反应详情

2-(6-Chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (0.5 g, 1.12 mmol) was dissolved in DMF (5.6 ml) and cooled in an ice bath. Sodium hydride (60% dispersion, 67 mg, 1.68 mmol) was carefully added. The mixture was stirred for 10 min then iodomethane (84 ul, 1.35 mmol) was added and the reaction was warmed to room temperature and stirred for 18 h. Water and ethyl acetate were added to the reaction. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed water and sodium chloride solution and dried over sodium sulfate. After evaporation the remaining residue was purified by silica gel chromatography (ethyl acetate/dichloromethane) to give 257 mg (50%) of 2-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde. (M+H)+=460.

1. temperaturecooled in an ice bath
2. stirringstirred for 18 h
3. customThe layers were separated
4. extractionthe aqueous layer was extracted twice more with ethyl acetate
5. washThe combined organic layers were washed water and sodium chloride solution
6. dry with materialdried over sodium sulfate
7. customAfter evaporation the remaining residue
8. customwas purified by silica gel chromatography (ethyl acetate/dichloromethane)