反应详情

温度

90 °C

The product of Step 1 (70 mg, 0.24 mmol), Intermediate 4 (5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-one, 77 mg, 0.3 mmol), tetrakis palladium triphenylphosphine (69 mg, 0.06 mmol), sodium carbonate solution (1.5 M, 1.28 mL, 1.92 mmol) and dioxane (3.8 mL) are combined in a flask. The mixture is degassed with nitrogen for 10 min then sealed and heated at 90° C. for 16 h. Brine is added and the mixture is washed with dichloromethane followed by ethyl acetate. The combined organic layers are dried over MgSO4 and evaporated in vacuo to afford a brown oil. The crude material is purified by column chromatography, eluting with 5% methanolic ammonia (7 N) in dichloromethane to give a brown solid. Trituration with 1:1 toluene:diethyl ether yielded the title compound as an off-white solid (30 mg, 37%). 1H-NMR (400 MHz, d6-DMSO) =1.22-1.29 (m, 1H), 1.32-1.49 (m, 4H), 1.64 (d, 1H, J=15.2 Hz), 1.77 (d, 2H, J=12.8 Hz), 1.92 (d, 2H, J=15.2 Hz), 3.97-4.01 (1H, m), 7.33 (d, 1H, J=8.4 Hz), 7.48 (s, 1H), 7.63 (s, 1H), 7.92 (s, 1H). LCMS: Rt 2.24 min (99.6%), m/z (APCI) 348 (M+H)+.

1. customThe mixture is degassed with nitrogen for 10 min
2. customthen sealed
3. additionBrine is added
4. washthe mixture is washed with dichloromethane
5. dry with materialThe combined organic layers are dried over MgSO4
6. customevaporated in vacuo
7. customto afford a brown oil
8. customThe crude material is purified by column chromatography
9. washeluting with 5% methanolic ammonia (7 N) in dichloromethane
10. customto give a brown solid