1,2-Dichloroethane → N-(3'-hydroxybiphenyl-2-ylmethyl)-2-[3-(4-cyano-3-fluorobenzyl)-3H-imidazol-4-yl]acetamide

Participants

Reaction Steps

A solution of lithium 1-(4-cyano-3-fluorobenzyl)imidazol-5-ylacetate from Step D (143 mg, 0.55 mmol), 2-aminomethyl-3′-hydroxybiphenyl hydrochloride from Example 4, Step H (118 mg, 0.50 mmol), 1-hydroxybenzotriazole hydrate (74 mg, 0.55 mmol), EDC (105 mg, 0.55 mmol), and diisopropylethylamine (129 mg, 1.00 mmol) in dry, degassed DMF (2 mL) was stirred at ambient temperature overnight. The solvent was removed under reduced pressure and the residue was partitioned between sat. aq. NaHCO3 (3 mL) and CHCl3 (5 mL). The aqueous layer was extracted further with CHCl3 (2×5 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography, eluting with a gradient of 3-5% MeOH/0.3-0.5% NH4OH in CHCl3 to give the titled product as a white foam.

Provenance & Evidence