2,6-Lutidine → N-[5-(1-tert-butoxyimino-ethyl)-pyrazin-2-yl]-3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2(R)-(4-methanesulfonylphenyl)-propionic acid (prepared as in Example 3, 500.0 mg, 1.687 mmol) in methylene chloride (4.2 mL) was cooled to 0° C. The reaction mixture was treated with N,N-dimethylformamide (1 drop) and oxalyl chloride (294 μL, 3.374 mmol). The reaction mixture was stirred at 0° C. for 15 min and then slowly allowed to warm to 25° C. where it was stirred for 3 h. The solution was then concentrated in vacuo. The resulting residue was dissolved in methylene chloride (8.4 mL) and then cooled to 0° C. This cooled solution was then treated dropwise with a solution of 1-(5-amino-pyrazin-2-yl)-ethanone O-tert-butyl-oxime (prepared as in Example 28, 351.4 mg, 1.687 mmol) and 2,6-lutidine (246 μL, 2.109) in tetrahydrofuran (8.4 mL). The reaction mixture was stirred at 0° C. for 30 min and then was allowed to warm to 25° C. where it was stirred overnight. The reaction mixture was then concentrated in vacuo, diluted with ethyl acetate (250 mL), and washed with a 1N aqueous hydrochloric acid solution (3×100 mL) and a saturated aqueous sodium chloride solution (1×300 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 1/4 ethyl acetate/hexanes) afforded the N-[5-(1-tert-butoxyimino-ethyl)-pyrazin-2-yl]-3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-propionamide (451.1 mg, 55%) as a yellow foam. This material was re-purified via Biotage chromatography (FLASH 40L, Silica, 5% ethyl acetate/methylene chloride) to afford N-[5-(1-tert-butoxyimino-ethyl)-pyrazin-2-yl]-3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-propionamide (380.4 mg, 46%) as a white foam: mp 81–83° C. (foam to gel); (ES)+-HRMS m/e calcd for C25H34N4O4S (M+H)+ 487.2374, found 487.2377.

Provenance & Evidence