反应详情

温度

120 °C

A suspension of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (K5) (0.252 g, 0.552 mmol), methyl 2-(2-ethynyl-4-fluorophenyl)acetate (A50) (0.106 g, 0.552 mmol), PPh3 (0.007 g, 0.03 mmol), CuI (0.005 g, 0.03 mmol) and PdCl2(PPh3)2 (0.019 g, 0.028 mmol) in DMF (3 mL) and Et3N (1.0 mL) was heated under microwave irradiation for 20 minutes at 120° C. The resulting mixture was diluted with EtOAc (100 mL) then washed with water (100 mL), brine (25 mL) and dried over MgSO4. The volatiles were evaporated in vacuo and the residue was adsorbed onto silica gel and purified using column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-80% EtOAc in petroleum benzine 40-60° C.) to give the title compound A51 as a yellow solid (0.158 g, 47%); 1H NMR (400 MHz, CDCl3) δ 8.64 (d, J=1.0 Hz, 1H), 7.75 (s, 1H), 7.62-7.55 (m, 2H), 7.38-7.27 (m, 2H), 7.25-7.19 (m, 2H), 7.14 (td, J=8.3, 2.7 Hz, 1H), 4.36-4.20 (m, 2H), 3.92 (s, 2H), 3.72 (s, 3H), 2.82 (t, J=12.8 Hz, 2H), 2.66 (td, J=8.5, 4.2 Hz, 1H), 1.89-1.78 (m, 2H), 1.70-1.54 (m, 2H), 1.51 (s, 9H). LCMS-A: rt 1.852 min; m/z 613 [M+H]+.

1. washthen washed with water (100 mL), brine (25 mL)
2. dry with materialdried over MgSO4
3. customThe volatiles were evaporated in vacuo
4. custompurified
5. customcolumn chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-80% EtOAc in petroleum benzine 40-60° C.)