反应详情

A mixture of [A] 7-amino-4-bromo-2-methyl-2,3-dihydro-1H-isoindol-1-one (1.0 g, 4.1 mmol), and 1-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole [US 2007265272] (1.6 g, 5.0 mmol) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.17 g, 0.21 mmol) in a microwave tube was taken up in 1,4-Dioxane (12 mL). The mixture was treated with a solution of Potassium carbonate (1.7 g, 12 mmol) in H2O (3.0 mL, 170 mmol), flushed with N2, sealed and irradiated in the CEM for 30 minutes at 100° C. Another 1 g of boronic ester was added as well as another 0.05 eq of catalyst. The mixture was sparged with N2, sealed and irradiated for 45 min. This was worked up and purified. 1H NMR (400 MHz, DMSO-d6) δ 1.36-1.50 (m, 4H), 1.57 (td, J=9.22, 3.03 Hz, 1H), 1.63-1.71 (m, 1H), 3.03 (s, 3H), 3.35-3.41 (m, 1H), 3.57 (ddd, J=11.31, 8.40, 3.03 Hz, 1H), 3.75 (dt, J=10.80, 5.34 Hz, 1H), 3.91-3.99 (m, 1H), 4.27-4.33 (m, 2H), 4.44 (s, 2H), 4.55 (t, J=3.28 Hz, 1H), 6.06 (s, 2H), 6.62 (d, J=8.34 Hz, 1H), 7.43 (d, J=8.34 Hz, 1H), 7.74 (d, J=0.51 Hz, 1H), 7.95 (d, J=0.51 Hz, 1H).

1. customflushed with N2
2. customsealed
3. customirradiated in the CEM for 30 minutes at 100° C
4. customThe mixture was sparged with N2
5. customsealed
6. customirradiated for 45 min
7. custompurified