反应详情

A mixture of 4-({3-[8-(methylamino)-3-azabicyclo[3.2.1]oct-3-yl]propyl}amino)benzonitrile (Preparation G; 74.6 mg, 0.25 mmol) and ethyl chloroformate (29.8 mg, 0.27 mmol) in DMF (2.5 mL) was stirred at rt for 24 h. Mass spectroscopic analysis showed that the amine starting material had not been totally consumed, and so additional ethyl chloroformate (50 μL) was added. The mixture was stirred overnight, after which time it was concentrated in vacuo. The resulting residue was dissolved in a mixture of DCM (0.5 mL) and MeCN (2 mL). K2CO3 (100 mg, 0.7 mmol) was added and the mixture stirred for 4 h. Filtration of the mixture and evaporation of the filtrate gave a residue that was dissolved in CHCl3 (1 mL). The solution was filtered through an ion-exchange solid-phase extraction plug (CBA, 2 g). The source flask was washed with additional CHCl3 (0.75 mL), which was then added to the extraction plug, and eluted as fraction 1. The plug was then eluted with CHCl3:MeOH:TEA (8:1:1; 4×2 mL) to give further fractions that were found not to contain any product. Fraction 1 was then added to a silica plug, which was eluted with CHCl3:MeCN (4:1; 3×2.5 mL). Evaporation of the fractions collected gave 79.6 mg (85.9%) of the title compound.

1. customhad not been totally consumed
2. additionso additional ethyl chloroformate (50 μL) was added
3. stirringThe mixture was stirred overnight
4. concentrationafter which time it was concentrated in vacuo
5. dissolutionThe resulting residue was dissolved in a mixture of DCM (0.5 mL) and MeCN (2 mL)
6. stirringthe mixture stirred for 4 h
7. filtrationFiltration of the mixture and evaporation of the filtrate
8. customgave a residue that
9. filtrationThe solution was filtered through an ion-exchange solid-phase extraction plug (CBA, 2 g)
10. washThe source flask was washed with additional CHCl3 (0.75 mL), which
11. additionwas then added to the extraction plug
12. washeluted as fraction 1
13. washThe plug was then eluted with CHCl3:MeOH:TEA (8:1:1; 4×2 mL)
14. customto give further fractions that
15. additionFraction 1 was then added to a silica plug, which
16. washwas eluted with CHCl3:MeCN (4:1; 3×2.5 mL)
17. customEvaporation of the fractions
18. customcollected