反应详情

6-Chloro-8-(3-fluorophenyl)-9-methyl-9H-2-purinyl-amine (960 g) was dissolved in 9.6 liters of tetrahydrofuran and then 774.3 g of cuprous iodide and 1.49 liters of diiodomethane were added thereto. Isoamyl nitrite (1.49 liters) was added dropwise during 1 hour into the mixture with heating under reflux. The reaction solution was heated under reflux for 15 minutes, cooled, diluted with 4 liters of ethyl acetate and then filtered through Celite followed by washing with ethyl acetate three times (3×2 liters). The filtrate and the washings were combined and washed with 8 liters of water and 8 liters of brine. The organic layer was dried over 2 kg of anhydrous sodium sulfate and concentrated to about 3 liters. The concentrated solution was diluted with 10 liters of hexane and the resulting crystals were filtered and washed with 1 liter of hexane. The crystals were then dried at 50° C. for 4 hours to give 1076 g of 6-chloro-8-(3-fluorophenyl)-2-iodo-9-methyl-9H-purine. The yield was 75%.

1. temperaturewith heating
2. temperatureunder reflux
3. temperatureThe reaction solution was heated
4. temperatureunder reflux for 15 minutes
5. temperaturecooled
6. filtrationfiltered through Celite
7. washby washing with ethyl acetate three times (3×2 liters)
8. washwashed with 8 liters of water and 8 liters of brine
9. dry with materialThe organic layer was dried over 2 kg of anhydrous sodium sulfate
10. concentrationconcentrated to about 3 liters
11. additionThe concentrated solution was diluted with 10 liters of hexane
12. filtrationthe resulting crystals were filtered
13. washwashed with 1 liter of hexane
14. customThe crystals were then dried at 50° C. for 4 hours