Isoamyl Alcohol → 2-(((3aR,4S,6R,6aS)-6-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol

Temperature

105 °C

A flask was charged with 2-(((3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol L-tartaric acid salt (17 g), sodium bicarbonate (21.2 g), 4,6-dichloro-2-(propylthio)pyrimidin-5-amine (10 g) and isoamyl alcohol (30 mL). The mixture was heated to about 100-110° C. and maintained at the same temperature for about 10-12 hours and completion of the reaction was monitored by TLC. After completion of reaction the mixture was cooled to room temperature then filtered and the bed was washed with isoamyl alcohol (10 mL). The filtrate was subjected to complete distillation under vacuum at about 65-70° C. to afford the crude. Then water (100 mL) and toluene (100 mL) were charged. The mixture was stirred for about 20 minutes and layers were separated. The organic layer was separated and washed with water (100 mL). The organic layer was separated and subjected to complete distillation under vacuum at 60-65° C. followed by cooling to room temperature and subsequent addition of n-heptane (150 mL). The mixture was stirred for about 4-5 hours followed by isolation of solid by filtration and washing with n-heptane (20 mL). The solid isolated was subjected to drying under vacuum at 50-55° C. to afford the title compound in about 82% yield having HPLC purity of about 99%.

1. temperaturemaintained at the same temperature for about 10-12 hours
2. customAfter completion of reaction the mixture
3. temperaturewas cooled to room temperature
4. filtrationthen filtered
5. washthe bed was washed with isoamyl alcohol (10 mL)
6. distillationThe filtrate was subjected to complete distillation under vacuum at about 65-70° C.
7. customto afford the crude
8. customlayers were separated
9. customThe organic layer was separated
10. washwashed with water (100 mL)
11. customThe organic layer was separated
12. distillationsubjected to complete distillation under vacuum at 60-65° C.
13. temperatureby cooling to room temperature
14. additionsubsequent addition of n-heptane (150 mL)
15. stirringThe mixture was stirred for about 4-5 hours
16. filtrationfollowed by isolation of solid by filtration
17. washwashing with n-heptane (20 mL)
18. customThe solid isolated
19. customto drying under vacuum at 50-55° C.

ORD record

ord-de318d2e9fff4de0a4264f0fb57718c6

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09233966B2