反应详情

温度

150 °C

To a mixture of (1-methyl-1H-indol-2-yl)boronic acid (37.7 mg mg, 0.215 mmol), 2-(4-iodophenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide (50.0 mg, 0.108 mmol), tricyclohexylphosphine (0.7 mg, 0.003 mmol), 1-hydroxy-7-azabenzotriazole (101 mg, 0.744 mmol) and Pd2(dba)3 (1 mg, 0.001 mmol) were added dioxane (0.4 mL) and a solution of K3PO4 in H2O (0.2 mL, 1.27 M). The resulting solution was heated in microwave at 150° C. for 0.5 hr. The reaction was completed and diluted with EtOAc. The water later was removed. The remaining organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified by reverse-phase HPLC to give the product as a TFA salt (40 mg, 79%). 1H NMR (CDCl3, 400 MHz) δ 8.22 (dd, J=0.8, 2.8 Hz, 1H), 7.63 (d, J=8.0 Hz, 1H), 7.49 (dd, J=2.0, 6.4 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H), 7.37 (d, J=6.4, 1H), 7.27-7.19 (m, 2H), 7.14 (t, J=8.0 Hz, 1H), 6.80 (d, J=7.2 Hz, 1H), 6.56 (s, 1H), 5.14 (quintet, J=7.2 Hz, 1H), 4.38 (q, J=8.0 Hz, 2H), 3.75 (s, 3H), 3.65 (s, 2H), 1.44 (d, J=6.8 Hz, 3H); HRMS (ES) [M+1]+ calcd for C26H25F3N3O2: 468.1893, Found: 468.1889. FLIPR alpha1I IP=36 nM.

1. customThe water later was removed
2. dry with materialThe remaining organic phase was dried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated
5. customThe residue was purified by reverse-phase HPLC