反应详情

温度

0 °C

2-Chloro-N-cyclopropyl-4-iodobenzamide (1.0 g, 3.11 mmol) and propiolic acid (222 mg, 3.11 mmol) were dissolved in N,N-dimethylformamide (1.2 ml) and cooled to 0° C. Then bis(triphenylphosphine)palladium(II) dichloride (43 mg, 0.06 mmol) and copper(I) iodide (23 mg, 0.12 mmol) were added and the mixture was cooled to −10° C. After addition of diisopropylamine (786 mg, 7.77 mmol), the mixture was warmed slowly to room temperature and stirred overnight. The reaction mixture was diluted with ethyl acetate, washed successively with hydrochloric acid (2 M) and saturated sodium chloride solution, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure. The residue was dissolved in N,N-dimethylformamide (1 ml) and admixed with 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (973 mg, 3.52 mmol) and 2,2,2-trifluoro-1-[3-trifluoromethylphenyl]ethanamine (780 mg, 3.20 mmol) and stirred at room temperature overnight. The reaction solution was admixed with hydrochloric acid (1 M) and extracted with ethyl acetate. The organic phase was washed with saturated sodium hydrogencarbonate solution and saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure. The residue was purified by means of silica gel chromatography with the eluent cyclohexane/ethyl acetate (EA) (0% EA to 40% EA).

1. temperaturethe mixture was cooled to −10° C
2. temperaturethe mixture was warmed slowly to room temperature
3. washwashed successively with hydrochloric acid (2 M) and saturated sodium chloride solution
4. dry with materialdried over magnesium sulphate
5. filtrationfiltered
6. concentrationconcentrated to dryness under reduced pressure
7. dissolutionThe residue was dissolved in N,N-dimethylformamide (1 ml)
8. stirringstirred at room temperature overnight
9. extractionextracted with ethyl acetate
10. washThe organic phase was washed with saturated sodium hydrogencarbonate solution and saturated sodium chloride solution
11. dry with materialdried over sodium sulphate
12. filtrationfiltered
13. concentrationconcentrated to dryness under reduced pressure
14. customThe residue was purified by means of silica gel chromatography with the eluent cyclohexane/ethyl acetate (EA) (0% EA to 40% EA)