反应详情

温度

140 °C

Example 107. A mixture of 2-(4-cyclopropyl-1H-imidazol-1-yl)-9-iodo-1-methyl-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (8 mg, 17 μmol), 3-methyl-5-(tributylstannyl)isoxazole (10 mg, 26 μmol) and Pd(PPh3)4 (1.0 mg, 0.9 μmol) in dioxane (0.2 mL) is heated to 140° C. for 1.5 h under N2 in a microwave reactor. The mixture was then concentrated in vacuo the residue obtained was purified by SFC (column: 2-Ethylpyridine 5 μm, 250×30 mm, 60A, Princeton; eluent: 8% MeOH/CO2 for 1 min, then from 8% MeOH/CO2 to 13% MeOH/CO2 in 6 min; then from 13% MeOH/CO2 to 50% MeOH/CO2 in 1 min; flow 100 mL/min; UV detection at 220 nm) to afford the title compound (4 mg) as a beige solid. UPLC-MS: MS 414.2 (M+H+); UPLC rt 0.88 min. 1H NMR (400 MHz, CHLOROFORM-d): δ ppm 0.74-0.88 (m, 4 H); 1.74-1.91 (m, 1 H); 2.18 (s, 3 H); 2.42 (s, 3 H); 2.81 (td, J=14.68, 5.27 Hz, 1 H); 3.17 (td, J=13.49, 3.64 Hz, 1 H); 3.45 (m., 1 H); 3.91-4.02 (m, 2 H); 4.70 (d, J=10.79 Hz, 1 H); 6.32 (s, 1 H); 6.95 (s, 1 H); 7.45 (t, J=7.65 Hz, 1 H); 7.56 (d, J=7.78 Hz, 1 H); 7.66-7.76 (m, 2 H).

1. concentrationThe mixture was then concentrated in vacuo the residue
2. customobtained
3. customwas purified by SFC (column
4. waitfrom 8% MeOH/CO2 to 13% MeOH/CO2 in 6 min
5. waitthen from 13% MeOH/CO2 to 50% MeOH/CO2 in 1 min