反应详情

To a suspension of sodium hydride (0.035 g of a 60% dispersion in mineral oil) in dry N,N-dimethylformamide (5 ml) was added dropwise a solution of (3RS)-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (0.293 g) in dry N,N-dimethylformamide (2 ml) under stirring at cooling in an ice-bath. After completion of the addition, the mixture was allowed to stand to room temperature and stirred for 2 hours. To the the mixture was added sodium iodide (0.129 g) and followed dropwise a solution of N-chloromethylcarbonyl-2-azatricyclo-[4.3.1.14,8 ]undecane (0.215 g) in dry N,N-dimethylformamide (2 ml) under stirring at cooing in an ice-bath for 1 hour and then at room temperature overnight. The reaction mixture was concentrated in vacuo. The residue was treated with ethyl acetate and water. The organic layer was washed with water and dried over sodium sulfate. Removal of the solvent gave (3RS)-1-[(2-azatricyclo[4.3.1.14,8 ]undec-2-yl)carbonylmethyl]-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (0.537 g), which was used in a following reaction step without further purification.

1. temperatureat cooling in an ice-bath
2. additionAfter completion of the addition
3. customto stand to room temperature
4. stirringstirred for 2 hours
5. stirringunder stirring
6. customat room temperature
7. customovernight
8. concentrationThe reaction mixture was concentrated in vacuo
9. additionThe residue was treated with ethyl acetate and water
10. washThe organic layer was washed with water
11. dry with materialdried over sodium sulfate
12. customRemoval of the solvent