反应详情

温度

-78 °C

A solution of (4-methoxy-phenyl)-(2-methyl-quinazolin-4-yl)-amine (100 mg, 0.35 mmol) in 3 mL of dimethylformamide in a 15 mL high pressure reaction vessel was cooled to −78° C. Diflurochloromethane (about 0.8 mL) was condensed into the solution, then cesium carbonate (160 mg, 0.49 mmol) was added. The reaction vessel was capped and heated at 80° C. overnight. The reaction mixture was cooled to room temperature and cooled to −78° C. and the seal tube was uncapped, warm to room temperature and allowed to stand for 2 h. The reaction mixture was diluted with 50 mL of ethyl acetate and the organic layer was washed with water (50 mL×3), followed by saturated aqueous NaCl. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by chromatography (30% ethyl acetate/hexane, 6 drops triethylamine/500 mL of solvent) to give the title compound (35 mg, 0.111 mmol, 32%). 1H NMR (CDCl3): 8.35 (dd, J=1.8, 8.1, 1H), 7.35-(m, 3H), 7.25 (t, J=72.1, 1H), 7.21-7.25 (m, 2H), 6.86-6.91 (m, 2H), 3.82 (s, 3H), 2.48 (s, 3H).

1. customcondensed into the solution
2. customThe reaction vessel was capped
3. temperatureheated at 80° C. overnight
4. temperatureThe reaction mixture was cooled to room temperature
5. temperaturecooled to −78° C.
6. temperaturewarm to room temperature
7. washthe organic layer was washed with water (50 mL×3)
8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified by chromatography (30% ethyl acetate/hexane, 6 drops triethylamine/500 mL of solvent)