反应详情

温度

50 °C

A solution of 6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one (for example, as prepared for Reference Example 1) (1.46 g, 3.74 mmol) in isopropyl alcohol (14.6 mL, 10 vols) was clarified (filtered at room temperature through a BondElut cartridge) and then heated to approximately 50° C. A solution of maleic acid (0.434 g, 3.74 mmol) in isopropyl alcohol (2.9 mL, 2 vols) was added. The resulting solution was then seeded and cooled to 45° C. Further seed was added. The resulting slurry was cooled to room temperature and held overnight (approximately 16 hours), then cooled in an ice/water bath for 30 minutes. The slurry was filtered, washing with isopropyl alcohol (4.5 mL, 3 vols and then 3 mL, 2 vols). The product was dried under reduced pressure at 40° C. to constant weight to give 6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one, maleate salt (1.305 g, 69% th).

1. filtrationfiltered at room temperature through a BondElut cartridge) and
2. temperaturecooled to 45° C
3. additionFurther seed was added
4. temperatureThe resulting slurry was cooled to room temperature and held overnight (approximately 16 hours)
5. temperaturecooled in an ice/water bath for 30 minutes
6. filtrationThe slurry was filtered
7. washwashing with isopropyl alcohol (4.5 mL, 3 vols
8. customThe product was dried under reduced pressure at 40° C. to constant weight