6-(2-Biphenyl-4-yl-3-cyclopentyl-propionylamino)-nicotinic acid methyl ester → 2-biphenyl-4-yl-3-cyclopentyl-N-(5-hydroxymethyl-pyridin-2-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 6-(2-biphenyl-4-yl-3-cyclopentyl-propionylamino)-nicotinic acid methyl ester (prepared in Example 22, 100 mg, 0.23 mmol) in diethyl ether (3 mL) at 0° C. under nitrogen was slowly treated with lithium aluminum hydride powder (12 mg, 0.30 mmol). The resulting reaction mixture continued to stir at 0° C. and was allowed to gradually warm to 25° C. The reaction mixture was then stirred at 25° C. over a period of 64 h. The reaction mixture was slowly quenched by the dropwise addition of water (5 mL). The resulting reaction mixture was partitioned between water and ethyl acetate, and the layers were separated. The aqueous layer was further extracted with ethyl acetate (1×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/2 hexanes/ethyl acetate) afforded 2-biphenyl-4-yl-3-cyclopentyl-N-(5-hydroxymethyl-pyridin-2-yl)-propionamide (33 mg, 36%) as a white solid: mp 67-70° C.; EI-HRMS m/e calcd for C26H28N2O2 (M+) 400.2151, found 400.2147.

Provenance & Evidence