Triethylamine → 8-(2-Cyclopropyl-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-chloro-2-cyclopropyl-5-phenyl-thieno[2,3-d]pyrimidine (0.30 g, 1.05 mmol, ex Enamine), nortropinone hydrochloride (0.25 g, 1.57 mmol) and triethylamine (0.44 mL, 3.14 mmol) in ethanol (4 mL) was heated to 140° C. for 30 min in a microwave. Heating was repeated. Further portions of triethylamine (0.44 mL, 3.14 mmol) and nortropinone hydrochloride (0.25 g, 1.57 mmol) were added and the mixture was stirred at room temperature for 3 nights. It was diluted with ethyl acetate (20 mL) and water (20 mL). The layers were separated and the aqueous was extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with brine (1×20 mL), dried (magnesium sulfate, filtered and evaporated to give a brown oil (512 mg). This was purified by silica chromatography (10 g cartridge; eluent petroleum ether 40-60/ethyl acetate 0 to 100%; all output collected) to give 8-(2-cyclopropyl-5-phenyl-thieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-oneas a yellow solid (0.15 g). m/z [M+H]+ 376.0. Retention time 4.98 min (LCMS method+ve 6 min).

Provenance & Evidence