Diisopropylethylamine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(4-hydroxy-tetrahydropyran-4-yl-ethynyl)-pyrazin-2-yl]-propionamide

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, 486 mg, 1.0 mmol) in toluene (8 mL) was treated with N,N-diisopropylethylamine (2 mL), 4-ethynyl-tetrahydropyran-4-ol (prepared as in Example 46, 252 mg, 2.0 mmol), copper(I) iodide (20 mg), and dichlorobis(triphenylphosphine)palladium(II) (40 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, 2/1 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(4-hydroxy-tetrahydropyran-4-yl-ethynyl)-pyrazin-2-yl]-propionamide (474 mg, 89.30%) as a fluffy solid: (ES)+-HRMS m/e calcd for C23H30ClN3O4S (M+H)+ 532.1668, found 532.1675.

Provenance & Evidence