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

Participants

Reaction Conditions

Reaction Steps

A flask was charged with 4,6-dichloro-2-(propylthio)pyrimidin-5-amine (50 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 (84.83 g), dimethyl sulfoxide (500 mL) and triethyl amine (127.5 g). The mixture was heated to about 95-105° 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 25-30° C. followed by addition of water (1000 mL) and toluene (600 mL). The mixture was stirred for about 10 minutes and layers were separated. The organic layer was sequentially washed with 20% aqueous sodium carbonate solution (1000 mL), 20% aqueous acetic acid solution (1000 mL) and water (700 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-hexane (800 mL). The mixture was stirred for about 9 hours at room temperature followed by isolation of solid by filtration and washing with n-hexane (100 mL). The solid isolated was subjected to drying under vacuum at 55-60° C. for about 5 hours to afford the title compound in about 84% yield having HPLC purity of about 98%.

Provenance & Evidence