反应详情

To a solution of {6-fluoro-5-[2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzylcarbamoyl]-2-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl}acetic acid from Example 2 (170 mg, 0.30 mmol) in THF (6 ml) were added N-methylmorpholine (47 μl, 0.43 mmol) and isobutyl chlroroformate (57 μl, 0.43 mmol) while cooling in an ice/water bath. The mixture was stirred for 1 h, filtered and added to a solution of sodium borohydride (27 mg, 0.70 mmol) in water (1.5 ml) while cooling in an ice/water bath. The mixture was allowed to warm to room temperature slowly and stirred for 2 h. Saturated ammonium chloride solution (2 ml) was added and the mixture evaporated in vacuo. The residue was partitioned between choroform and water and the organic layer was washed with brine, dried over magnesium sulphate and evaporated in vacuo. The residue was purified by flash chromatography on silica (eluant methanol:dichloromethane 6:94) to give a white solid; yield 104 mg, 64%.

1. temperaturewhile cooling in an ice/water bath
2. filtrationfiltered
3. temperaturewhile cooling in an ice/water bath
4. stirringstirred for 2 h
5. customthe mixture evaporated in vacuo
6. customThe residue was partitioned between choroform and water
7. washthe organic layer was washed with brine
8. dry with materialdried over magnesium sulphate
9. customevaporated in vacuo
10. customThe residue was purified by flash chromatography on silica (eluant methanol:dichloromethane 6:94)
11. customto give a white solid