Propargyl alcohol → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-hydroxy-prop-1-ynyl)-pyrazin-2-yl]-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (prepared as in Example 6, 486 mg, 1 mmol) and propargyl alcohol (84 mg, 1.5 mmol) in toluene (6 mL) was treated with copper(I) iodide (19.2 mg, 0.10 mmol), dichlorobis(triphenylphosphine)palladium(II) (36 mg, 0.05 mmol), and N,N-diisopropylethylamine (2 ml). The resulting mixture was stirred at 25° C. for 1 h and was then heated to 60° C. for 1 h. At this time, the reaction was concentrated in vacuo. The residue was extracted into ethyl acetate from a 1N aqueous hydrochloric acid solution. The combined organic layers were washed with a saturated aqueous sodium chloride solution, dried, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/1 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-hydroxy-prop-1-ynyl)-pyrazin-2-yl]-propionamide (275 mg, 57%) as a pale yellow solid: (ES)+-HRMS m/e calcd for C22H24ClN3O4S (M+H)+ 462.1249, found 462.1252.

Provenance & Evidence