反应详情

To a mixture of 0.265 g (0.59 mmole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-22), 0.2256 g (0.59 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 8 mL of dichloromethane, 0.25 mL of triethylamine was added followed by 0.1181 g (0.59 mmole) of 4-amino-piperidine-1-carboxylic acid tert-butyl ester. After stirring overnight, 16 mL of dichloromethane, 14 mL of water and 0.8 mL of 1M sodium hydroxide was added. The dichloromethane layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with hexanes-ethyl acetate (gradient, 40:60-10:90) to give 0.2278 g of 4-[4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoylamino]-piperidine-1-carboxylic acid tert-butyl ester.

1. additionwas added
2. dry with materialThe dichloromethane layer was dried over anhydrous magnesium sulfate
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by silica gel chromatography
6. washeluting with hexanes-ethyl acetate (gradient, 40:60-10:90)