Hydrochloric Acid → 1-Cyclopentyl-7-(4-diethylamino-butylamino)-3-(2,6-difluoro-3-hydroxy-5-methoxy phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a solution of sodium ethylthiolate [generated from sodium hydride (200 mg, 8.32 mmol) and ethanethiol (616 μL, 8.32 mmol) in dimethylformamide (20 mL)], 1-Cyclopentyl-7-(4-diethylamino-butylamino)-3-(2,6-difluoro-3,5-dimethoxy-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one in dimethylformamide (8 mL) was added. The resulting solution was then stirred at 75° C. for 90 minutes. The solvent was removed under reduced pressure to afford a light brown oil. Dichloromethane (100 mL) and water (20 mL) were added. The bilayer thus afforded was then stirred vigorously while 4 N hydrochloric acid was added. Enough hydrochloric acid was added until the aqueous layer reached pH=5. The layers were separated; the aqueous layer was extracted with dichloromethane (2×80 mL). The organic layers were combined and set aside. Saturated aqueous sodium chloride (20 mL) was to the aqueous layers and was extracted with ethyl acetate (2×80 mL). The organic layers were combined, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. To the yellow oil (794 mg) thus afforded, hexanes were added to remove non-polar impurities. The supernatant was removed, and the remaining residue was placed in vacuo. The oil was purified via reverse phase HPLC to give the title compound (289 mg, 54%) as a clear amber gum: MS (APCI) 519.2, 520.2.

Provenance & Evidence