2,6-Lutidine → HCID 10027991, 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, 250 mg, 0.76 mmol) in methylene chloride (5 mL) was cooled to 0° C. and then was treated with a 2.0M solution of oxalyl chloride in methylene chloride (435 μL, 0.87 mmol) and N,N-dimethylformamide (1 drop). The reaction mixture was stirred at 0° C. for 30 min and then concentrated in vacuo. The resulting oil was dissolved in tetrahydrofuran (2 mL) at 25° C. and then was treated dropwise with a solution of the inseparable mixture of 5-(tetrahydro-furan-2-yl)-pyridin-2-ylamine and 2-aminopyridine (224 mg, 1.36 mmol) and 2,6-lutidine (263 μL, 2.27 mmol) in tetrahydrofuran (3 mL) via an addition funnel. The resulting cloudy solution was then stirred overnight for 16 h at 25° C. After this time, the reaction was diluted with water (10 mL) and then extracted with methylene chloride (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 65/35 to 50/50 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(tetrahydro-furan-2-yl)-pyridin-2-yl]-propionamide (86 mg, 24%) as a white foam: (ES)+-HRMS m/e calcd for C24H29ClN2O4S (M+H)+ 477.1610, found 477.1616.

Provenance & Evidence