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 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 1M 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 (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 1M 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 (10-30% EtOAc in hexanes)

ORD-Eintrag

ord-9792016fa3ba4c3bb4af1e91a1971a56

Quelldatensatz

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08575360B2