Acetic Acid → (R)-ethyl 1-(2-(1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidine-3-carboxylate

Participants

Reaction Steps

Acetic acid (4.3 g, 67.2 mmol) was added to a solution of (R)-ethyl 1-(5,6-diaminopyridin-2-yl)piperidine-3-carboxylate (890 mg, 3.36 mmol), ethyl 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarbimidate (445 mg, 1.78 mmol) and triethylamine (0.8 mL, 5.92 mmol) in ethanol (25 mL) at room temperature under a nitrogen atmosphere. The mixture was heated at reflux for 16 h, then was concentrated under reduced pressure. The resulting residue was partitioned between ethyl acetate and water. The organics were dried over sodium sulfate and concentrated under reduced pressure. The crude material was purified via column chromatography (100-200 mesh silica gel, 20-60% ethyl acetate in petroleum ether) to afford (R)-ethyl 1-(2-(1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidine-3-carboxylate (600 mg). MS (ES+) (M+H) 415.2859.

Provenance & Evidence