2,6-Lutidine → HCID 10029454, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(4-methylsulfonyl-3-trifluoromethyl-phenyl)-3-(tetrahydro-pyran-2-yl)-propionic acid (prepared as in Example 12, 300 mg, 0.79 mmol) in methylene chloride (6 mL) was treated with N,N-dimethylformamide (7 drops) and then cooled to 0° C. The reaction mixture was then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.48 mL, 0.95 mmol). The reaction mixture was stirred at 0° C. for 30 min, allowed to warm to 25° C., and then concentrated in vacuo to remove solvents and excess oxalyl chloride. The resulting residue was re-dissolved in dry tetrahydrofuran (6 mL) and was treated dropwise with a solution of 6-aminonicotinic acid methyl ester (252 mg, 1.67 mmol) in tetrahydrofuran (5 mL) and 2,6-lutidine (0.48 mL, 3.95 mmol). The resulting reaction mixture was stirred at 25° C. for 16 h. The reaction mixture was then diluted with water (100 mL) and extracted with methylene chloride 3×50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 7/3 hexanes/ethyl acetate to 1/1 hexanes/ethyl acetate) afforded 6-[2-(4-methylsulfonyl-3-trifluoromethyl-phenyl)-3-(tetrahydro-pyran-2-yl)-propionylamino]-nicotinic acid methyl ester (227 mg, 55%) as a white foam: EI-HRMS m/e calcd for C23H25F3N2O6S (M+H)+ 537.1277. found 537.1284.

Provenance & Evidence