Diisopropylethylamine → (R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid{1-[(R)-1-(5-bromo-pyridin-2-yl)-ethylcarbamoyl]-cyclopropyl}-amide

Participants

Reaction Steps

A suspension of 1-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid, (500 mg, 0.92 mmol), (R)-1-(5-bromo-pyridin-2-yl)-ethylamine dihydrochloride (303 mg, 1.11 mmol) and diisopropylethylamine (0.640 mL, 3.69 mmol) in 4 mL of DMF was stirred at room temperature for 10 min HATU (386 mg, 1.01 mmol) was added, and the clear yellow reaction mixture was stirred at room temperature for 3 h. The reaction mixture was partitioned between 75 mL of ethyl acetate and 25 mL of water. The organic phase was washed with 2×25 mL of 5% aqueous NaCl solution and 25 mL of brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel, eluting with 0-3% MeOH in CH2Cl2, to provide 653 mg (98%) of title compound as a yellow foam, m/z 726.4 [M+1]+.

Provenance & Evidence