Triethylamine → 3-(6-chloro-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane

Participants

Reaction Conditions

Reaction Steps

A nearly homogeneous suspension of 2,4,6-trichloro-pyrimidine-5-carbaldehyde (example 1, Scheme 28, 2.1 g, 10 mmol) in dichloromethane/ethanol (8:2, 100 mL) was cooled to −78° C. in a dry-ice/acetone bath. Anhydrous hydrazine (0.31 mL, 10 mmol) was added in drops via syringe, followed by triethylamine (4 mL), also via dropwise addition. The cooling bath was removed and after one hour, the opaque maroon mixture was treated with 8-oxa-3-aza-bicyclo[3.2.1]octane hydrochloride (1.4 g, 9.4 mmol), followed by triethylamine (2 mL). The mixture was allowed to stir overnight. The maroon solid was collected by Buchner filtration, washed with ethanol, and then dried under house vacuum to give 3-(6-chloro-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (0.82 g, 31%). MS (ES+): 266.2, 268.2 (M+H)+

Provenance & Evidence