Dimethyl Sulfoxide → 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

135 °C

A flask was charged with 4,6-dichloro-2-(propylthio)pyrimidin-5-amine (3 g), 2-(((3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol L-tartaric acid salt (5.1 g), dimethyl sulfoxide (30 mL) and triethyl amine (7.65 g). The mixture was heated to about 130-140° C. and maintained at the same temperature for about 7 hours and completion of the reaction was monitored by TLC. After completion of reaction the mixture was cooled to 25-30° C. followed by addition of water (30 mL) and toluene (30 mL). The mixture was stirred for about 10-15 minutes and layers were separated. The organic layer was sequentially washed with 5% aqueous sodium carbonate solution (30 mL), 5% aqueous acetic acid solution (30 mL) and sodium chloride solution (30 mL). The organic layer was separated and subjected to complete distillation under vacuum at 55-60° C. followed by cooling to room temperature and subsequent addition of n-hexane (45 mL). The mixture was stirred for about 11 hours at room temperature followed by isolation of solid by filtration and washing with n-hexane (10 mL). The solid isolated was subjected to drying under vacuum at 55-60° C. for about 90 minutes to afford the title compound in about 65% yield.

1. temperaturemaintained at the same temperature for about 7 hours
2. customAfter completion of reaction the mixture
3. temperaturewas cooled to 25-30° C.
4. customlayers were separated
5. washThe organic layer was sequentially washed with 5% aqueous sodium carbonate solution (30 mL), 5% aqueous acetic acid solution (30 mL) and sodium chloride solution (30 mL)
6. customThe organic layer was separated
7. distillationsubjected to complete distillation under vacuum at 55-60° C.
8. temperatureby cooling to room temperature
9. additionsubsequent addition of n-hexane (45 mL)
10. stirringThe mixture was stirred for about 11 hours at room temperature
11. filtrationfollowed by isolation of solid by filtration
12. washwashing with n-hexane (10 mL)
13. customThe solid isolated
14. customto drying under vacuum at 55-60° C. for about 90 minutes

ORD record

ord-1e1b75179e414264a8645ba9cf8b5c6d

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09233966B2