2,6-Lutidine → HCID 67482886, 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, 170 mg, 0.51 mmol) in methylene chloride (10 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (385 μL, 0.77 mmol) and catalytic N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 30 min and at 25° C. for 2 h. The solution was then concentrated in vacuo. The residue was dissolved in methylene chloride (10 mL), cooled to 0° C., and then treated with a solution of 2-(5-amino-pyrazin-2-yl)-malonic acid diethyl ester (130 mg, 0.51 mmol) and 2,6-lutidine (120 μL, 1.03 mmol) in tetrahydrofuran (10 mL). The reaction mixture was then stirred at 0° C. for 15 min and at 25° C. for 16 h. The reaction was then concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 1/1 ethyl acetate/hexanes) afforded the 2(R)-{5-[2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazin-2-yl}-malonic acid diethyl ester (76.9 mg, 26%) as a pale yellow oil. This material was further purified by dissolving it in methylene chloride and washing with a 1N aqueous hydrochloric acid solution (25 mL). The organic layer was then dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the 2(R)-{5-[2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazin-2-yl}-malonic acid diethyl ester (51.3 mg, 18%) as a pale yellow oil: (ES)+-HRMS m/e calcd for C26H32ClN3O7S (M+H)+ 566.1722, found 566.1726.

Provenance & Evidence