反应详情

温度

0 °C

1-Amino-3-(N-methyl-N'-piperazinyl)benzene (197 mg) in anhydrous tetrahydrofuran (30 ml) was cooled to 0° C. whereupon triphosgene (101 mg) was added. The mixture was stirred at 0° C. for 2 min, then triethylamine (430 μl) was added portionwise until pH8. The mixture was then stirred for a further 5 min, allowed to warm to 15° C., and then re-cooled to 0° C. Then a solution 3-amino-5-cycloheptyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (200 mg) (Enantiomer A) in anhydrous tetrahydrofuran (10 ml) was added dropwise over 5 min. The mixture was stirred at 0° C. for 5 min, allowed to warm to room temperature and then stirred for a further 15 min. The undissolved material was removed by filtration. The filtrate was evaporated in vacuo and the residue partitioned between ethyl acetate (50 ml) and water (30 ml). The organic phase was separated, dried (Na2SO4) and evaporated. The residue was chromatographed on silica gel with dichloromethane:methanol (9:1) as eluant to afford the title compound (239 mg) as a colourless solid. Mp 160° C. (dec.). 1H NMR (250 MHz, D6-DMSO) δ 1.05-1.87 (11H, m), 1.88-2.04 (1H, m) 2.21 (3H, s), 2.36-2.47 (4H, m), 2.95-3.21 (5H, m), 3.36 (3H, s), 5.05 (1H, d, J=8 Hz), 6.50 (1H, dd, J=8.2 and 2.0 Hz), 6.61 (1H, d, J=8 Hz), 7.04 (1H, t, J=7.5 Hz), 7.13 (1H, s), 7.25 (1H, d, J=7.5 Hz), 7.39 (1H, t, J=7.0 Hz), 7.52-7.70 (2H, m), 7.76 (1H, d, J=8.0 Hz), 8.89 (1H, s).

1. additionwas added
2. stirringThe mixture was then stirred for a further 5 min
3. temperatureto warm to 15° C.
4. temperaturere-cooled to 0° C
5. stirringThe mixture was stirred at 0° C. for 5 min
6. temperatureto warm to room temperature
7. stirringstirred for a further 15 min
8. customThe undissolved material was removed by filtration
9. customThe filtrate was evaporated in vacuo
10. customthe residue partitioned between ethyl acetate (50 ml) and water (30 ml)
11. customThe organic phase was separated
12. dry with materialdried (Na2SO4)
13. customevaporated
14. customThe residue was chromatographed on silica gel with dichloromethane:methanol (9:1) as eluant