2,6-Lutidine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-furan-2-yl-pyrazin-2-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 125 mg, 0.38 mmol) in methylene chloride (2.5 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (217 μL, 0.43 mmol) and N,N-dimethylformamide (1 drop). The reaction mixture was stirred at 0° C. for 30 min, concentrated in vacuo, and azeotroped with toluene (2 mL) two times. The resulting oil was then dissolved in tetrahydrofuran (1 mL) at 25° C. This solution was then treated dropwise with 5-furan-2-yl-pyrazin-2-ylamine (91 mg, 0.57 mmol) and 2,6-lutidine (66 μL, 0.57 mmol) in tetrahydrofuran (1.5 mL) via an addition funnel. The resulting cloudy solution was then stirred overnight for 16 h at 25° C. After this time, the reaction was diluted with water (10 mL) and then extracted with methylene chloride (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 80/20 to 60/40 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-furan-2-yl-pyrazin-2-yl)-propionamide (124 mg, 69%) as a yellow foam: (ES)+-HRMS m/e calcd for C23H24ClN3O4S (M+H)+ 474.1249, found 474.1254.

Provenance & Evidence