCO3 solution were added and the phases separated. The organic layers were washed with water, dried over Na2SO4 and the solvents removed under reduced pressure. Purification using preparative reverse phase chromatography (LC SunFire C18 OBD column) followed by liberation of the free base (SPE cartridge SCX-1, eluent 7M NH3 in methanol) yielded the title compound (3.7 mg, 6%). [1H-NMR (DMSO-d6, 600 MHz) δ 8.59 (d, 1H), 8.54 (d, 1H), 7.91 (t, 1H), 7.62-7.58 (m, 1H), 7.18 (d, 2H), 7.08 (d, 2H), 6.64 (s, 1H), 4.96 (q, 1H), 4.87 (d, 1H), 4.84 (d, 1H), 3.89 (s, 3H), 2.30 (s, 3H), 2.25 (s, 3H), 1.37 (d, 3H); HPLC-MS RtJ=1.08 min; [M+H]+=434.1]

1. customThe tube was evacuated
2. customflushed 3 times with argon
3. temperatureAfter cooling to rt
4. customthe phases separated
5. washThe organic layers were washed with water
6. dry with materialdried over Na2SO4
7. customthe solvents removed under reduced pressure
8. customPurification