Pyridine → HCID 66559575, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-formyloxy-cyclopentyl)-propionic acid (380 mg, 1.01 mmol) in toluene (10 mL) at 0° C. was treated with N,N-dimethylformamide (0.008 mL) followed by a 2.0M solution of oxalyl chloride in methylene chloride (0.75 mL). The reaction mixture was allowed to stir at 0° C. for 30 min and at 25° C. for 1.5 h. It appeared that a thick oil in the bottom of the reaction flask never solubilized. Additional methylene chloride (10 mL) was added at 25° C. followed by N;N-dimethylformamide (0.002 mL) and oxalyl chloride (0.3 mL). The reaction mixture was stirred at 25° C. for an additional 45 min and then concentrated in vacuo. The residue was dissolved in dry tetrahydrofuran (5 mL) and cooled to 0° C. This cold solution was then treated with a solution of 2-aminopyrazine (142 mg, 1.5 mmol) and pyridine (0.121 mL, 1.5 mmol) in dry tetrahydrofuran (5 mL) via a cannula. The resulting reaction mixture was stirred at 0° C. for 1 h and then diluted with methylene chloride (100 mL). The organic layer was successively washed with a 1M aqueous citric acid solution (2×100 mL), a saturated sodium bicarbonate solution 1×100 mL), and a saturated sodium chloride solution 1×100 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford formic acid 3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-2-(pyrazin-2-ylcarbamoyl)-ethyl]-cyclopentyl ester (375 mg, 82%) as an off-white solid.

Provenance & Evidence