反应详情

Carbon tetrachloride (40 ml) was added to 5-[3-chloro-2-[5-methyl-2H-indazol-2-yl)phenyl]-2-(triphenylmethyl)-2H-tetrazole (4.0 g, 7.23 mmol) as obtained in Reference Example 16, and the mixture was stirred. Thereto were added N-bromosuccinimide (1.42 g, 7.96 mmol), and the mixture was refluxed under heating for an hour. Thereto were added N-bromosuccinimide (1.22 g, 6.89 mmol) and azobisisobutyronitrile (57 mg, 0.345 mmol), and the mixture was refluxed under heating for 2.5 hours. After cooling, the mixture was diluted with dichloromethane (40 ml), and poured into water (40 ml). The organic layer was dried over magnesium sulfate, filtered, and concentrated. The residue was dried in vacuo. The residue thus obtained was added to a solution obtained by adding, in a different reaction vessel, sodium hydride (0.257 g, 5.88 mmol) to 2-ethyl-5,7-dimethyl-1H-imidazo[4,5-b]pyridine (1.03 g, 5.88 mmol) in DMF (39 ml) and stirring the solution for 30 minutes. The mixture was stirred at room temperature for 15 hours, concentrated, and partitioned by ethyl acetate (100 ml) and water (100 ml). The water layer was extracted with ethyl acetate (100 ml) and then with dichloromethane (100 ml). The organic layer was dried over magnesium sulfate, and then filtered. The filtrate was concentrated and subjected to flash chromatography on silica gel using a mixed solvent of hexane/ethyl acetate (2:3), whereby 0.992 g of 3-{[3-bromo-2-[3-chloro-2-(2-(triphenylmethyl)-2H-tetrazol-5-yl)phenyl]-2H-indazol-5-yl]methyl}-2-ethyl-5, 7-dimethyl-3H-imidazo[4,5-b]pyridine was obtained.

1. customas obtained in Reference Example 16
2. temperaturethe mixture was refluxed
3. temperatureunder heating for an hour
4. temperaturethe mixture was refluxed
5. temperatureunder heating for 2.5 hours
6. temperatureAfter cooling
7. dry with materialThe organic layer was dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was dried in vacuo
11. customThe residue thus obtained
12. additionwas added to a solution
13. customobtained
14. additionby adding, in a different reaction vessel
15. stirringThe mixture was stirred at room temperature for 15 hours
16. concentrationconcentrated
17. custompartitioned by ethyl acetate (100 ml) and water (100 ml)
18. extractionThe water layer was extracted with ethyl acetate (100 ml)
19. dry with materialThe organic layer was dried over magnesium sulfate
20. filtrationfiltered
21. concentrationThe filtrate was concentrated