4-Fluoroaniline → (+/-)-1-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Participants

Reaction Conditions

Reaction Steps

(±)-1-[trans-3-(tert-Butyl-dimethyl-silanyloxy)-cyclopentyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (125 mg, 0.25 mmol) (from Example 39b supra) was suspended in 2-propanol (3 mL) (Fisher). 4-Fluoroaniline (0.036 mL, 0.38 mmol) (Aldrich) and p-toluenesulfonic acid mono-hydrate (12.5 mg, 0.05 mmol) (Aldrich) were added and the mixture was heated to 160° C. in a microwave synthesizer (SmithSynthesizer®) for 30 minutes. After cooling to room temperature, the heterogeneous reaction mixture was diluted with dichloromethane. The resulting solution was washed with 1 N aqueous hydrochloric acid. The layers were separated and the organic phase was dried over anhydrous sodium sulfate, filtered and then concentrated under reduce pressure to give (±)-1-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-3-(4-ethyl-phenyl)-7-(4-fluoro-phenylamino)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a pale green solid. (Yield 123 mg, 85%).

Provenance & Evidence