Dimethyl Sulfoxide → N-[(S)-1,2-dioxo-1-[N-[(S)-2-oxocyclohexyl]-amino]-3-heptyl]-1-[N-(morpholine-4-carbonyl)amino]cyclohexanecarboxamide

Temperature

0 °C

Under nitrogen stream, at 0° C., 1.45 g (11.2 mmol) of N,N-diisopropylethylamine was added dropwise to a mixed solution of anhydrous dimethylsulfoxide (5 ml) and anhydrous dichloromethane (5 ml) containing 1.78 g (11.2 mmol) of sulfur trioxide pyridine complex salt. Moreover, to the mixture was added an anhydrous dichloromethane (5 ml) solution containing 465 mg (0.94 mmol) of N-[(2S,3S)-2-hydroxy-1-[N-[(1S,2S)-2-hydroxycyclohexane-1-yl]amino]-1-oxo-3-heptyl]-1-[N-(morpholine-4-carbonyl)amino]cyclohexanecarboxamide, and the resulting mixture was stirred at 0° C. for 3 hours. After completion of the reaction, ice-water was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed successively with a 10% aqueous citric acid solution, a saturated aqueous sodium hydrogen carbonate solution and a saturated NaCl solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by neutral silica gel column chromatography to obtain 402 mg (Yield: 87%) of the title compound.

1. additioncontaining 1.78 g (11.2 mmol) of sulfur trioxide pyridine complex salt
2. additionwas added to the reaction mixture
3. extractionthe resulting mixture was extracted with ethyl acetate
4. washThe organic layer was washed successively with a 10% aqueous citric acid solution
5. dry with materiala saturated aqueous sodium hydrogen carbonate solution and a saturated NaCl solution, dried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by neutral silica gel column chromatography

ORD record

ord-23e64c85d1694678a1ef4879dcf8fbf8

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07326799B2