tert-butyl 4-[3-((3R)-3-{[(1S)-1-(5-bromopyridin-3-yl)-3-tert-butoxy-3-oxopropyl]carbamoyl}piperidin-1-yl)-3-oxopropyl]piperidine-1-carboxylate → tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[3-(2-fluoroethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Participants

Reaction Steps

To a degassed solution of tert-butyl 4-[3-((3R)-3-{[(1S)-1-(5-bromopyridin-3-yl)-3-tert-butoxy-3-oxopropyl]carbamoyl}piperidin-1-yl)-3-oxopropyl]piperidine-1-carboxylate (example 27c, 100 mg, 15 mmol), copper iodide (4.4 mg, 23 μmol) and tetrakis(triphenylphosphine) palladium(0) (18 mg, 15 μmol) in DMF (0.4 mL) and n-butyl amine (0.23 mL) was added a solution of 1-ethynyl-3-(2-fluoroethoxy)benzene (50 mg, 0.31 mmol) in DMF (0.6 mL) over 60 minutes at 100° C. After additional 20 minutes at 100° C. the mixture was diluted with DMSO and purified by preparative HPLC to yield 90 mg of tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[3-(2-fluoroethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

Provenance & Evidence