Pyridine → 2-(R)-(3-chloro-4-methanesulfonylphenyl)-3-cyclopentyl-N-(5-dimethoxymethylpyrazin-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, 883 mg, 2.67 mmol) and oxalyl chloride (677 mg, 5.34 mmol) in methylene chloride/toluene (1:1, 5 mL) was treated with N,N-dimethylformamide (2 drops) at 25° C. The reaction mixture was stirred at 25° C. for 2 h. The solution was concentrated in vacuo, and the residue was concentrated three times from toluene (5 mL). The residue was suspended in tetrahydrofuran (5 mL) at 0° C. and then treated with a mixture of 5-dimethoxymethyl-pyrazin-2-ylamine (451 mg, 2.67 mmol) and pyridine (0.216 mL, 2.67 mmol) in tetrahydrofuran (5 mL) over 5 min. At this time, the reaction was allowed to warm to 25° C. where it stirred for 18 h. The resulting mixture was partitioned between ethyl acetate (50 mL) and a dilute aqueous ammonium chloride solution (50 mL). The aqueous layer was separated. The organic layer was sequentially washed with water (1×25 mL), a saturated aqueous sodium bicarbonate solution (1×25 mL), water (1×25 mL), an aqueous copper(II) sulfate solution (1×25 mL), and a saturated aqueous sodium chloride solution (1×25 mL). The organic layer was then dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 2/3 ethyl acetate/hexanes) afforded the 2-(R)-(3-chloro-4-methanesulfonylphenyl)-3-cyclopentyl-N-(5-dimethoxymethylpyrazin-2-yl)-propionamide (890 mg, 69%) as a pale yellow foam: (ES)+-HRMS m/e calcd for C22H28ClN3O5S (M+H)+ 424.0729, found 424.0733.

Provenance & Evidence