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

To a suspension of (R)-5-(4-bromo-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid (1.00 g, 2.02 mmol) and 1-amino-cyclopropanecarboxylic acid allyl ester hydrochloride (430 mg, 2.42 mmol) in 6 mL of DMF at room temperature was added diisopropylethylamine (1.05 mL, 6.06 mmol), and the reaction mixture (became mostly clear) was stirred for 10 min. HATU (845 mg, 2.22 mmol) was then added, and the clear yellow reaction mixture was stirred at room temperature for 21 h. The reaction mixture was partitioned between 150 mL of ethyl acetate and 50 mL of 1 M HCl. The organic phase was washed with satd. NaHCO3 solution, water (2×), and brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography on silica gel (50 g, 10-30% EtOAc in hexanes), to furnish 1.16 g of 1-{[(R)-5-(4-bromo-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid allyl ester (93%) as a colorless foam.

1. stirringthe clear yellow reaction mixture was stirred at room temperature for 21 h
2. customThe reaction mixture was partitioned between 150 mL of ethyl acetate and 50 mL of 1 M HCl
3. washThe organic phase was washed with satd
4. dry with materialNaHCO3 solution, water (2×), and brine, dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by flash chromatography on silica gel (50 g, 10-30% EtOAc in hexanes)

ORD record

ord-f308db14ba16407aa3fd6e7abdd7cf30

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08552205B2