反应详情

温度

120 °C

A suspension of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide (A14) (150 mg, 446 μmol), Cs2CO3 (436 mg, 1.34 mmol) and 5-amino-2-trifluoromethylpyridine (145 mg, 892 μmol) in 1,4-dioxane (3 mL) was sonicated for 10 minutes. Xantphos (10.3 mg, 17.8 μmol) and Pd(OAc)2 (2.00 mg, 8.92 μmol) were added and the resulting mixture was heated under microwave irradiation for 20 minutes at 120° C. The resulting mixture was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. then 0-40% MeOH in EtOAc). The purified solid was dissolved in acetone (0.2 mL) and petroleum benzene 40-60° C. (30 mL) added. The precipitate was collected by vacuum filtration and the filter cake dried under high vacuum to yield the title compound 9 as a tan solid (62 mg, 30%); 1H NMR (400 MHz, CDCl3) δ 8.87 (d, J=2.6 Hz, 1H), 8.43-8.34 (m, 2H), 7.69 (d, J=8.7 Hz, 1H), 7.60 (s, 1H), 7.45 (d, J=8.2 Hz, 1H), 7.36 (dd, J=7.8, 3.1 Hz, 2H), 7.30 (d, J=4.9 Hz, 1H), 5.39 (d, J=8.9 Hz, 2H), 3.35-3.17 (m, 4H), 1.78 (s, 2H), 1.16 (s, 2H). LCMS-A: rt 4.816 min; m/z 462 [M+H]+.

1. customwas sonicated for 10 minutes
2. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.
3. dissolutionThe purified solid was dissolved in acetone (0.2 mL)
4. additionpetroleum benzene 40-60° C. (30 mL) added
5. filtrationThe precipitate was collected by vacuum filtration
6. customthe filter cake dried under high vacuum