反应详情

A solution of 1,1-dimethylethyl ((3R,45)-1-{(2R/S)-2-[3-chloro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-hydroxypropyl}-3-hydroxy-4-piperidinyl)carbamate (8.75 g, 18.7 mmol) and diisopropylethylamine (4.9 ml) in dichloromethane (90 ml) was treated at 0° C. under argon with para-toluenesulphonic anhydride (6.7 g, 20.6 mmol). After 3 hours at room temperature more para-toluenesulphonic anhydride (0.7 g) was added. After 2.5 days the mixture was washed with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted with dichloromethane (2×) and the combined organic extracts dried and evaporated. The residue was chromatographed, eluting with methanol/dichloromethane to give firstly the partially purified title compound (0.84 g, 21%) then 1,1-dimethylethyl {(3R,4S)-1-[(3-chloro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-3-hydroxy-4-piperidinyl}carbamate (3.93 g, 48%). The partially purified title compound (0.84 g) was further purified by chromatography eluting with methanol/dichloromethane affording pure product (0.57 g).

1. washAfter 2.5 days the mixture was washed with saturated aqueous sodium bicarbonate solution
2. extractionThe aqueous phase was extracted with dichloromethane (2×)
3. customthe combined organic extracts dried
4. customevaporated
5. customThe residue was chromatographed
6. washeluting with methanol/dichloromethane
7. customto give firstly the
8. custompartially purified title compound (0.84 g, 21%)
9. customThe partially purified title compound (0.84 g)
10. customwas further purified by chromatography
11. washeluting with methanol/dichloromethane affording pure product (0.57 g)