4-Methylpyrazole → 4-[3'-Fluoro-5'-(4-methyl-pyrazol-1-ylmethyl)-2,3,5,6-tetrahydro-[1,2]bipyridinyl-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

Participants

Reaction Conditions

Reaction Steps

Mesyl chloride (96 μL, 1.2 mmol) was added to an ice cooled solution of 53-1 (0.25 g, 0.62 mmol) and triethylamine (0.26 mL, 1.9 mmol) in 5 mL of DCM. After 2 h, the mixture was diluted with DCM (30 mL), washed with brine (15 mL) and water (15 mL), dried and concentrated under vacuum. The residue was taken up in DMF and added to a mixture of 4-methyl-1H-pyrazole (0.8 mmol) and sodium hydride (30 mg, 60%, 0.8 mmol) in DMF which had been pre-stirred for 5 minutes. The mixture was heated to 100° C. for 2 h then allowed to cool down to room temperature, diluted with water (1.5 mL) and extracted with DCM (2 mL). The organic layer was concentrated under a stream of nitrogen, the residue was taken up in methanol and the mixture was purified by HPLC to afford 54-1: LC-MS 473.2 (MH+).

Provenance & Evidence