Diisopropylethylamine → 6-[3-Cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionylamino]-nicotinic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionic acid (prepared as in Example 87, 202 mg, 0.66 mmol), benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (294 mg, 0.66 mmol), and 6-amino-nicotinic acid methyl ester (111 mg, 0.73 mmol) in N,N-dimethylformamide (3.32 mL) at 25° C. was treated with N,N-diisopropylethylamine (0.24 mL, 1.39 mmol). The reaction mixture was stirred at 25° C. for 12 h. At this time, the reaction was poured into water (50 mL) and extracted into ethyl acetate (3×35 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 80/20 hexanes/ethyl acetate) afforded 6-[3-cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionylamino]-nicotinic acid methyl ester (36.7 mg, 12.6%) as a white foam: EI-HRMS m/e calcd for C22H22F4N2O3 (M+) 438.1566, found 438.1568.

Provenance & Evidence