反应详情

温度

40 °C

2-Cyclopropyl-1-(4-fluoro-phenyl)-4-iodo-1H-imidazole (V-1) (150 mg, 0.46 mmol) and 2-methyl-4-trimethylsilanylethynyl-pyridine (113 mg, 0.59 mmol) were dissolved in 4 mL dry THF. This mixture was evacuated and backfilled with argon several times to remove oxygen from the solution. In a second reaction vessel triphenylphosphine (4 mg, 0.01 mmol), bis(triphenylphosphine)-palladium(II)chloride (16 mg, 0.02 mmol), copper(I)iodide (1 mg, 0.01 mmol) and triethyl amine (0.10 mL, 0.69 mmol) were dissolved in 2 mL dry THF. This mixture was also evacuated and backfilled with argon several times to remove oxygen from the solution. This mixture was heated to 40° C. and the solution of 2-cyclopropyl-1-(4-fluoro-phenyl)-4-iodo-1H-imidazole and 2-methyl-4-trimethylsilanylethynyl-pyridine was added dropwise. The reaction mixture was heated to 60° C. and tetrabutylammonium fluoride solution (1M in THF, 0.72 mL, 0.69 mmol) was added dropwise during 5 min. The reaction was than stirred at 40° C. for 2 hours. The mixture was taken up in 20 mL water and extracted three times with ethyl acetate (20 mL each). The combined organic extracts were dried with magnesium sulfate, filtered and evaporated. The crude product was purified by chromatography on silica gel (n-heptane/ethyl acetate 1:4) to obtain the desired title compound as a colorless solid (85 mg, 59%),

1. customThis mixture was evacuated
2. customto remove oxygen from the solution
3. customThis mixture was also evacuated
4. customto remove oxygen from the solution
5. additionthe solution of 2-cyclopropyl-1-(4-fluoro-phenyl)-4-iodo-1H-imidazole and 2-methyl-4-trimethylsilanylethynyl-pyridine was added dropwise
6. temperatureThe reaction mixture was heated to 60° C.
7. extractionextracted three times with ethyl acetate (20 mL each)
8. dry with materialThe combined organic extracts were dried with magnesium sulfate
9. filtrationfiltered
10. customevaporated
11. customThe crude product was purified by chromatography on silica gel (n-heptane/ethyl acetate 1:4)