反应详情

To a solution 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}-cyclopropane-carboxylic acid (1.21 g, 2.32 mmol), HATU (970 mg, 2.55 mmol) and diisopropyl-ethylamine (808 μL, 4.64 mmol) in DMF (4 mL) was added 1-(5-iodo-pyridin-2-yl)-cyclopropylamine (724 mg, 2.78 mmol). The mixture was stirred for 1.5 h and then diluted with EtOAc (30 mL). The layers were separated and the organic layer was washed with water (3×30 mL) and brine (1×25 mL), dried with MgSO4, filtered, and concentrated to afford a crude solid. The crude material was purified by flash chromatography on silica gel, eluting with 50% hexanes in ethyl acetate (and increasing polarity to 75% ethyl acetate) to afford 1.60 g of the title compound:

1. customThe layers were separated
2. washthe organic layer was washed with water (3×30 mL) and brine (1×25 mL)
3. dry with materialdried with MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customto afford a crude solid
7. customThe crude material was purified by flash chromatography on silica gel
8. washeluting with 50% hexanes in ethyl acetate (and increasing polarity to 75% ethyl acetate)