3-Butyn-1-OL → HCID 11754722, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (prepared as in Example 6, 729 mg, 1.5 mmol) in toluene (8 mL) was treated with N,N-diisopropylethylamine (2 mL), 4-hydroxybutyne (210 mg, 3.0 mmol), dichlorobis(triphenylphosphine)palladium(II) (60 mg), and copper(I) iodide (30 mg). The mixture was stirred at 25° C. overnight, and an oily black precipitate was obtained. The top clear solution was decanted, and the oily precipitate was rinsed first with toluene (5 mL) and then with hexanes (5 mL). The residue was dissolved in methylene chloride and extracted with methylene chloride and a 0.2N aqueous hydrochloric acid solution. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, elution with 1/1 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(4-hydroxy-but-1-ynyl)-pyrazin-2-yl]-propionamide (650 mg, 88.4%) as a fluffy solid: (ES)+-HRMS m/e calcd for C23H26ClN3O4S (M+H)+ 476.1406, found 476.1395.

Provenance & Evidence