2-Fluorobenzoyl chloride → N-(7-(cyclopropylamino)-3-formylpyrazolo[1,5-a]pyrimidin-5-yl)-2-fluorobenzamide

Participants

Reaction Steps

To 5-amino-7-(cyclopropylamino) pyrazolo[1,5-a]pyrimidine-3-carbaldehyde (step b) (30 mg, 0.138 mmol) in 1.0 mL tetrahydrofuran, stirring under nitrogen, was added 2-fluoro benzoyl chloride (33 ul, 0.275 mmol) and DIPEA (28.8 ul). The reaction mixture was stirred at room temperature for one hour. The reaction was then partitioned between ethyl acetate and water, the organic layer was dried under sodium sulfate concentrated on high vacuum to yield N-(7-(cyclopropylamino)-3-formylpyrazolo[1,5-a]pyrimidin-5-yl)-2-fluorobenzamide. The crude product was further dissolved in 1.0 mL ethanol, added hydantoin (41.2 mg, 0.411 mmol) and pipperdine (40.0 ul). The reaction was heated to 80° C. for three hours. Cooled the reaction mixture and yellow precipitate was filtered, washed with ethanol to yield 10 mg (40% yield, two steps) (Z)-N-(7-(cyclopropylamino)-3-((2,5-dioxoimidazolidin-4-ylidene)methyl)pyrazolo[1,5-a]pyrimidin-5-yl)-2-fluorobenzamide. LCMS (M+1=422)

Provenance & Evidence