1H-1,2,4-Triazole → 1-{[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-1,2,4-triazol-1-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid allyl ester

Participants

Reaction Steps

An 8-mL vial was charged with 1-{[(R)-7-(3,5-dichloro-phenyl)-5-(4-iodo-benzyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid allyl ester (251 mg, 0.377 mmol), 1,2,4-triazole (39 mg, 0.57 mmol), and (1R,2R)—N,N′-dimethyl-cyclohexane-1,2-diamine (16 mg, 0.11 mmol), K3PO4 (160 mg, 0.76 mmol), and 0.5 mL of DMF. The vial was purged with N2 and sealed with a screw cap. The green reaction mixture was heated at reflux for 20 h. The reaction mixture was cooled to room temperature, diluted with 3 mL of EtOAc, and filtered through a small plug of Celite, washing with 20 mL of ethyl acetate. The filtrates were washed with 3×10 mL of water and 10 mL of brine, dried over Na2SO4, filtered, and concentrated. The crude was purified by flash chromatography on silica gel (20 g, 0-3% MeOH/CH2Cl2) to provide 109 mg (48%) of 1-{[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-1,2,4-triazol-1-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid allyl ester as a pale orange foam.

Provenance & Evidence