Triethylamine → (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-[1-(5-iodo-pyrimidin-2-yl)-cyclopropylcarbamoyl]-cyclopropyl}-amide

Participants

Reaction Steps

To 1-amino-cyclopropanecarboxylic acid[1-(5-iodo-pyrimidin-2-yl)-cyclopropyl]-amide dihydrochloride (400 mg, 0.96 mmol) was added 1 mL of dry THF and triethylamine (0.71 ml, 3.98 mmol). Crude (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 chloride (476 mg, 1.0 mmol) was dissolved in 2 mL of dry THF and transferred to the reaction flask. After 2 h, the solvent was removed at 55° C. under a stream of N2. The resulting slurry was diluted with EtOAc (75 mL) and washed with 10% aq citric acid (75 mL) and saturated aq NaHCO3 (75 mL). The organic layer was dried over Na2SO4 and concentrated to give a light orange foam. This solid was purified by normal phase flash chromatography on silica gel (1→3% MeOH/CH2Cl2) to give 767 mg of the title compound as a tan powder, m/z 785.5.

Provenance & Evidence