Pyridine → HCID 10368455, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 160 mg, 0.48 mmol) in methylene chloride (5 mL) and N,N-dimethylformamide (2 drops) was cooled to 5° C. and then treated with oxalyl chloride (90 μL, 1.03 mmol). After 5 min, the cooling bath was removed, and the stirring was continued for 15 min. The mixture was concentrated in vacuo to dryness, and the residue was further concentrated in vacuo to dryness from benzene (15 mL). The resulting acid chloride was dissolved in methylene chloride (10 mL), cooled to 5° C., and then treated with a solution of the 5-[1,3]dioxolan-2-ylmethylpyrazin-2yl-amine (0.49 mmol) and pyridine (100 μL, 1.23 mmol) in methylene chloride (5 mL). The mixture was stirred at 5° C. for 30 min then at 25° C. for 18 h. The mixture was diluted with methylene chloride (25 mL) and washed with a saturated aqueous sodium bicarbonate solution (20 mL), a 0.5M aqueous hydrochloric acid solution (20 mL), and a saturated aqueous sodium chloride solution (20 mL). Each aqueous layer was back-extracted with a small portion of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, gradient elution with ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-[1,3]dioxolan-2-ylmethyl-pyrazin-2-yl)-propionamide (112 mg, 47%) as a colorless foam: (ES)+-HRMS m/e calcd for C23H28ClN3O5S (M+H)+ 494.1511, found 494.1517.

Provenance & Evidence