Acetic Acid → HCID 69478876, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 40.0 g (95.1 mmol) of 9-[(3aR,4R,6S,6aS)-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-chloro-9H-purine and 9.52 g (95.1 mmol) of CaCO3 powder was successively added 200 mL of glacial acetic acid and 21.1 mL (190 mmol) of 4-chloro-2-fluoroaniline at ambient temperature under nitrogen. The light brown mixture was heated at 76° C. for 1.5 to 2.0 h. The mixture was cooled to below 30° C. and diluted with 200 mL of toluene. The mixture was concentrated to about 120 mL by distillation at 35-45° C. under vacuum below 50 torr. This azeotropic process was repeated with a second charge of 240 mL of toluene and distilled to about 200 mL. The above mixture was filtered by suction and the filtrate was concentrated to about 80 mL at 35-45° C. under vacuum to provide a toluene solution of crude product of N-{9-[(3aR,6S,6aS)-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-2,2-dimethyltetrahydrofuro [3,4-d][1,3]dioxol-4-yl]-9H-purin-6-yl}N-(4-chloro-2-fluorophenyl)amine.

Provenance & Evidence